A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of Clemizole Hydrochloride as Adjunctive Therapy in Patients with Lennox-Gastaut Syndrome

Trial ID: 2025-522552-20-00
Protocol: EPX-100-003
Sponsor: Epygenix Therapeutics Inc.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendors

Diseases & Conditions

Lennox-Gastaut syndrome

Objectives

The primary objective is to evaluate the efficacy of clemizole hydrochloride compared to placebo in patients with Lennox-Gastaut syndrome. The secondary objectives include:

Further assessment of the efficacy of clemizole hydrochloride compared to placebo.
Evaluation of the safety and tolerability of clemizole hydrochloride relative to placebo.

Trial scope: 5, 4, 6.

Participants

This clinical trial involves 162 participants diagnosed with Lennox-Gastaut Syndrome. The study population includes both males and females ranging from 2 to 55 years of age. Eligible participants must demonstrate evidence of major motor seizures, specific electroencephalogram patterns, abnormal cognitive development, and seizure onset at age 11 or younger. Inclusion requires a history of a specific number of monthly seizures, including tonic or tonic/atonic seizures, and insufficient control despite trials of one or more antiseizure medications. Participants must maintain a stable regimen of four or fewer medications for at least 30 days. A ketogenic diet or modified version is permitted if it has been maintained at a steady state for at least four weeks prior to screening. Those with a surgically implanted vagal nerve stimulator are eligible provided the device has been in place for at least six months with stable settings. The population includes individuals of childbearing potential who must utilize medically acceptable birth control methods. All diagnoses are subject to confirmation by an Independent Diagnostic Reviewer.

Plans and Procedures

This multicenter, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of clemizole hydrochloride as an adjunctive therapy in patients diagnosed with Lennox-Gastaut Syndrome. The study utilizes an oral solution administered to either the test group or a placebo group. The research methodology includes a screening visit to confirm diagnosis through clinical history, electroencephalogram review, and approval by an independent diagnostic reviewer. Following screening, participants proceed to a randomization visit. The trial consists of a double-blind phase, which encompasses both a titration and a maintenance phase, followed by an open-label extension phase. The primary endpoint is the percent change in the Clinical Monthly Seizure Measure (CMMS-28) from the baseline period through the end of the double-blind period. Study procedures require the maintenance of a daily seizure diary. Participants may be required to maintain a stable regimen of antiseizure medications and specific dietary protocols, such as a ketogenic diet, throughout the study. Early termination may occur based on investigator judgment or protocol deviations.

Treatment

The experimental medication consists of clemizole hydrochloride administered as an oral solution. The investigational substance is provided for oral administration at a dosage of 00 mg.

The control group receives a placebo, which is a Clemizole Hydrochloride placebo used for comparison in this study involving patients with Lennox-Gastaut Syndrome.

Efficacy

The efficacy of clemizole hydrochloride in patients with Lennox-Gastaut Syndrome will be evaluated using several parameters. The primary endpoint is the percent change in the Clinical Modified Marches Scale (CMMS-28) from the baseline period through the end of the double-blind period, which encompasses both the titration and maintenance phases.

Secondary efficacy assessments include:

The proportion of participants achieving a reduction of 50% or greater in the CMMS-28 from baseline to the end of the double-blind period.
The percent change in seizure-free days as measured by the CMMS-28 from baseline to the end of the double-blind period.
The Clinical Global Impressions-Clinical Change (CGI-C) score at the end of the double-blind period.
The Clinician Assessment of Clinical Global Impressions-Clinical Change (CaGI-C) score at the end of the double-blind period.
The CaGI-CSID score at the end of the double-blind period.
The change in the QI-disability score from baseline to the end of the double-blind period.
The percent change per 28 days in the number of seizure-free days for all seizure types from baseline to the end of the double-blind period.
The percent change in the CMMS-28 from baseline to the end of the double-blind maintenance phase only.
The proportion of participants achieving a reduction of 50% or greater in the CMMS-28 from baseline to the end of the double-blind maintenance phase only.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Males or females, ages ≥2 to ≤55 years, at the time of Screening.
Participant/parent/legal authorized representative (LAR) willing and able to give written informed consent/assent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures. If the participant is not qualified or able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent/LAR must provide appropriate consent for study participation.
Diagnosis of LGS, including: • Evidence of at least one type of countable major motor seizure. • History of electroencephalogram consistent with LGS (abnormal background activity, slow spike-wave discharges [<2.5 Hz], or paroxysmal fast activity during sleep). • Abnormal cognitive development. • Onset of seizures at 11 years of age or younger.
Have a history of at least required number of countable seizures per month in the 2 months prior to Screening that must include tonic or tonic/atonic seizures.
Have at least required number of countable major motor seizures following the Screening Visit.
Approval for participation by the Independent Diagnostic Reviewer at The Epilepsy Consortium after review of the DERF and supporting documentation, such as the Participant Seizure and Medication Diary, EEGs, and neuroimaging. The Independent Reviewer from The Epilepsy Consortium will confirm LGS diagnosis and approve participation of each participant.
If participant has a surgically implanted vagal nerve stimulator: • The vagal nerve stimulator must have been placed ≥6 months prior to the Screening Visit. • The settings must have remained constant for 3 months prior to the Screening Visit and are expected to remain constant throughout the double-blind phase. During the OLE phase, once therapeutic doses have been fully established (Visit 16 onwards), settings can be changed if deemed necessary by the PI, after discussion with the Medical Monitor. • The battery must be expected to last for the duration of the double-blind phase.
Lack of seizure control despite appropriate trial of 1 or more antiseizure medications (ASMs) at therapeutic doses and for adequate duration of treatment per PI judgement.
Stable regimen of 4 or fewer ASMs ≥30 days prior to Visit 1 without a foreseeable dose adjustment for the duration of the study and in generally good health. Minor dose adjustments for tolerability may be permitted after discussion with the Medical Monitor.
Participant, parent, caregiver, or LAR is able and willing to maintain an accurate and complete daily seizure diary.
Willingness and ability to take study drug (suspension) as directed.
Sexually active 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 are listed in Appendix 11. In participants who are not sexually active, abstinence is an acceptable form of birth control and pregnancy testing will be conducted per protocol. Women who are of nonchildbearing potential (i.e., postmenopause or surgical menopause) must have this condition captured in their medical history. Pregnant women are excluded from this study
Ketogenic diet, or a modified version of this diet, is allowed as long as the diet has been initiated and maintained at a steady state for at least 4 weeks prior to Screening and remains stable throughout the double-blind phase. Ketogenic diet does not count as an anti-seizure medication. During the OLE phase, once therapeutic doses have been fully established (Visit 16 onwards), diet can be changed if deemed necessary by the PI after discussion with the Medical Monitor.

cancel

Exclusion Criteria

Has a known sensitivity, allergy, or previous exposure to clemizole HCl.
Concomitant 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 as indicated by any of the following: • Mild or greater aortic regurgitation or moderate or greater mitral regurgitation. • 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 >35 mmHg.
A positive result on drug screen for tetrahydrocannabinol (THC) at Visit 1 (Screening).
Concomitant use of THC/non-prescription cannabidiol preparations.
Does not agree to refraining from intake of grapefruits or grapefruit juice or Seville oranges.
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.
Based on the judgment of the investigator, is unsuitable for the study for any reason, including but not limited to unstable or uncontrolled medical conditions (including psychiatric and neurological conditions) or a medical condition that might interfere with the conduct of the study, confound interpretation of study results, pose a health risk to the participant or compromise the integrity of the study.
Has a significant risk of committing suicide based on history, routine psychiatric examination, investigator’s judgment, or answering “yes” to Question 4 or 5 on the C‑SSRS (over the past 3 months prior to the first dose) or with any suicidal behavior (i.e., answering “yes” to the suicidal behavior questions) in the last 6 months before Screening.
Has moderate or severe hepatic impairment. Asymptomatic participants with mild hepatic impairment (elevated liver enzymes [AST or ALT] <3x ULN or elevated bilirubin <2x ULN) may be entered into the study after review and approval by the Medical Monitor after consideration of comorbidities and concomitant medications.
Has a QT interval corrected using Fridericia’s formula (QTcF) with a mean value of >450 msec (QTcF = QT/3√ RR) at Screening based on the mean of triplicate 12-lead electrocardiograms (ECGs).
Has a known history of long QT syndrome or any significant history of a serious abnormality of the ECG (e.g., recent myocardial infarction, clinically significant arrhythmia).
Has a family history of sudden cardiac death, unexplained death, or death from a primary dysrhythmia potentially associated with QT prolongation in any family member.
Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or progressive CNS 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.
Changes in any chronic medications within the 30 days prior to Screening. All chronic concomitant medications must be relatively stable in dose for at least 30 days prior to the Screening Visit unless otherwise noted. Participants who have minor dose adjustments to manage tolerability may be permitted after discussion with the Medical Monitor.
Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
Concomitant use of drugs that are moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A4 is prohibited. Additionally, concomitant use of drugs with a narrow therapeutic index that are sensitive substrates for CYP3A4, CYP2C19, CYP2B6, CYP2D6, CYP2C8, and various transporters is prohibited.
Prior or concomitant use of lorcaserin.
Concomitant use of any prohibited drug listed in Protocol Appendix 1

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Not Yet Recruiting	20 May 2026	12
Hungary	Not Yet Recruiting	20 May 2026	12
Italy	Recruiting	20 May 2026	25
Poland	Recruiting	20 May 2026	12
Romania	Recruiting	20 May 2026	12
Spain	Recruiting	20 May 2026	25