An Efficacy and Safety Study of Clemizole HCl in Patients with Lennox-Gastaut Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Epygenix Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Epygenix Therapeutics, Inc.

External identifiers

EU CT number

2025-522552-20-00

ClinicalTrials.gov

NCT05066217

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of clemizole HCl compared with placebo

Secondary objectives 3

1. To further evaluate the efficacy of clemizole HCl compared with placebo
2. To further evaluate the efficacy of clemizole HCl compared with placebo
3. To assess the safety and tolerability of clemizole HCl compared with placebo

Conditions and MedDRA coding

Lennox-Gastaut Syndrome

Study design 5 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Males or females, ages ≥2 to ≤55 years, at the time of Screening.
2. 2. 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.
3. 3. 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.
4. 4. 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.
5. 5. Have at least required number of countable major motor seizures following the Screening Visit.
6. 6. 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.
7. 7. 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.
8. 8. 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.
9. 9. 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.
10. 10. Participant, parent, caregiver, or LAR is able and willing to maintain an accurate and complete daily seizure diary.
11. 11. Willingness and ability to take study drug (suspension) as directed.
12. 12. 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
13. 13. 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.

Exclusion criteria 18

1. 1. Has a known sensitivity, allergy, or previous exposure to clemizole HCl.
2. 10. 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.
3. 12. A positive result on drug screen for tetrahydrocannabinol (THC) at Visit 1 (Screening).
4. 13. Concomitant use of THC/non-prescription cannabidiol preparations.
5. 14. Does not agree to refraining from intake of grapefruits or grapefruit juice or Seville oranges.
6. 15. 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.
7. 16. 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.
8. 17. 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.
9. 18. 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.
10. 2. 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).
11. 3. 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).
12. 4. 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.
13. 5. 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.
14. 6. 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.
15. 7. Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
16. 8. 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.
17. 9. Prior or concomitant use of lorcaserin.
18. 11. Concomitant use of any prohibited drug listed in Protocol Appendix 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in CMMS-28 from the Baseline Period through the end of the DB Period (Titration plus Maintenance Phase)

Secondary endpoints 10

1. Proportion of participants with ≥50% reduction in CMMS-28 from the Baseline Period through the end of the DB Period (Titration plus Maintenance Phase)
2. Percent change in CMMS-28 seizure-free days from the Baseline Period through the end of the DB Period (Titration plus Maintenance Phase)
3. CGI-C score at the end of the DB Period (Titration plus Maintenance Phase)
4. CaGI-C score at the end of the DB Period (Titration plus Maintenance Phase)
5. CaGI-CSID score at the end of the DB Period (Titration plus Maintenance Phase)
6. Change in QI-disability score from Baseline to the end of the DB Period (Titration plus Maintenance Phase)
7. 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 (Titration plus Maintenance Phase)
8. Percent change in CMMS-28 from the Baseline Period through the end of the DB Maintenance Phase only
9. Proportion of participants with ≥50% reduction in CMMS-28 from the Baseline Period through the end of the DB Maintenance Phase only
10. Incidence of TEAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Epygenix Therapeutics Inc.

Sponsor organisation

Epygenix Therapeutics Inc.

Address

630 West Germantown Pike Suite 215

City

Plymouth Meeting

Postcode

19462-1069

Country

United States

Scientific contact point

Organisation

Epygenix Therapeutics Inc.

Contact name

Regulatory Affairs Department

Public contact point

Organisation

Epygenix Therapeutics Inc.

Contact name

Regulatory Affairs Department

Third parties 13

Locations

6 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications