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)

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]

Trial duration

1 Aug 2023 → ongoing

Decision date (initial)

2024-12-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-518628-57-00

EudraCT number

2021-003425-30

ClinicalTrials.gov

NCT00945880

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of EPX-100 compared with placebo as adjunctive therapy in participants with Dravet Syndrome (DS)

Conditions and MedDRA coding

Dravet syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male and female outpatient participants 2 years and older at time of consent. 2. 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, and • Genetic mutation of the SCN1A gene must be documented. 3. The participant must be approved to participate by the PI after review of the medical history, baseline seizure diaries and inclusion/exclusion criteria. The Independent Reviewer will confirm Dravet Syndrome diagnosis for each participant enrolled in the study and adjudicate all seizure types on the seizure diaries. 4. #X countable convulsive seizures with observable motor signs) per 4-week baseline period (Observational Phase). 5. Participants should be on a stable regimen of AEDs #30 days prior to Visit 1 and generally in good health. 6. Parent or LAR is able and willing to maintain an accurate and complete daily seizure calendar. 7. Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control and have a negative urine pregnancy test at the screening visit. AWCBP 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. 8. Have parent or LAR available and willing to give written informed consent, after being properly informed of the nature and risks of the study and prior to engaging in any study- related procedures.

Exclusion criteria 1

1. 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, phenytoin, and/or phenobarbital, 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 fenfluramine or 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The percent change in CMS-28 in the Maintenance Period relative to baseline.

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

Paul Kirsch

Public contact point

Organisation

Epygenix Therapeutics Inc.

Contact name

Paul Kirsch

Locations

3 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 92 files

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

Application history

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