Study of EQU-001 for Uncontrolled Focal Onset Seizures

• Status: Not yet recruiting
• Trial end date: 2026-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a Phase 2 multinational, double-blind, placebo-controlled, randomized (1:1:1), efficacy and safety study of adjunctive EQU-001 for the treatment of focal onset seizures in subjects aged 18 to 65 years, who have been diagnosed with epilepsy according to International League Against Epilepsy (ILAE) Classification of the Epilepsies 2017 criteria This study is designed to test the efficacy and safety of EQU-001 20 mg and 60 mg as compared with placebo as an add-on anti-seizure medication (ASM) in subjects with uncontrolled focal onset seizures.

The treatment portion of the study will be comprised of a 4-week double-blind medication activation period and a 12-week double-blind maintenance period.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Equilibre Biopharmaceuticals B.V.

Criteria

Inclusion Criteria:

1. Age 18- 65 years at time of informed consent

2. The subject or designee is willing and able to keep an accurate study diary, the subject is able to adhere to the protocol, the subject or the subject's legal representative is able read, understand, and sign informed consent, as applicable.

3. Diagnosed with focal epilepsy according to ILAE (2017) criteria. Diagnosis to include clinical history and an EEG consistent with focal epilepsy. A normal interictal EEG is allowed when the clinical history is consistent with focal epilepsy.

4. Subject has no seizures that are not focal by the ILAE 2017 criteria

5. Subject must have 8 countable, observable focal seizures during the 8-week baseline period prior to randomization, including at least 3 in each 4-week period with no 21-day seizure-free period. These seizures must be observable (focal aware with motor component, focal impaired awareness, focal to bilateral tonic-clonic) and as such may not include focal aware seizures without a detectable motor component, aphasia, or other observable symptom.

6. Must have had a brain MRI or contrast-enhanced head CT scan with an available report (images need not be available) that has been performed within the past 10 years and that is negative for confounding conditions such as tumor, infection, demyelinating disease, or other progressive neurological disease. Remote stroke that may represent the etiology for epilepsy is allowed. If no such CT or MRI report is available, a potential subject will be asked to undergo a head CT scan with intravenous contrast to meet eligibility criteria prior to study enrollment.

7. Seizures uncontrolled after an adequate trial of at least 1 ASM within the last 2 years.

8. Currently receiving treatment with 1-3 ASMs with doses stable for at least 4 weeks prior to screening. These medications must stay stable during the 8-week baseline period and during the 16-week treatment period. In the case that the plasma level of a concomitant ASM changes, the subject and their physician may then modify the dose to maintain the plasma level that was present prior to beginning the study drug. and must document the change in the EDC system.

9. If participant has a vagal nerve stimulator (VNS), responsive neurostimulator (RNS) or deep brain stimulator (DBS), it must have been implanted and activated >1 year prior to screening, and stimulation parameters that have been stable for >3 months, and battery life of unit anticipated to extend for duration of trial.

10. Females of childbearing potential who are not sexually inactive (abstinent) for 14 days prior to the first dose, throughout the study, and then for 14 days following the last dose, must agree to use acceptable birth control methods:

Exclusion Criteria:

1. Pregnant or lactating

2. History of hypersensitivity to ivermectin or to any of the excipients in the EQU-001 gelcap

3. History of status epilepticus in the past 1 year from screening

4. History of pseudo- or nonepileptic seizures, or other nonepileptic events that could be confused with epileptic seizures, within the past 5 years

5. History of traumatic brain injury within 30 days prior to screening

6. Resective epilepsy surgery within 1 year; epilepsy-related radiosurgery within 2 years

7. Presence of progressive neurological disorder or other progressive disorder or unstable medical condition(s) that may confound study results. History of long QT syndrome, family history of sudden death of unknown cause.

8. Psychiatric disorder where changes in pharmacotherapy are needed or anticipated during the study or which would interfere with the subject's ability to participate in the trial

9. Active suicidal plan/intent in the past 6 months, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt as evidenced by a positive response to C-SSRS questions 4 or 5

10. History of substance use disorder, including alcohol, within the past 2 years

11. Currently in another investigational drug study

12. Currently on felbamate for less than one year before visit 1 (aplastic anemia and hepatic failure usually occur within 6 months to one year). If on felbamate, documentation of stable hemogram and liver enzyme tests must be present.

13. Currently on vigabatrin for less than 2 years before visit 1, as most visual field changes occur between 6 months and 2 years Subjects on vigabatrin should have available, appropriate documentation of visual fields.

14. Currently taking retigabine/ezogabine

15. History of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1-time rescue) more than once in the 4 weeks prior to the baseline visit or more than once per 4 weeks during the 8-week baseline period

16. Currently taking ivermectin, or has taken it within the last 4 weeks prior to visit 1

17. Has had a COVID-19 vaccination within the past 2 weeks prior to visit 1 (allowable to rescreen or to delay randomization) 18a.Use of the following medications within 4 weeks of the baseline visit and throughout the study that may interfere with study drug metabolism (please note ASMs with CYP3A4 metabolism are not excluded from this study, as drug levels and safety are monitored throughout the study): i. CYP3A4 inducers: rifampin, lumacaftor, mitotane, enzalutamide, apalutamide, St. John's wort, glucocorticoids ii. Medications with PGP interactions: amiodarone, apalutamide, verapamil, lorlatinib, rifampin, St. John's wort 18b. Use of the following medications/foods is not strictly prohibited but is discouraged. Please make every attempt to refrain and to record each incidence of use of any of these (along with all medications and supplements).

ii. CYP3A4 inhibitors, including, but not limited to clarithromycin, ceritinib, idelalisib, lonafarnib, tucatinib, erythromycin, telithromycin, diltiazem, posaconazole, voriconazole, nefazodone, itraconazole, ketoconazole, anti-retroviral drugs (atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), grapefruit and grapefruit juice, pomegranate fruit and pomegranate juice iii. Additional medications that may interact with CYP3A4, PGP, or Vitamin K: fluconazole, isavuconazole, cyclosporine, imatinib, warfarin, acenocoumarol 19. Has any of the following laboratory or exam abnormalities: i. Positive urine drug screen (methamphetamines, amphetamines, cocaine, PCP, opioids, barbiturates) at screening without a therapy related explanation ii. Positive hCG (female participants) (at screening or visit 2/enrollment) iii. QTcF > 450 msec at visit 2/enrollment 20. Subject is not approved for study inclusion by the Epilepsy Consortium based on the diagnostic review form 21. Any condition that, in the opinion of the investigator, may impact a subject's safety or ability to follow study procedures