Safety, Tolerability, and Exploratory Efficacy of Adjunctive EQU-001 for Seizures in Adults With Epilepsy

• Status: Recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a double-blind, placebo controlled, randomized study of dose-ranging safety, tolerability, exploratory efficacy of adjunctive EQU-001 for seizures using the continuous reassessment method in patients diagnosed with epilepsy.

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

Details

• Lead Sponsor: Equilibre Biopharmaceuticals

Criteria

Inclusion Criteria:

1. Able to provide informed consent, or consent provided by a Legally Authorized Representative (LAR)

2. Diagnosed with epilepsy according to ILAE 2017 criteria and with uncontrolled countable seizures (as per Epilepsy Study Consortium review) on one to four concomitant anti-seizure medicines (AEDs) at optimal stable dosages for at least 4 weeks prior to screening and throughout the treatment period

3. Age 18 to 70 years of age

4. Must have had a brain MRI or CT scan with an available report (images need not be available) that is negative for other confounding conditions

5. Must have an EEG report consistent with the subject's seizure type(s)

6. Pre-menopausal females and males with pre-menopausal sexual partners should either be sexually inactive (abstinent) for 21 days prior to the first dose, throughout the study, and for 14 days following the last dose or, if heterosexually active, agree to use of one of the following acceptable birth control methods for the period above:

1. Intrauterine device (IUD) in place

2. Hormonal contraceptives plus barrier method

3. At least 2 barrier methods (condom, diaphragm) with spermicide

4. Surgical sterilization of participant or partner(s) (bilateral tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy > 6 months ago)

7. Able and willing to adhere to protocol; the subject or selected observer can keep an accurate seizure diary

8. Before progressing from Baseline Period to Randomization:

1. A subject must experience at least 3 countable seizures per 4 weeks prior to randomization, including at least the 4-week baseline period.

2. These seizures may be generalized, focal, or of unknown onset, but may not include absence seizures or focal aware seizures without a detectable motor component, aphasia, or other observable symptom.

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Exclusion Criteria:

1. Pregnant or lactating female

2. History of hypersensitivity to ivermectin

3. Current ivermectin use

4. History of progressive neurological disorder or other significant progressive disorder or unstable medical condition(s)

5. Change in AED regimen in the 28 days prior to screening

6. Taking >4 concomitant AEDs at screening

7. History of status epilepticus in the 2 years prior to screening

8. A vagal nerve stimulator (VNS), responsive neurostimulator (RNS) or deep brain stimulator (DBS), implanted or activated <1 year prior to screening, or with stimulation parameters stable for <3 months or battery life of unit not anticipated to extend for the duration of the trial

9. History of traumatic brain injury within 28 days prior to screening

10. History of psychogenic non-epileptic seizures (PNES), active or within 2 years prior to study entry

11. Epilepsy-related surgery within 1 year prior to screening, epilepsy-related radiosurgery or laser surgery within 1 year prior to screening

12. Epilepsy dietary therapy initiated <3 months prior to screening

13. Psychiatric disorder in which changes in pharmacotherapy are needed or anticipated during the study

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

15. Administration of investigational product in another trial within 28 days prior to the first expected study drug administration, or five half-lives, whichever is longer.

16. Receiving felbamate for <1 year prior to screening

17. Receiving vigabatrin for <2 years prior to screening. Subjects on vigabatrin should have available, appropriate documentation of visual fields

18. Receiving ezogabine (ex-US) at screening

19. Use of the following medications and foods at screening or baseline that may interfere with study drug:

1. CYP3A4 inducers: rifampin, lumacaftor, mitotane, enzalutamide, apalutamide, St. John's wort, glucocorticoids

2. CYP3A4 inhibitors including and not limited to: clarithromycin, ceritinib, idelalisib, lonafarnib, tucatinib, erythromycin, telithromycin, diltiazem, ketoconazole, posaconazole, voriconazole, telithromycin, nefazodone, mifepristone, itraconazole, ketoconazole, anti-retroviral drugs (atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir), grapefruit and grapefruit juice

20. Has any of the following laboratory abnormalities at screening or baseline:

1. Positive COVID test

2. Positive urine drug screen

3. Total bilirubin or higher ≥1.5× the site laboratory upper limit of normal (ULN)

4. ALT or ALT ≥2× the site laboratory ULN

5. HbA1c >6.5%

6. Positive hCG (female participants)

21. Subject is not approved for study inclusion by the Epilepsy Consortium based on the diagnostic review form

22. Any condition that, in the opinion of the investigator, may impact a subject's ability to follow study procedures.