Study of EQU-001 for Uncontrolled Focal Onset Seizures

NCT05473442 | Terminated Phase 2 FDA Drug

• 1 other identifier: EQU-202
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 13

Brief 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.

Conditions

Focal Onset Seizures

Keywords

EQU-001; Epilepsy; Seizures; Focal; Phase II

Outcome Measures

Primary Outcomes (1)

• Median percentage change in the overall number of countable observable seizures

  per 28-day period relative to baseline in each treatment arm during the double-blind treatment period compared with placebo.

  Every 4 weeks from week 1 up to week 16

Secondary Outcomes (12)

• Median percentage change in the overall number of countable observable seizures

  Every 4 weeks from week 5 up to week 16

• ≥ 50% responder rates

  Week 1 to 16

• ≥ 50% responder rates

  Week 5 to 16

• Difference in PGI-C Scale: Patient's Global Impression of Change (PGIC)

  Week 6 to 16

• Median percentage change in the number of countable observable seizures by subtype

  Week 1 to 16

Study Arms (3)

EQU-001 60 mg

EXPERIMENTAL

EQU-001 60 mg (3 x 20 mg pills)

Drug: EQU-001

EQU-001 20 mg

EXPERIMENTAL

EQU-001 20 mg (1 x 20 mg pill + 2 x matching placebo pills)

Drug: EQU-001; Other: Matching Placebo

EQU-001 0 mg

PLACEBO COMPARATOR

EQU-001 0 mg (3 x matching placebo pills)

Other: Matching Placebo

Interventions

EQU-001 DRUG

20 mg pills of EQU-001

EQU-001 20 mg; EQU-001 60 mg

Matching Placebo OTHER

20 mg matching placebo pills

EQU-001 0 mg; EQU-001 20 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18- 65 years at time of informed consent
• 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.
• 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.
• Subject has no seizures that are not focal by the ILAE 2017 criteria
• 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.
• 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.
• Seizures uncontrolled after an adequate trial of at least 1 ASM within the last 2 years.
• 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.
• 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.
• Females of childbearing potential who are not sexually inactive (abstinent) for 30 days prior to the first dose, throughout the study, and then for 30 days following the last dose, must agree to use of one of the following acceptable birth control methods from 30 days prior to the first dose through 30 days after the last dose of study drug:
• i. Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) together with a condom or other barrier method ii. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) together with a condom or other barrier method iii. Intrauterine device (IUD) together with a condom or other barrier method iv. Intrauterine hormone releasing system (IUS) together with a condom or other barrier method v. Bilateral tubal occlusion, hysterectomy, bilateral oophorectomy vi. Vasectomized partner (vasectomy \>6 months ago)
• For this study, pre-menopausal is defined as not meeting the clinical criteria for post menopausal, that is, no menstrual period for at least one year, in the absence of other identifiable cause(s) of not having a period, together with the absence of typical symptoms of menopause, such as hot flashes and mood instability. True abstinence is allowable when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

You may not qualify if:

• Pregnant or lactating
• History of hypersensitivity to ivermectin or to any of the excipients in the EQU-001 gelcap
• History of status epilepticus in the past 1 year from screening
• History of pseudo- or nonepileptic seizures, or other nonepileptic events that could be confused with epileptic seizures, within the past 5 years
• History of traumatic brain injury within 30 days prior to screening
• Resective epilepsy surgery within 1 year; epilepsy-related radiosurgery within 2 years or Ventriculoperitoneal shunt placement within 1 year
• 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.
• 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
• 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
• History of substance use disorder, including alcohol, within the past 2 years
• Currently in another investigational drug study
• 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.
• 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.
• Currently taking retigabine/ezogabine
• 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 If a subject is taking benzodiazepines for an indication other than epilepsy (e.g., anxiety, sleep), the dose should to be stable for at least 4 weeks prior to screening and remain stable throughout screening and double blind periods of the study.

Sponsors & Collaborators

• Equilibre Biopharmaceuticals B.V.: lead

Study Sites (13)

Consultants in Epilepsy and Neurology, PLLC

Boise, Idaho, 83702, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Institute of Neurology and Neurosurgery at Saint Barnabas

Livingston, New Jersey, 07039, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Sooner Clinical Research, Inc.

Oklahoma City, Oklahoma, 73112, United States

Location

Comprehensive Epilepsy Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Northwest Houston Neurology

Cypress, Texas, 77429, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Ramban Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical center

Ramat Gan, 5262000, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

MeSH Terms

Conditions

Seizures; Epilepsy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled, randomized at a 1:1:1 ratio to receive 20 mg of EQU-001, 60 mg of EQU-001 or a matched placebo

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 26, 2022
• Study Start: December 27, 2022
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

US (8); IL (5)