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

NCT05063877 | Unknown Phase 2 FDA Drug

• 1 other identifier: EQU-201
• Study Type: interventional
• Target: 43
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Epilepsy

Keywords

Epilepsy; Seizure; Adult

Outcome Measures

Primary Outcomes (1)

• Comparison of Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0, November 2017, treatment-related adverse events (TRAEs) in each dose cohort as compared with placebo.

  Upto 84 days

Secondary Outcomes (10)

• Change in C-SSRS responses as compared with baseline in treatment cohort as compared with placebo.

  Day 84

• Median change in the number of countable seizures overall and by seizure type (focal, generalized, and unknown onset).

  Day 14, 42, 70, 98

• Median change in the number of generalized tonic-clonic and focal to generalized tonic-clonic seizures.

  Day 14, 42, 70, 98

• Percent (%) of subjects who are seizure free.

  Day 1 upto day 84

• Number of subjects who withdraw from treatment because of study-drug effects.

  Upto 14 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matched placebo control 10 mg capsule or 20 mg capsules totaling to 10 mg, 20 mg, 40mg or 60 mg will be administered once daily orally for 12 weeks with the option for open-label extension. Intervention: Drug: Placebo

Drug: Placebo

Study drug EQU-001

EXPERIMENTAL

10mg capsules or 20 mg EQU-001 capsules totally 10 mg, 20 mg, 40 mg, 60 mg will be administered once orally daily to active-treatment subjects for 12-weeks with the option for open-label extension. During the open-label extension, subjects taking 60 mg dose for 4 weeks or longer may increase to 80 mg per day dose, at the discretion of the PI. Intervention: Drug : EQU-001

Drug: EQU-001

Interventions

Placebo DRUG

Matched placebo

Placebo

EQU-001 DRUG

EQU-001 in 10 mg and 20 mg capsules

Study drug EQU-001

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able to provide informed consent, or consent provided by a Legally Authorized Representative (LAR)
• 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
• Age 18 to 60 years of age
• 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
• Must have an EEG report consistent with the subject's seizure type(s)
• 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:
• Intrauterine device (IUD) in place
• Hormonal contraceptives plus barrier method
• At least 2 barrier methods (condom, diaphragm) with spermicide
• Surgical sterilization of participant or partner(s) (bilateral tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy \> 6 months ago)
• Able and willing to adhere to protocol; the subject or selected observer can keep an accurate seizure diary
• Before progressing from Baseline Period to Randomization:
• A subject must experience at least 3 countable observable seizures per 4 weeks prior to randomization, including at least the 4-week baseline period.
• 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.

You may not qualify if:

• Pregnant or lactating female
• History of hypersensitivity to ivermectin
• Ivermectin use within 28 days of screening
• History of progressive neurological disorder or other significant progressive disorder or unstable medical condition(s)
• Change in AED regimen in the 28 days prior to screening
• Taking \>4 concomitant AEDs at screening
• History of status epilepticus in the 2 years prior to screening
• 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
• History of traumatic brain injury within 28 days prior to screening
• History of psychogenic non-epileptic seizures (PNES), active or within 2 years prior to study entry
• Epilepsy-related surgery within 1 year prior to screening, epilepsy-related radiosurgery or laser surgery within 1 year prior to screening
• Epilepsy dietary therapy initiated \<3 months prior to screening
• Psychiatric disorder in which changes in pharmacotherapy are needed or anticipated during the study
• 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.
• 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.

Sponsors & Collaborators

• Equilibre Biopharmaceuticals B.V.: lead

Study Sites (10)

Consultants in Epilepsy and Neurology PLLC

Boise, Idaho, 83702, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

NYU Langone Medical Center, NYU Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Comprehensive Epilepsy Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

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

Epilepsy; Seizures

Condition Hierarchy (Ancestors)

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

Study Officials

• Ya-El Mandel-Portnoy, PhD

  Equilibre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties are blinded for the initial two week safety period. A sponsor study physician and statistician (not an outcomes assessor) will be unblinded after the initial two week period to monitor ongoing safety, PK and concomitant drug levels
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 4:1 treatment to placebo

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: October 1, 2021
• Study Start: August 31, 2021
• Primary Completion: October 11, 2022
• Study Completion: October 11, 2023
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); IL (4)