search
Back to results

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

Primary Purpose

Epilepsy

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
EQU-001
Sponsored by
Equilibre Biopharmaceuticals B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy, Seizure, Adult

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

      -

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.

Sites / Locations

  • Consultants in Epilepsy and Neurology PLLC
  • Mid-Atlantic Epilepsy and Sleep Center
  • Northeast Regional Epilepsy Group
  • NYU Langone Medical Center, NYU Comprehensive Epilepsy Center
  • Comprehensive Epilepsy Center at Thomas Jefferson University
  • University of Virginia
  • Hadassah Medical Center
  • Rabin Medical Center
  • Chaim Sheba Medical center
  • Tel Aviv Sourasky Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Study drug EQU-001

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in C-SSRS responses as compared with baseline in treatment cohort as compared with placebo.
Median change in the number of countable seizures overall and by seizure type (focal, generalized, and unknown onset).
Median change in the number of generalized tonic-clonic and focal to generalized tonic-clonic seizures.
Percent (%) of subjects who are seizure free.
Number of subjects who withdraw from treatment because of study-drug effects.
Number of subjects in each dose cohort who decrease their dose of study drug because of treatment-related effects.
Correlation of plasma levels of EQU-001 with % seizure reduction
Correlation of plasma levels of biomarkers with % seizure reduction
Seizure freedom in treated subjects overall and at each dose as compared with placebo.
Change in the Quality of Life in Epilepsy-31-P (QOLIE-31-P) scale score as compared with baseline in treatment cohort as compared with placebo.
Maximum score: 100, Minimum score: 0, Higher scores reflect better quality of life, lower scores reflect lower quality of life.

Full Information

First Posted
September 22, 2021
Last Updated
May 11, 2023
Sponsor
Equilibre Biopharmaceuticals B.V.
search

1. Study Identification

Unique Protocol Identification Number
NCT05063877
Brief Title
Safety, Tolerability, and Exploratory Efficacy of Adjunctive EQU-001 for Seizures in Adults With Epilepsy
Official Title
A Dose-Ranging Safety, Tolerability, and Exploratory Efficacy Study of Adjunctive EQU-001 for Seizures in Adults With Epilepsy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 31, 2021 (Actual)
Primary Completion Date
October 11, 2022 (Actual)
Study Completion Date
October 11, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Equilibre Biopharmaceuticals B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
Detailed Description
EQU-201 is a Phase 2 randomized, double-blind, placebo-controlled study to evaluate dose-ranging safety, tolerability, and exploratory efficacy of adjunctive EQU-001 using the continuous reassessment method (CRM). 10 participants diagnosed with epilepsy according to the International League Against Epilepsy (ILAE) Classification of the Epilepsies 2017 criteria whose seizures are uncontrolled on one to four concomitant antiepileptic drugs (AEDs) for ≥4 weeks will be enrolled in 4 dose cohorts (10 mg, 20 mg, 40 mg, 60 mg) The participants will be randomized 4:1, drug to placebo. The dosing is for 12 weeks, after which, safety data will be reviewed post 14 days to determine whether the next cohort can be opened. Once the 12-week study dosing period is complete, all subjects may enroll in an open-label extension, during which period investigators may make dose adjustments down to 20 mg and up 80 mg. This study of EQU-001 will provide safety of a range of doses, tolerability, and PK data in patients with epilepsy and aims to identify drug-specific DLTs and MTD. The PK component will characterize the PK of EQU-001 to inform dosing and may help to correlate exposures with any DLTs or other treatment-related AEs. The open label extension component will provide data on subject safety, tolerability and efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Epilepsy, Seizure, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
4:1 treatment to placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Arm Title
Study drug EQU-001
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Intervention Type
Drug
Intervention Name(s)
EQU-001
Intervention Description
EQU-001 in 10 mg and 20 mg capsules
Primary Outcome Measure Information:
Title
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.
Time Frame
Upto 84 days
Secondary Outcome Measure Information:
Title
Change in C-SSRS responses as compared with baseline in treatment cohort as compared with placebo.
Time Frame
Day 84
Title
Median change in the number of countable seizures overall and by seizure type (focal, generalized, and unknown onset).
Time Frame
Day 14, 42, 70, 98
Title
Median change in the number of generalized tonic-clonic and focal to generalized tonic-clonic seizures.
Time Frame
Day 14, 42, 70, 98
Title
Percent (%) of subjects who are seizure free.
Time Frame
Day 1 upto day 84
Title
Number of subjects who withdraw from treatment because of study-drug effects.
Time Frame
Upto 14 days
Title
Number of subjects in each dose cohort who decrease their dose of study drug because of treatment-related effects.
Time Frame
Upto 14 days
Title
Correlation of plasma levels of EQU-001 with % seizure reduction
Time Frame
Weeks 2, 4, 8, 12
Title
Correlation of plasma levels of biomarkers with % seizure reduction
Time Frame
Weeks 4, 8, 12
Title
Seizure freedom in treated subjects overall and at each dose as compared with placebo.
Time Frame
Weeks 3 to 12 and Weeks 1 to 12 relative to the baseline observation period
Title
Change in the Quality of Life in Epilepsy-31-P (QOLIE-31-P) scale score as compared with baseline in treatment cohort as compared with placebo.
Description
Maximum score: 100, Minimum score: 0, Higher scores reflect better quality of life, lower scores reflect lower quality of life.
Time Frame
Day 84

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. - Exclusion Criteria: 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. Receiving felbamate for <1 year prior to screening Receiving vigabatrin for <2 years prior to screening. Subjects on vigabatrin should have available, appropriate documentation of visual fields Receiving ezogabine (ex-US) at screening Use of the following medications and foods at screening or baseline that may interfere with study drug: CYP3A4 inducers: rifampin, lumacaftor, mitotane, enzalutamide, apalutamide, St. John's wort, glucocorticoids 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, pomegranate and pomegranate juice Additional medications that may interact with CYP3A4, PGP, or Vitamin K: fluconazole, isavuconazole, cyclosporine, amiodarone, dronaderone, verapamil, imatinib, warfarin, acenocoumarol Has any of the following laboratory abnormalities at screening: Positive COVID test Positive urine drug screen (except as clinically indicated) Total bilirubin or higher ≥1.5× the site laboratory upper limit of normal (ULN) ALT or ALT ≥2× the site laboratory ULN HbA1c >7.0% Positive hCG (female participants) (screening or baseline) Subject is not approved for study inclusion by the Epilepsy Consortium based on the diagnostic review form Any condition that, in the opinion of the investigator, may impact a subject's safety or ability to follow study procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ya-El Mandel-Portnoy, PhD
Organizational Affiliation
Equilibre
Official's Role
Study Director
Facility Information:
Facility Name
Consultants in Epilepsy and Neurology PLLC
City
Boise
State/Province
Idaho
ZIP/Postal Code
83702
Country
United States
Facility Name
Mid-Atlantic Epilepsy and Sleep Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Northeast Regional Epilepsy Group
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
NYU Langone Medical Center, NYU Comprehensive Epilepsy Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Comprehensive Epilepsy Center at Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Rabin Medical Center
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Chaim Sheba Medical center
City
Ramat Gan
ZIP/Postal Code
5262000
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs