EpilepsyPhase 2NCT05063877
Safety, Tolerability, and Exploratory Efficacy of Adjunctive EQU-001 for Seizures in Adults With Epilepsy
A Phase 2 study testing EQU-001 in people with Epilepsy, run by Equilibre Biopharmaceuticals B.V. at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Epilepsy
- What is being tested?
- EQU-001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 31 Aug 2021to 11 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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.
- -
Who cannot join
- 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
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- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States6 sites
Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
Consultants in Epilepsy and Neurology PLLC
Boise, Idaho, 83702
University of Virginia
Charlottesville, Virginia, 22903
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
NYU Langone Medical Center, NYU Comprehensive Epilepsy Center
New York, New York, 10016
Comprehensive Epilepsy Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Israel4 sites
Hadassah Medical Center
Jerusalem, 9112001
Rabin Medical Center
Petah Tikva, 4941492
Chaim Sheba Medical center
Ramat Gan, 5262000
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906
About this study
Official title: A Dose-Ranging Safety, Tolerability, and Exploratory Efficacy Study of Adjunctive EQU-001 for Seizures in Adults With Epilepsy
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.
Read the 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.
- Conditions
- Epilepsy
- Being tested
- Placebo, EQU-001
- Keywords
- Epilepsy, Seizure, Adult
- Medical subject headings
- Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matched placebo
EQU-001Drug
EQU-001 in 10 mg and 20 mg capsules
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: EQU-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Upto 84 days
Secondary outcomes (10)
Change in C-SSRS responses as compared with baseline in treatment cohort as compared with placebo.
Measured: Day 84
Median change in the number of countable seizures overall and by seizure type (focal, generalized, and unknown onset).
Measured: Day 14, 42, 70, 98
Median change in the number of generalized tonic-clonic and focal to generalized tonic-clonic seizures.
Measured: Day 14, 42, 70, 98
Percent (%) of subjects who are seizure free.
Measured: Day 1 upto day 84
Number of subjects who withdraw from treatment because of study-drug effects.
Measured: Upto 14 days
Number of subjects in each dose cohort who decrease their dose of study drug because of treatment-related effects.
Measured: Upto 14 days
Correlation of plasma levels of EQU-001 with % seizure reduction
Measured: Weeks 2, 4, 8, 12
Correlation of plasma levels of biomarkers with % seizure reduction
Measured: Weeks 4, 8, 12
Seizure freedom in treated subjects overall and at each dose as compared with placebo.
Measured: Weeks 3 to 12 and Weeks 1 to 12 relative to the baseline observation period
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.
Measured: Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study start31 Aug 2021
- Primary completion11 Oct 2022
- Study completion11 Oct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- 4:1 treatment to placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Equilibre Biopharmaceuticals B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ya-El Mandel-Portnoy, PhD, Study director, Equilibre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063877
- Sponsor's protocol ID
- EQU-201
- Status last verified
- May 2023
- First submitted
- 22 Sep 2021
- Last updated
- 15 May 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose-Ranging Safety, Tolerability, and Exploratory Efficacy Study of Adjunctive EQU-001 for Seizures in Adults With Epilepsy
- ClinicalTrials.gov ID
- NCT05063877
- Acronym / sponsor ID
- EQU-201
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Seizure, Adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Equilibre Biopharmaceuticals B.V.Industry (pharma, biotech, devices)
- Study start
- 31 Aug 2021 (actual)
- Primary completion
- 11 Oct 2022 (actual)
- Study completion
- 11 Oct 2023 (estimated)
- First posted
- 1 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 4:1 treatment to placebo
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMatched 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 |
| Study drug EQU-001 | Experimental | Drug: EQU-00110mg 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (31 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatched placebo | Drug | Placebo |
| EQU-001EQU-001 in 10 mg and 20 mg capsules | Drug | Study drug EQU-001 |
Primary outcome
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
10 secondary outcomes
Change in C-SSRS responses as compared with baseline in treatment cohort as compared with placebo.
Time frame: Day 84
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
Median change in the number of generalized tonic-clonic and focal to generalized tonic-clonic seizures.
Time frame: Day 14, 42, 70, 98
Percent (%) of subjects who are seizure free.
Time frame: Day 1 upto day 84
Number of subjects who withdraw from treatment because of study-drug effects.
Time frame: Upto 14 days
Number of subjects in each dose cohort who decrease their dose of study drug because of treatment-related effects.
Time frame: Upto 14 days
Correlation of plasma levels of EQU-001 with % seizure reduction
Time frame: Weeks 2, 4, 8, 12
Correlation of plasma levels of biomarkers with % seizure reduction
Time frame: Weeks 4, 8, 12
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
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.
Time frame: Day 84
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ya-El Mandel-Portnoy, PhD study director
Equilibre
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EQU-001 in people with Epilepsy, run by Equilibre Biopharmaceuticals B.V. at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023.