Expired Therapeutic exploratory (Phase II) focal (partial onset) epilepsy

The ENACT Trial: A Randomized, double-blind, placebo-controlled adjunctive treatment trial to evaluate the efficacy and safety of ENX-101 in patients with focal (partial onset) seizures

EU CTIS ID: 2022-501028-95-00

What this study is testing

To evaluate the efficacy of ENX-101 administered adjunctively with 1 to 4 antiseizure medications for the treatment of focal seizures [ Time Frame: Treatment Period (Day 1 to Day 56) compared to placebo ]

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Male or female aged 18 to 75 years, inclusive, at Screening
6. Has been treated with approved ASMs ≥ 2 years and is currently being treated with: at least one and no more than 4 ASMs at stable doses for at least 28 days before Screening (not including the rescue medication); dose adjustments should not be expected during the study
7. Use of benzodiazepines as rescue medication is allowed if such use is, on average, ≤ 1 time per week
8. Female patients a. Of non-childbearing potential, defined as either permanently sterilized (at least 4 months after surgical sterilization including bilateral salpingectomy, tubal ligation, or oophorectomy with or without hysterectomy) or post-menopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle-stimulating hormone level >40 IU/mL; in the event a patient's menopausal status has been clearly established and yet serum follicle-stimulating hormone levels are not consistent with a post-menopausal status, determination of the patient’s eligibility to be included in the study will be at the Investigator’s discretion following consultation with the Medical Monitor), and with a negative pregnancy test at Screening and Day 1 pre-dose; OR b. Of childbearing potential and willing to use 2 effective methods of contraception (i.e., established method of contraception + condom) or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the patient) from the start of the Baseline Period through 3 months after the last dose of study drug, and with a negative pregnancy test at Screening and Day 1 pre-dose
9. Male patients who, if fertile (defined as post-pubertal and not permanently sterile by orchidectomy or vasectomy) must be willing to use a condom or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the patient) from Day 1 through to 3 months after the last dose of study drug
4. Experiencing poorly controlled focal onset seizures [focal aware (simple partial) seizures with an observable component, focal impaired awareness (complex partial) seizures, or focal to bilateral tonic-clonic (secondarily generalised) seizures] despite adequate trials of proven effective medicines

You likely can't join if

1. EEG shows any pattern not consistent with focal etiology of seizures (e.g., generalized spike-wave)
25. Received an investigational drug within 90 days or 5 half lives, whichever is longer, prior to Screening, activation of an investigational device within 90 days prior to Screening, or currently in the follow up period of another interventional clinical trial at the time of Screening
3. Has genetic/idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut syndrome
10. Had Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS), or other neurostimulation for epilepsy device implanted or activated < 1 year prior to Screening, stimulation parameters have been stable for < 3 months, or battery life of unit not anticipated to extend for duration of trial
4. Has history of seizures that occur at such a high frequency they cannot be reliably counted (e.g., repetitive, cluster seizures) within the year prior to Screening
5. Has history of psychogenic non-epileptic seizures

See the full eligibility criteria

Who can join

1. Male or female aged 18 to 75 years, inclusive, at Screening
6. Has been treated with approved ASMs ≥ 2 years and is currently being treated with: at least one and no more than 4 ASMs at stable doses for at least 28 days before Screening (not including the rescue medication); dose adjustments should not be expected during the study
7. Use of benzodiazepines as rescue medication is allowed if such use is, on average, ≤ 1 time per week
8. Female patients a. Of non-childbearing potential, defined as either permanently sterilized (at least 4 months after surgical sterilization including bilateral salpingectomy, tubal ligation, or oophorectomy with or without hysterectomy) or post-menopausal (defined as amenorrhea for 12 consecutive months and documented plasma follicle-stimulating hormone level >40 IU/mL; in the event a patient's menopausal status has been clearly established and yet serum follicle-stimulating hormone levels are not consistent with a post-menopausal status, determination of the patient’s eligibility to be included in the study will be at the Investigator’s discretion following consultation with the Medical Monitor), and with a negative pregnancy test at Screening and Day 1 pre-dose; OR b. Of childbearing potential and willing to use 2 effective methods of contraception (i.e., established method of contraception + condom) or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the patient) from the start of the Baseline Period through 3 months after the last dose of study drug, and with a negative pregnancy test at Screening and Day 1 pre-dose
9. Male patients who, if fertile (defined as post-pubertal and not permanently sterile by orchidectomy or vasectomy) must be willing to use a condom or remain abstinent (where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the patient) from Day 1 through to 3 months after the last dose of study drug
4. Experiencing poorly controlled focal onset seizures [focal aware (simple partial) seizures with an observable component, focal impaired awareness (complex partial) seizures, or focal to bilateral tonic-clonic (secondarily generalised) seizures] despite adequate trials of proven effective medicines
10. Body mass index of 18 to 40 kg/m2 at Screening
11. Capable of giving written informed consent
12. Is willing to give written consent to have data entered into a study participant database
13. Patient is able to keep accurate seizure eDiary for duration of study
2. Diagnosed with focal (partial onset) epilepsy according to the International League Against Epilepsy (ILAE) 2017 classification of Epilepsy, as confirmed by the Epilepsy Study Consortium
3. Able to provide an imaging study(ies) [magnetic resonance imaging (MRI) scan strongly preferred yet computed tomography (CT) acceptable] obtained within the previous 10 years that can rule out a progressive cause of epilepsy
5. During the 3 months (84 days) immediately prior to Screening: • ≥ 3 observable focal onset seizures per 28-day period; • <10 seizures per day; • Any seizure-free interval no more than 21 days in length
6. During the 8-week Baseline Period prior to Day 1: • ≥ 6 observable focal onset seizures; • < 10 seizures per day; • No seizure-free interval of ≥ 21 days

What rules you out

1. EEG shows any pattern not consistent with focal etiology of seizures (e.g., generalized spike-wave)
25. Received an investigational drug within 90 days or 5 half lives, whichever is longer, prior to Screening, activation of an investigational device within 90 days prior to Screening, or currently in the follow up period of another interventional clinical trial at the time of Screening
3. Has genetic/idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut syndrome
10. Had Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS), or other neurostimulation for epilepsy device implanted or activated < 1 year prior to Screening, stimulation parameters have been stable for < 3 months, or battery life of unit not anticipated to extend for duration of trial
4. Has history of seizures that occur at such a high frequency they cannot be reliably counted (e.g., repetitive, cluster seizures) within the year prior to Screening
5. Has history of psychogenic non-epileptic seizures
6. Has history of status epilepticus within two years prior to Screening
7. Treatment of epilepsy with ASM was initiated < 2 years prior to Screening
8. Ingested excluded concomitant medication within 5 half lives or 28 days (whichever is longer) prior to Screening including: a. Chronic benzodiazepine (including clobazam) b. Felbamate initiated < 1 year prior to Screening c. Vigabatrin or ezogabine/retigabine d. Phenobarbital e. Primidone f. Oncologic medications g. Schizophrenia or psychosis medications h. Antiarrhythmic medications i. Medications used to treat malaria (except for chloroquine and hydroxychloroquine when used for Systemic lupus erythematosus [SLE] or rheumatoid arthritis) j. Medications for tuberculosis or HIV/AIDS k. Systemic corticosteroids (occasional use of topical corticosteroids is allowed) l. Medications that can increase intraocular pressure (Table 6 of the protocol) m. Medications known to prolong the QTc interval and with a known risk related to cause torsade de points (Table 7 of the protocol))
9. Had epilepsy surgery for tissue resection < 1 year prior to Screening or radiosurgery < 2 years prior to Screening
27. Unable to comply with the requirements of the study or, in the opinion of the Investigator, is unsuitable for the study
18. Has clinically significant, abnormal findings in serum chemistry, coagulation, hematology, or urinalysis results at Screening or Day 1 (pre-dose) including, but not limited to, elevated (> 3x upper limit of normal) alanine aminotransferase and/or aspartate aminotransferase and/or bilirubin at Screening or Day 1 (pre-dose); isolated gamma-glutamyl transferase elevation, chronic mild anemia or mild hyperglycaemia is acceptable
11. Initiated dietary therapy for epilepsy (e.g., ketogenic diet) < 3 months prior to Screening
12. Has significant progressive disorders or unstable medical conditions requiring acute intervention or that, in the Investigator’s opinion, may place the patient at risk or interfere with study outcome variables; including, but not limited to, cardiac, renal, neurologic (other than epilepsy), psychiatric, gastrointestinal, pulmonary, endocrinologic, hematologic, infectious, or immunologic disease or active malignancy requiring current or planned oncologic therapy Note: stable medical conditions (other than active malignancy) may be allowed as long as any pharmacologic therapy is at a stable dose and dosing regimen for at least 28 days prior to the start of Screening with no dosing changes planned or anticipated during the study, and doesn’t require any excluded medications per exclusion #8
13. Has any of the following cardiovascular health-related issues: a. any major cardiovascular events (e.g., myocardial infarct, unstable angina, acute coronary syndrome, coronary revascularization, stroke) within 3 months prior to screening. b. Congestive heart failure; New York Heart Association [NYHA] Class ≥ 2 c. Angina pectoris; Canadian Cardiovascular Society [CCS] Grade > 2 d. History of symptomatic ventricular tachycardia or torsade de pointes, personal or family history of sudden death or long QT syndrome or arrhythmias requiring antiarrhythmic therapy e. Mean QTcF Interval >450 msec at Screening or Baseline Day 1; if the QRS interval is >110msec, then the adjusted QTcF > 450 msec f. PR interval > 250 ms g. Second or third degree atrioventricular (AV) block
14. Based on ophthalmological examination performed during Screening, patient must not have, in the opinion of the ophthalmologist, any clinically significant lens opacity or ocular condition that may require medical or surgical intervention during the course of the trial
15. Has any psychiatric disorder where changes in pharmacotherapy are needed or anticipated during the study
16. Reports having experienced suicidal ideation (Type 4 or 5 on the C SSRS) within 6 months prior to Screening, any suicidal behavior within 2 years prior to Screening (any “Yes” answers on Suicidal Behavior section of C SSRS), more than 1 lifetime suicide attempt, and/or the Investigator assesses the patient to be a safety risk to him/herself or others
17. Has history or evidence of moderate or severe Substance Use Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th Edition)
26. Has known or suspected hypersensitivity to ENX-101 or any inactive ingredients used in its formulation or in placebo
19. Has evidence of renal impairment defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2
2. Has history of focal onset seizures which involve subjective sensory or psychic phenomena without impairment of consciousness or awareness (formerly referred to as simple partial seizures without observable component) as their only seizure type
20. Has evidence of hepatic impairment defined as bilirubin levels >1.5 times the upper limit of the normal and/or AST, ALT and/or alkaline phosphatase > 2 times the upper limit of the normal
21. Has clinically significant, abnormal findings in vital sign assessments, at Screening or Day 1 (pre-dose)
22. Has history of hepatitis B or hepatitis C or demonstration of hepatitis B surface antigen or hepatitis C antibody at Screening
23. Has history of HIV infection or demonstration of HIV antibodies at Screening
24. Has a positive test for COVID-19 at Screening or Day 1 (pre-dose)

The study team makes the final eligibility decision.

Where it's taking place

United States
United Kingdom
Australia

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; United Kingdom; Australia. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.