ENACT: A Study of ENX-101 as Adjunctive Treatment in Patients With Focal Seizures

Study Overview
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Brief Summary
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The ENACT trial is designed to evaluate the efficacy and safety of ENX-101 administered adjunctively to current therapy in reducing seizure frequency in patients diagnosed with focal (partial onset) epilepsy and treated with 1 to 4 antiseizure medications yet still experiencing seizures.

Official Title
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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

Conditions
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Focal Epilepsy

Intervention / Treatment
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* Drug: ENX-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 75 years, inclusive, at Screening 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 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 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, 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, Has been treated with antiseizure medications (ASMs) ≥ 2 years and currently being treated with: One to 4 ASMs at stable doses for at least 28 days before Screening (not including the rescue medication) Dose adjustments not expected during study Exclusion Criteria: EEG shows any pattern not consistent with focal etiology of seizures (e.g., generalized spike-wave) 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 Has genetic/idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut syndrome 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 Has history of psychogenic non-epileptic seizures Has history of status epilepticus within two years prior to Screening Treatment of epilepsy with ASM was initiated < 2 years prior to Screening Ingested excluded concomitant medication within 5 half lives or 28 days (whichever is longer) prior to Screening Had epilepsy surgery for tissue resection < 1 year prior to Screening or radiosurgery < 2 years prior to Screening 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 Initiated dietary therapy for epilepsy (e.g., ketogenic diet) < 3 months prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENX-101 15mg daily<br> | Drug: ENX-101<br>* Adjunctive treatment to current antiseizure medication<br>|
| Experimental: ENX-101 30mg daily<br> | Drug: ENX-101<br>* Adjunctive treatment to current antiseizure medication<br>|
| Placebo Comparator: Placebo daily<br> | Drug: ENX-101<br>* Adjunctive treatment to current antiseizure medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of ENX-101 administered adjunctively with 1 to 4 antiseizure medications for the treatment of focal seizures | The median percent change from baseline in 28-day focal seizure frequency (focal aware motor with observable component, focal impaired awareness, or focal to bilateral tonic-clonic seizures) compared to placebo | Day 1 to end of the Treatment Period (Day 56) compared to placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of ENX-101 administered adjunctively with 1 to 4 antiseizure medications for the treatment of focal seizures | The responder rate defined as the percent of patients who experience a 50% or greater reduction from baseline in seizure frequency in the Treatment Period compared to placebo (designated as primary for the European Medicines Agency) | Treatment Period (Day 1 to Day 56) compared to placebo | 
| To evaluate the efficacy of ENX-101 | The percent of patients who are seizure free during the last 28 days of the Treatment Period | Treatment Period (Day 29 to Day 56) compared to placebo | 
| To evaluate the efficacy of ENX-101 | The percent of patients who are seizure free during the entire Treatment Period | Treatment Period (Day 1 to Day 56) compared to placebo |