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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: ENX-101

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Downey, California, United States, 90242
      • Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida Research Institute of Orlando
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33155
      • D&H National Research Centers
    • Miami, Florida, United States, 33032
      • Royal Care Medical Research Corporation
    • Miami, Florida, United States, 33155
      • S&G Research Center Corp.
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Orlando, Florida, United States, 32825
      • Comprehensive Neurology Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Illinois
    • Peoria, Illinois, United States, 61603
      • OSF HealthCare Illinois Neurological Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Health System
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Partners Neurology
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Oakland University William Beaumont School of Medicine
    • Plymouth, Michigan, United States, 48170
      • SRI International
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Advanced Clinical Research Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Somnos Clinical Research/Neurology Associates
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Regional Epilepsy Group
    • Livingston, New Jersey, United States, 07039
      • Institute of Neurology and Neurosurgery at Saint Barnabas LLC
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
    • Rochester, New York, United States, 14618
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 28204
      • Atrium Health
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuroscience Research Center, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 42101
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • DJL Clinical Research
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Mt. Olympus Medical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 to 75 years, inclusive, at Screening
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

4. 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,

5. 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,

6. 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:

1. EEG shows any pattern not consistent with focal etiology of seizures (e.g., generalized spike-wave)
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
3. Has genetic/idiopathic generalized epilepsies or combined generalized and focal epilepsies, including a history of Lennox-Gastaut syndrome
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
9. Had epilepsy surgery for tissue resection < 1 year prior to Screening or radiosurgery < 2 years prior to Screening
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
11. Initiated dietary therapy for epilepsy (e.g., ketogenic diet) < 3 months prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Engrail Therapeutics INC

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2022
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Epilepsies, Partial
• Other Study ID Numbers: ENX-101-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No