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NCT06063850PHASE1, PHASE2Recruiting

AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy

UniQure Biopharma B.V.

Start Date

6/12/2024

Completion Date

12/1/2031

Summary

The main goals of this clinical study are to learn if AMT-260 is safe and tolerable and works to reduce the frequency of seizures in adults with unilateral mesial temporal lobe epilepsy (MTLE).

Detailed Description

In this first clinical study of AMT-260, two dose levels will be studied to find the best dose of AMT-260. All eligible participants will receive AMT-260 at one of the two dose levels (i.e., there is no placebo in this study). AMT-260 is intended for a one-time administration, without the need to remove or destroy any part of the brain. Participation in this study would not prevent later pursuit of other treatment options. Participants will be monitored through study site visits, telephone calls, blood tests, and questionnaires about how their seizures affect daily life. Participants will record seizures using an electronic seizure diary.

Eligibility Criteria

Age Range: 18 years to 75 years

Inclusion Criteria: * Diagnosis of unilateral refractory MTLE * History of seizures with an average of ≥ 2 documented focal impaired awareness seizures or focal to bilateral tonic-clonic seizures per 30-day period over the 3 month Retrospective Period. * On a stable type and dose regimen of up to a maximum of 4 approved Anti Seizure Drugs for at least 1 month prior to the Retrospective Period. * Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus * No evidence of focal neurocognitive dysfunction, inconsistent with disease pathology- related MRI and/or (18F)FDG-PET findings. * Women of childbearing potential (WOCBP) and fertile male subjects must be willing and able to use highly effective methods of birth control consistently and correctly throughout the study. * For WOCBP only: Negative pregnancy test. Exclusion Criteria: * Implanted devices that would contraindicate MRI; MRI-compatible devices must be implanted ≥3 months prior to Screening (vagus nerve stimulation devices will be up to discretion of the Investigator). * Any other contraindications to general anesthesia, surgery, or intra-operative magnetic resonance imaging (MRI). * Medications that could confound clinical (e.g., antipsychotic medication and anti-viral therapy) and laboratory evaluations or could affect a participant's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule. * Bilateral or multifocal epilepsy; or inability to confidently lateralize seizure onset. * Dementia or other progressive neurological disorders and progressive brain lesions. * Previous major disease-unrelated neurosurgical intervention due to intracranial tumor, trauma, or bleeding and/or history of previous intracranial surgery for treatment of epileptic seizures, not including diagnostic stereo-EEG. * MRI evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology. * Status epilepticus within the year prior to Screening.

Interventions

GENETIC

AAV9-hSyn1-miGRIK2

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Conditions

Mesial Temporal Lobe Epilepsy

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35294-0021

United States

Mayo Clinic Arizona

Phoenix, Arizona 85054

United States

Stanford University

Palo Alto, California 94304

United States

Mayo Clinic Florida

Jacksonville, Florida 32224

United States

Kansas University Medical Center

Kansas City, Kansas 66160

United States

Johns Hopkins School of Medicine

Baltimore, Maryland 21287

United States

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland 20817

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Corewell Health

Grand Rapids, Michigan 49503

United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire 03756

United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey 07601

United States

Robert Wood Johnson Hospital

New Brunswick, New Jersey 08901

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Ohio State University

Columbus, Ohio 43210

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Allegheny Health Network

Pittsburgh, Pennsylvania 15212

United States

Baylor Scott & White Medical Center

Austin, Texas 78735

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States