RecruitingPhase 1Phase 2NCT06063850

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

A Multi-center, Phase 1/2a, First-in-human (FIH) Study Investigating the Safety, Tolerability, and Efficacy of AMT-260 in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy (MTLE) Administered Via Magnetic Resonance Imaging (MRI)-Guided Convection-enhanced Delivery (CED)


Sponsor

UniQure Biopharma B.V.

Enrollment

12 participants

Start Date

Jun 12, 2024

Study Type

INTERVENTIONAL

Conditions

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).


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria7

  • 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 in the 3 months prior to screening.
  • On a stable type and dose regimen of up to a maximum of 4 approved Anti Seizure Drugs for at least 6 months prior to screening.
  • 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 Criteria8

  • 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 for generalized anesthesia or surgery.
  • 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.
  • Any seizures with contralateral or extra-temporal icta onset captured on EEG.
  • 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.
  • Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.
  • Inadequate vaccination status (including flu shots and other relevant immunizations such as COVID-19 per local guidelines and regulations).

Interventions

GENETICAAV9-hSyn1-miGRIK2

AMT-260 is an AAV9 gene therapy product that locally delivers miRNA silencing technology to target the GRIK2 gene and suppress aberrantly expressed GluK2 containing kainate receptors. Intervention will be a one-time intracerebral administration of AMT-260.


Locations(18)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Stanford University

Palo Alto, California, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Kansas University Medical Center

Kansas City, Kansas, United States

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Midatlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Corewell Health

Grand Rapids, Michigan, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Northeast Regional Epilepsy Group

Hackensack, New Jersey, United States

Robert Wood Johnson Hospital

New Brunswick, New Jersey, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Allegheny Health Network

Pittsburgh, Pennsylvania, United States

Baylor Scott & White Medical Center

Austin, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

View Full Details on ClinicalTrials.gov

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NCT06063850