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

August 20, 2026 updated by: UniQure Biopharma B.V.

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-0021
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
        • Principal Investigator:
          • Jerzy P Szaflarski, MD, PhD
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Arizona
        • Contact:
        • Principal Investigator:
          • Jonathon Parker, MD
    • California
      • Palo Alto, California, United States, 94304
        • Completed
        • Stanford University
    • Florida
      • Jacksonville, Florida, United States, 32224
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • Kansas University Medical Center
        • Contact:
        • Principal Investigator:
          • P Landazuri, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins School of Medicine
        • Contact:
        • Principal Investigator:
          • Joon Kang, MD
      • Bethesda, Maryland, United States, 20817
        • Completed
        • Midatlantic Epilepsy and Sleep Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Mark Richardson, MD, PhD
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Corewell Health
        • Contact:
        • Principal Investigator:
          • David Burdette, MD
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Recruiting
        • Dartmouth Hitchcock Medical Center
        • Principal Investigator:
          • Barbara Jobst, MD
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Northeast Regional Epilepsy Group
        • Contact:
        • Principal Investigator:
          • Asfi Rafiuddin
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Robert Wood Johnson Hospital
        • Principal Investigator:
          • Robert E Gross, MD, PhD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Imad Najm, MD
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University
        • Contact:
        • Principal Investigator:
          • James Elder, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny Health Network
        • Contact:
        • Principal Investigator:
          • Alexander Whiting, MD
    • Texas
      • Austin, Texas, United States, 78735
        • Recruiting
        • Baylor Scott & White Medical Center
        • Contact:
        • Principal Investigator:
          • Victor H Gonzalez Montoya, MD, FAES
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Contact:
        • Principal Investigator:
          • Kunal Gupta, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AMT-260
Cohort 1: AMT-260 starting dose (1.0x 10E12 gc/mL). Cohort 2: AMT-260 adapted dose (6.0x 10E11 gc/mL or 3.0x 10E12 gc/mL).
Genetic: AAV9-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.
Other Names:
  • AMT-260

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE.
Time Frame: 1 year
Occurrence of Adverse Events during the period of 1 year after AMT-260 administration, including seriousness, severity, and causal relationship to AMT-260.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate first signs of efficacy of AMT-260.
Time Frame: 1 year
Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.
1 year
To evaluate the biodistribution properties of AMT-260.
Time Frame: 1 year
Blood, urine, saliva, and CSF samples will be collected and evaluated for vector DNA shedding at each timepoint.
1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the long-term safety and efficacy of AMT-260 in adults with unilateral refractory MTLE.
Time Frame: up to 5 years
Occurrence of Adverse Events during the period of 1 to 5 years after AMT-260 administration, including seriousness.
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UniQure Biopharma B.V.

Investigators

  • Study Director: Clinical Development Lead, uniQure France SAS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2024

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

December 1, 2031

Study Registration Dates

First Submitted

September 1, 2023

First Submitted That Met QC Criteria

September 25, 2023

First Posted (Actual)

October 3, 2023

Study Record Updates

Last Update Posted (Actual)

August 24, 2026

Last Update Submitted That Met QC Criteria

August 20, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-AMT-260-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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