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Recruiting NCT06063850

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

Phase I / Phase II Interventional Mesial Temporal Lobe Epilepsy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: AAV9-hSyn1-miGRIK2.
Who it may be relevant to
Registry conditions: Mesial Temporal Lobe Epilepsy. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

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)

Overview

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.

Interventions

  • 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.

Primary outcome measures

  • To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE. [Time frame: 1 year]
Secondary outcome measures (2)
  • To evaluate first signs of efficacy of AMT-260. [Time frame: 1 year]
  • To evaluate the biodistribution properties of AMT-260. [Time frame: 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 18 centers
  • University of Alabama at Birmingham — Birmingham
  • Mayo Clinic Arizona — Phoenix
  • Stanford University — Palo Alto
  • Mayo Clinic Florida — Jacksonville
  • Kansas University Medical Center — Kansas City
  • Johns Hopkins School of Medicine — Baltimore
  • Midatlantic Epilepsy and Sleep Center — Bethesda
  • Massachusetts General Hospital — Boston
  • … and 10 more centers

Identifiers

NCT: NCT06063850 · CT-AMT-260-01

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗