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

Overview

This is a study of AMT-260 in Adults with Unilateral Refractory Mesial Temporal Lobe Epilepsy (MTLE). It is designed to investigate the Safety, Tolerability, and Efficacy of AMT-260 in Adults with MTLE Administered via Magnetic Resonance Imaging (MRI)-guided Convection-enhanced Delivery (CED).

Description

The first-in-human Phase I/IIa U.S. trial consists of two parts. The first part is a multi-center, open-label trial with two dosing cohorts of six patients each to assess safety, tolerability, and first signs of efficacy of AMT-260 in patients with refractory unilateral MTLE. The second part is expected be a randomized, controlled trial to generate proof of concept (POC) data.

Eligibility

Inclusion Criteria:

1. Adult, 18-65 years of age, inclusive, capable of giving informed consent.
2. Diagnosis of unilateral refractory MTLE for ≥360 days, confirmed by an Epilepsy Monitoring Unit.
3. History of seizures with on average ≥ 2 focal onset impaired awareness seizures per 30-day period during the Retrospective Period (3 months prior to screening).
4. Currently on a stable type and dose regimen of up to a maximum of 4 approved ASDs, for ≥3 months prior to the Retrospective Period.
5. Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
6. Montreal Cognitive Assessment (MoCA) total score ≥26.
7. No evidence of focal neurocognitive dysfunction, inconsistent with disease pathologyrelated MRI and (18F)FDG-PET findings.
8. 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 and for ≥360 days following AMT-260 administration.
9. For WOCBP only: Negative pregnancy test.

Exclusion Criteria:

1. 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).
2. Any other contraindications for generalized anesthesia or surgery.
3. Medications that could confound clinical (e.g., antipsychotic medication and anti-viral therapy) and laboratory evaluations or could affect a subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
4. Any psychogenic nonepileptic seizures within the last year.
5. Any seizures with contralateral or extra-temporal ictal onset on EEG.
6. 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.
7. Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.