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:
- Adult, 18-65 years of age, inclusive, capable of giving informed consent.
- Diagnosis of unilateral refractory MTLE for ≥360 days, confirmed by an Epilepsy Monitoring Unit.
- 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).
- 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.
- Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
- Montreal Cognitive Assessment (MoCA) total score ≥26.
- No evidence of focal neurocognitive dysfunction, inconsistent with disease pathologyrelated MRI and (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 and for ≥360 days following AMT-260 administration.
- 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 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 subject's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
- Any psychogenic nonepileptic seizures within the last year.
- Any seizures with contralateral or extra-temporal ictal onset on EEG.
- 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.
- Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.