Gene therapy for adults with 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)

This study is testing a new gene therapy called AMT-260 to see if it can help adults with a type of epilepsy called mesial temporal lobe epilepsy by reducing their seizures.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: UniQure Biopharma B.V. (industry)
• Locations: 18 sites (Birmingham, Alabama and 17 other locations)
• Trial ID: NCT06063850 on ClinicalTrials.gov

What this trial studies

This clinical study aims to evaluate the safety, tolerability, and efficacy of AMT-260, a gene therapy, in reducing seizure frequency in adults diagnosed with unilateral mesial temporal lobe epilepsy (MTLE). Participants will receive one of two dose levels of AMT-260, with no placebo involved, and will be closely monitored through site visits, phone calls, blood tests, and questionnaires. The study will also involve participants recording their seizures using an electronic diary to assess the impact on their daily lives.

Who should consider this trial

Good fit: Ideal candidates are adults with a diagnosis of unilateral refractory mesial temporal lobe epilepsy who have a history of frequent seizures despite treatment.

Not a fit: Patients with implanted devices contraindicating MRI or those without a confirmed unilateral seizure focus may not benefit from this study.

Why it matters

Potential benefit: If successful, this gene therapy could significantly reduce seizure frequency and improve the quality of life for patients with refractory MTLE.

How similar studies have performed: While gene therapy approaches for epilepsy are emerging, this specific application of AMT-260 is novel and has not been extensively tested in prior studies.

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 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 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 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).

Where this trial is running

Birmingham, Alabama and 17 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (RECRUITING)
• Mayo Clinic Arizona — Phoenix, Arizona, United States (RECRUITING)
• Stanford University — Palo Alto, California, United States (RECRUITING)
• Mayo Clinic Florida — Jacksonville, Florida, United States (RECRUITING)
• Kansas University Medical Center — Kansas City, Kansas, United States (RECRUITING)
• Johns Hopkins School of Medicine — Baltimore, Maryland, United States (RECRUITING)
• Midatlantic Epilepsy and Sleep Center — Bethesda, Maryland, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)
• Corewell Health — Grand Rapids, Michigan, United States (RECRUITING)
• Dartmouth Hitchcock Medical Center — Lebanon, New Hampshire, United States (RECRUITING)
• Northeast Regional Epilepsy Group — Hackensack, New Jersey, United States (RECRUITING)
• Robert Wood Johnson Hospital — New Brunswick, New Jersey, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)
• Ohio State University — Columbus, Ohio, United States (RECRUITING)
• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)
• Allegheny Health Network — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Baylor Scott & White Medical Center — Austin, Texas, United States (RECRUITING)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (RECRUITING)

Study contacts

• Study coordinator: uniQure

Conditions: Mesial Temporal Lobe Epilepsy, Epilepsy, Temporal Lobe, Hippocampal Sclerosis, Epileptic Syndromes