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

NCT06063850 · UniQure Biopharma B.V.
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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)
About this study
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.
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).
Study design
Enrollment target: 12 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-06-12
Estimated completion: 2031-12
Last updated: 2026-04-06
Interventions
Genetic: AAV9-hSyn1-miGRIK2
Primary outcomes
  • To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE. (1 year)
Sponsor
UniQure Biopharma B.V. · industry
Contacts & investigators
ContactuniQure · contact · medinfo@uniqure.com · 1-866-520-1257
InvestigatorClinical Development Lead · study_director, uniQure France SAS
All locations (18)
University of Alabama at BirminghamRecruiting
Birmingham, Alabama, United States
Mayo Clinic ArizonaRecruiting
Phoenix, Arizona, United States
Stanford UniversityRecruiting
Palo Alto, California, United States
Mayo Clinic FloridaRecruiting
Jacksonville, Florida, United States
Kansas University Medical CenterRecruiting
Kansas City, Kansas, United States
Johns Hopkins School of MedicineRecruiting
Baltimore, Maryland, United States
Midatlantic Epilepsy and Sleep CenterRecruiting
Bethesda, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Corewell HealthRecruiting
Grand Rapids, Michigan, United States
Dartmouth Hitchcock Medical CenterRecruiting
Lebanon, New Hampshire, United States
Northeast Regional Epilepsy GroupRecruiting
Hackensack, New Jersey, United States
Robert Wood Johnson HospitalRecruiting
New Brunswick, New Jersey, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Ohio State UniversityRecruiting
Columbus, Ohio, United States
Hospital of the University of PennsylvaniaRecruiting
Philadelphia, Pennsylvania, United States
Allegheny Health NetworkRecruiting
Pittsburgh, Pennsylvania, United States
Baylor Scott & White Medical CenterRecruiting
Austin, Texas, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy · TrialPath