Clinical trial NCT06063850: AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Mesial Temporal Lobe Epilepsy
Keywords: Epilepsy
Temporal Lobe
Hippocampal Sclerosis
Epileptic Syndromes
Lead sponsor: UniQure Biopharma B.V.
Sponsor class: INDUSTRY
First posted: 2023-10-03
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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 ictal 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.

Primary outcomes:
measure: To evaluate the safety and tolerability of AMT-260 in adults with unilateral refractory MTLE.
timeFrame: 1 year
Secondary outcomes:
measure: To evaluate first signs of efficacy of AMT-260.
timeFrame: 1 year
measure: To evaluate the biodistribution properties of AMT-260.
timeFrame: 1 year
Other outcomes:
measure: To evaluate the long-term safety and efficacy of AMT-260 in adults with unilateral refractory MTLE.
timeFrame: up to 5 years
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Bethesda
country: United States
facility: Midatlantic Epilepsy and Sleep Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson Hospital
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Austin
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: uniQure France SAS
name: Clinical Development Lead
role: STUDY_DIRECTOR
References: