AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: AMT-260 starting dose N# of treated - 6 |
Genetic: AAV9-hSyn1-miGRIK2
AMT-260 is an AAV9 gene therapy product that locally delivers miRNA silencing technology to target the GRIK2 gene and suppress aberrantly expressed GluK2 containing kainate receptors. Intervention will be a one-time intracerebral administration of AMT-260.
Other Names:
|
| Experimental: Cohort 2: AMT-260 adapted dose N# of treated - 6 Dose is dependent on the DSMB recommendation. |
Genetic: AAV9-hSyn1-miGRIK2
AMT-260 is an AAV9 gene therapy product that locally delivers miRNA silencing technology to target the GRIK2 gene and suppress aberrantly expressed GluK2 containing kainate receptors. Intervention will be a one-time intracerebral administration of AMT-260.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Adverse Events [1 year]
Occurrence of Adverse Events during the period of 1 year after AMT-260 administration, including seriousness, severity, and causal relationship to AMT-260.
Secondary Outcome Measures
- Seizure Frequency [1 year]
Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.
- Quality of Life in Epilepsy Inventory-31 (QOLIE 31) [1 year]
Change from baseline in responses to the QOLIE-31 questionnaire will be assessed on the following subscales; seizure worry, overall quality of life, emotional well-being, energy-fatigue, cognitive function, medication effects, and social functioning.
- Patient Health Questionnaire (PHQ9) [1 year]
Change from baseline in responses to the PHQ9 will be used to assess the level of depression in participants throughout the study.
- State Trait Anxiety Inventory (STAI) [1 year]
Change from baseline in responses to the STAI questionnaire will be used to assess trait anxiety and state anxiety in participants throughout the study.
- Pittsburgh Sleep Quality Index (PSQI) [1 year]
Change from baseline in responses to the PSQI questionnaire will be assessed on the following components; subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction.
- miRNA in human biofluid (copies/qPCR reaction). [1 year]
Stem-loop RT-qPCR analyses will be used to measure miRNA in Cerebrospinal fluid, Blood Serum, Urine, Saliva.
- AAV9 vector in human biofluid (copies/qPCR reaction). [1 year]
qPCR analyses will be used to measure AAV9 vector shedding in Cerebrospinal fluid, Blood Serum, Urine, Saliva.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adult, 18-65 years of age, inclusive, capable of giving informed consent.
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Diagnosis of unilateral refractory MTLE for ≥360 days, confirmed by an Epilepsy Monitoring Unit.
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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).
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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.
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Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
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Montreal Cognitive Assessment (MoCA) total score ≥26.
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No evidence of focal neurocognitive dysfunction, inconsistent with disease pathology- related MRI and (18F)FDG-PET findings.
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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.
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For WOCBP only: Negative pregnancy test.
Exclusion Criteria:
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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).
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Any other contraindications for generalized anesthesia or surgery.
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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.
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Any psychogenic nonepileptic seizures within the last year.
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Any seizures with contralateral or extra-temporal ictal onset on EEG.
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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.
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Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- uniQure France SAS
Investigators
- Study Director: Andreas Borta, uniQure France SAS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT-AMT-260-01