AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
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ClinicalTrials.gov Identifier: NCT06063850 |
Recruitment Status :
Recruiting
First Posted : October 3, 2023
Last Update Posted : November 14, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Mesial Temporal Lobe Epilepsy | Genetic: AAV9-hSyn1-miGRIK2 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 12 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | Single (Outcomes Assessor) |
Masking Description: | EEG readers will be blinded |
Primary Purpose: | Treatment |
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) |
Estimated Study Start Date : | November 17, 2023 |
Estimated Primary Completion Date : | November 30, 2026 |
Estimated Study Completion Date : | June 30, 2027 |
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 Name: AMT-260 |
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 Name: AMT-260 |
- Adverse Events [ Time Frame: 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.
- Seizure Frequency [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 1 year ]qPCR analyses will be used to measure AAV9 vector shedding in Cerebrospinal fluid, Blood Serum, Urine, Saliva.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 pathology- related 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06063850
Contact: Carlien ter Mors | (339) 970-7000 | amt_260_clinical_trials@uniqure.com | |
Contact: Stephanie Verweij | (339) 970-7000 | amt_260_clinical_trials@uniqure.com |
United States, New Jersey | |
Northeast Regional Epilepsy Group | Recruiting |
Hackensack, New Jersey, United States, 07601 | |
Contact: Hardik Rana 551-497-5000 | |
United States, Ohio | |
Ohio State University | Not yet recruiting |
Columbus, Ohio, United States, 43210 | |
Contact: Elizabeth A Wiley 614-293-3660 Elizabeth.Wiley@osumc.edu | |
Principal Investigator: Dr Singh |
Study Director: | Andreas Borta | uniQure France SAS |
Responsible Party: | uniQure France SAS |
ClinicalTrials.gov Identifier: | NCT06063850 |
Other Study ID Numbers: |
CT-AMT-260-01 |
First Posted: | October 3, 2023 Key Record Dates |
Last Update Posted: | November 14, 2023 |
Last Verified: | November 2023 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Epilepsy Temporal Lobe Hippocampal Sclerosis Epileptic Syndromes |
Epilepsy Epilepsy, Temporal Lobe Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Epilepsies, Partial Epileptic Syndromes |