- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06063850
AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
November 13, 2023 updated by: uniQure France SAS
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 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).
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Estimated)
12
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Carlien ter Mors
- Phone Number: (339) 970-7000
- Email: amt_260_clinical_trials@uniqure.com
Study Contact Backup
- Name: Stephanie Verweij
- Phone Number: (339) 970-7000
- Email: amt_260_clinical_trials@uniqure.com
Study Locations
-
-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- Recruiting
- Northeast Regional Epilepsy Group
-
Contact:
- Hardik Rana
- Phone Number: 551-497-5000
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Not yet recruiting
- Ohio State University
-
Contact:
- Elizabeth A Wiley
- Phone Number: 614-293-3660
- Email: Elizabeth.Wiley@osumc.edu
-
Principal Investigator:
- Dr Singh
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: AMT-260 starting dose
N# of treated - 6
|
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. |
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Seizure Frequency
Time Frame: 1 year
|
Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Andreas Borta, uniQure France SAS
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
November 17, 2023
Primary Completion (Estimated)
November 30, 2026
Study Completion (Estimated)
June 30, 2027
Study Registration Dates
First Submitted
September 1, 2023
First Submitted That Met QC Criteria
September 25, 2023
First Posted (Actual)
October 3, 2023
Study Record Updates
Last Update Posted (Estimated)
November 14, 2023
Last Update Submitted That Met QC Criteria
November 13, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CT-AMT-260-01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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