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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
Sponsor:
Information provided by (Responsible Party):
UniQure Biopharma B.V. ( uniQure France SAS )

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
Mesial Temporal Lobe Epilepsy Genetic: AAV9-hSyn1-miGRIK2 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.

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Seizure Frequency [ Time Frame: 1 year ]
    Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult, 18-65 years of age, inclusive, capable of giving informed consent.
  2. Diagnosis of unilateral refractory MTLE for ≥360 days, confirmed by an Epilepsy Monitoring Unit.
  3. 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).
  4. 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.
  5. Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
  6. Montreal Cognitive Assessment (MoCA) total score ≥26.
  7. No evidence of focal neurocognitive dysfunction, inconsistent with disease pathology- related MRI and (18F)FDG-PET findings.
  8. 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.
  9. For WOCBP only: Negative pregnancy test.

Exclusion Criteria:

  1. 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).
  2. Any other contraindications for generalized anesthesia or surgery.
  3. 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.
  4. Any psychogenic nonepileptic seizures within the last year.
  5. Any seizures with contralateral or extra-temporal ictal onset on EEG.
  6. 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.
  7. Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.

Information from the National Library of Medicine

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


Contacts
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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

Locations
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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         
Sponsors and Collaborators
uniQure France SAS
Investigators
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Study Director: Andreas Borta uniQure France SAS
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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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UniQure Biopharma B.V. ( uniQure France SAS ):
Epilepsy
Temporal Lobe
Hippocampal Sclerosis
Epileptic Syndromes
Additional relevant MeSH terms:
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Epilepsy
Epilepsy, Temporal Lobe
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epilepsies, Partial
Epileptic Syndromes