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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 )

Tracking Information
First Submitted Date  ICMJE September 1, 2023
First Posted Date  ICMJE October 3, 2023
Last Update Posted Date November 14, 2023
Estimated Study Start Date  ICMJE November 17, 2023
Estimated Primary Completion Date November 30, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2023)		 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2023)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
Official Title  ICMJE 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)
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
EEG readers will be blinded
Primary Purpose: Treatment
Condition  ICMJE Mesial Temporal Lobe Epilepsy
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Cohort 1: AMT-260 starting dose
    N# of treated - 6
    Intervention: Genetic: AAV9-hSyn1-miGRIK2
  • Experimental: Cohort 2: AMT-260 adapted dose

    N# of treated - 6

    Dose is dependent on the DSMB recommendation.

    Intervention: Genetic: AAV9-hSyn1-miGRIK2
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 25, 2023)		 12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2027
Estimated Primary Completion Date November 30, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06063850
Other Study ID Numbers  ICMJE CT-AMT-260-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party UniQure Biopharma B.V. ( uniQure France SAS )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE uniQure France SAS
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Andreas Borta uniQure France SAS
PRS Account UniQure Biopharma B.V.
Verification Date November 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP