search
Back to results

AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy

Primary Purpose

Mesial Temporal Lobe Epilepsy

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV9-hSyn1-miGRIK2
Sponsored by
uniQure France SAS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mesial Temporal Lobe Epilepsy focused on measuring Epilepsy, Temporal Lobe, Hippocampal Sclerosis, Epileptic Syndromes

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: AMT-260 starting dose

Cohort 2: AMT-260 adapted dose

Arm Description

N# of treated - 6

N# of treated - 6 Dose is dependent on the DSMB recommendation.

Outcomes

Primary Outcome Measures

Adverse Events
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
Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.
Quality of Life in Epilepsy Inventory-31 (QOLIE 31)
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)
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)
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)
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).
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).
qPCR analyses will be used to measure AAV9 vector shedding in Cerebrospinal fluid, Blood Serum, Urine, Saliva.

Full Information

First Posted
September 1, 2023
Last Updated
September 25, 2023
Sponsor
uniQure France SAS
search

1. Study Identification

Unique Protocol Identification Number
NCT06063850
Brief Title
AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
uniQure France SAS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mesial Temporal Lobe Epilepsy
Keywords
Epilepsy, Temporal Lobe, Hippocampal Sclerosis, Epileptic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
Outcomes Assessor
Masking Description
EEG readers will be blinded
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: AMT-260 starting dose
Arm Type
Experimental
Arm Description
N# of treated - 6
Arm Title
Cohort 2: AMT-260 adapted dose
Arm Type
Experimental
Arm Description
N# of treated - 6 Dose is dependent on the DSMB recommendation.
Intervention Type
Genetic
Intervention Name(s)
AAV9-hSyn1-miGRIK2
Other Intervention Name(s)
AMT-260
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adverse Events
Description
Occurrence of Adverse Events during the period of 1 year after AMT-260 administration, including seriousness, severity, and causal relationship to AMT-260.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Seizure Frequency
Description
Change in seizure frequency, comparing baseline to the 1 year period after AMT-260 administration.
Time Frame
1 year
Title
Quality of Life in Epilepsy Inventory-31 (QOLIE 31)
Description
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.
Time Frame
1 year
Title
Patient Health Questionnaire (PHQ9)
Description
Change from baseline in responses to the PHQ9 will be used to assess the level of depression in participants throughout the study.
Time Frame
1 year
Title
State Trait Anxiety Inventory (STAI)
Description
Change from baseline in responses to the STAI questionnaire will be used to assess trait anxiety and state anxiety in participants throughout the study.
Time Frame
1 year
Title
Pittsburgh Sleep Quality Index (PSQI)
Description
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.
Time Frame
1 year
Title
miRNA in human biofluid (copies/qPCR reaction).
Description
Stem-loop RT-qPCR analyses will be used to measure miRNA in Cerebrospinal fluid, Blood Serum, Urine, Saliva.
Time Frame
1 year
Title
AAV9 vector in human biofluid (copies/qPCR reaction).
Description
qPCR analyses will be used to measure AAV9 vector shedding in Cerebrospinal fluid, Blood Serum, Urine, Saliva.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carlien ter Mors
Phone
(339) 970-7000
Email
amt_260_clinical_trials@uniqure.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie Verweij
Phone
(339) 970-7000
Email
amt_260_clinical_trials@uniqure.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Borta
Organizational Affiliation
uniQure France SAS
Official's Role
Study Director
Facility Information:
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth A Wiley
Phone
614-293-3660
Email
Elizabeth.Wiley@osumc.edu
First Name & Middle Initial & Last Name & Degree
Dr Singh

12. IPD Sharing Statement

Learn more about this trial

AMT-260 Gene Therapy Study in Adults With Unilateral Refractory Mesial Temporal Lobe Epilepsy

We'll reach out to this number within 24 hrs