search
Back to results

Lentiviral Gene Therapy for Epilepsy

Primary Purpose

Drug Resistant Epilepsy

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
lentiviral gene therapy
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug Resistant Epilepsy focused on measuring lentiviral gene therapy, brain, surgery, drug resistant epilepsy

Eligibility Criteria

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

Inclusion Criteria:

SCREENING/PRE-CONSENT:

  1. Female and male patients with refractory focal epilepsy
  2. Aged ≥ 18 years (no upper age limit but deemed medically fit for surgery with a life expectancy of at least 5 years)
  3. Patient lives within 1 hour of transfer to an acute neurosurgical unit
  4. Being considered for resective brain surgery (to remove the epileptogenic focus) based on first-stage preoperative assessments carried out as part of routine clinical care within 2 years of registration, showing:

    4.1. Absence of vascular brain lesions or vascular malformations and/or cancer in the resection area (as confirmed on MRI) 4.2. Absence of active, untreated psychiatric disease in the opinion of the treating clinician (as confirmed by neuropsychiatric assessment) 4.3. Patient requires second-stage intracranial EEG investigations to be carried out via burr hole surgery to further assess eligibility for resective brain surgery

    PRE-REGISTRATION:

  5. Patient deemed clinically suitable for resective brain surgery (i.e. a single region of seizure onset in the neocortex has been identified, and it does not overlap with areas necessary for critical functions such as language), as confirmed by intracranial EEG investigations
  6. Patients who are women of childbearing potential (WOCBP), or male patients with female partners who are WOCBP or pregnant must agree to use highly effective methods of contraception from the time consent is signed until three months after treatment. Men (if applicable), must also advise their female partners regarding contraceptive requirements as listed for female patients who are WOCBP or pregnant.
  7. Able and willing to give written informed consent to join trial

Exclusion Criteria:

  1. Not deemed clinically suitable for resective brain surgery (e.g. because of failure to identify a single region of seizure onset in the neocortex, region is too extensive or the region overlaps with areas necessary for critical functions such as language), as confirmed by intracranial EEG investigations
  2. Vascular brain lesions or vascular malformations in area of planned resection
  3. Detection of active cancer or on systemic treatment for cancer
  4. Known or suspected HIV infection (confirmed by PCR test) and/or taking antiretroviral therapy
  5. Patient deemed medically unfit for anaesthesia and surgery
  6. Active, untreated psychiatric disease in the opinion of the treating clinician
  7. Concurrent and/or recent involvement in another clinical trial of an investigational medicinal product (within last 3 months)
  8. Females who are pregnant (confirmed by serum/urine ß-HCG) or actively breast-feeding
  9. Known allergies to excipients of lentiviral gene therapy
  10. Patient unlikely to cooperate with a 5-year follow-up; medical or psychological condition at the discretion of the investigator which would not permit compliance with the protocol or meaningful written informed consent
  11. Any other known condition which is assessed as an intolerable risk by the investigator upon inclusion in the trial

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    lentiviral gene therapy treatment (Intervention Arm)

    Arm Description

    Patients will receive a single dose of lentiviral gene therapy treatment administered once intracranially

    Outcomes

    Primary Outcome Measures

    Safety during the First Year (for adverse events related to lentiviral gene therapy only)
    Number and severity of all adverse events (graded using CTCAE v5.0) in patients deemed causally related to lentiviral gene therapy
    Safety during the First Year (for adverse events causally related to investigational surgical procedures only)
    Number and severity of all adverse events (graded using CTCAE v5.0) deemed causally related to any of the investigational surgical trial procedures required for vector administration

    Secondary Outcome Measures

    Long-Term Safety (for adverse events related to lentiviral gene therapy only)
    Number of serious adverse events (graded using CTCAE v5.0) in patients related to the lentiviral gene therapy
    Long-Term Safety (for adverse events causally related to investigational surgical procedures only)
    Number of serious adverse events (graded using CTCAE v5.0) in patients related to the investigational surgical procedures required for vector administration
    Clinical Indicators of Efficacy and Tolerability
    Seizure frequency and severity over preceeding 4 weeks
    Clinical Indicators of Efficacy and Tolerability
    Seizure frequency and severity (using IALE outcomes scale)
    Clinical Indicators of Efficacy and Tolerability
    Proportion of patients who have had surgical resection
    Cortical excitability
    Cortical excitability (assessed using TMS, EMG, and high-density EEG)

    Full Information

    First Posted
    October 6, 2020
    Last Updated
    May 12, 2023
    Sponsor
    University College, London
    Collaborators
    Medical Research Council
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04601974
    Brief Title
    Lentiviral Gene Therapy for Epilepsy
    Official Title
    Phase I/IIa, First-in-human, Open-label, Single-site Trial of In-vivo Lentiviral Engineered Potassium (K+) Channel (EKC) Gene Therapy for Refractory Epilepsy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2024 (Anticipated)
    Primary Completion Date
    September 2028 (Anticipated)
    Study Completion Date
    September 2032 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University College, London
    Collaborators
    Medical Research Council

    4. Oversight

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

    5. Study Description

    Brief Summary
    This is a phase I/IIa clinical trial investigating the safety of a lentiviral epilepsy gene therapy using an engineered potassium channel in patients with refractory epilepsy.
    Detailed Description
    Epilepsy affects about 1% of the population. One third of affected individuals continue to have seizures despite optimal medication. The only realistic prospect of seizure freedom, feasible in very few cases, is surgery to remove the brain area where seizures arise. Patients with refractory neocortical epilepsy who are being evaluated for surgical resection of the seizure focus will be invited to join the trial. The non-integrating lentiviral vector, which has been engineered to deliver an engineered potassium channel, will be administered via intracerebral infusion to the area scheduled for resection. The primary objective in this study is to test the safety of the lentiviral gene therapy treatment, including the surgical procedures required for vector administration. Secondary objectives will look at delayed onset adverse events and indicators of efficacy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Drug Resistant Epilepsy
    Keywords
    lentiviral gene therapy, brain, surgery, drug resistant epilepsy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    10 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    lentiviral gene therapy treatment (Intervention Arm)
    Arm Type
    Experimental
    Arm Description
    Patients will receive a single dose of lentiviral gene therapy treatment administered once intracranially
    Intervention Type
    Genetic
    Intervention Name(s)
    lentiviral gene therapy
    Intervention Description
    lentiviral gene therapy to treat drug resistant epilepsy
    Primary Outcome Measure Information:
    Title
    Safety during the First Year (for adverse events related to lentiviral gene therapy only)
    Description
    Number and severity of all adverse events (graded using CTCAE v5.0) in patients deemed causally related to lentiviral gene therapy
    Time Frame
    At 6 weeks, 3 months, 6 months and 12 months after trial treatment
    Title
    Safety during the First Year (for adverse events causally related to investigational surgical procedures only)
    Description
    Number and severity of all adverse events (graded using CTCAE v5.0) deemed causally related to any of the investigational surgical trial procedures required for vector administration
    Time Frame
    At 6 weeks, 3 months, 6 months and 12 months after trial treatment
    Secondary Outcome Measure Information:
    Title
    Long-Term Safety (for adverse events related to lentiviral gene therapy only)
    Description
    Number of serious adverse events (graded using CTCAE v5.0) in patients related to the lentiviral gene therapy
    Time Frame
    From 1 to 5 years after treatment
    Title
    Long-Term Safety (for adverse events causally related to investigational surgical procedures only)
    Description
    Number of serious adverse events (graded using CTCAE v5.0) in patients related to the investigational surgical procedures required for vector administration
    Time Frame
    From 1 to 5 years after treatment
    Title
    Clinical Indicators of Efficacy and Tolerability
    Description
    Seizure frequency and severity over preceeding 4 weeks
    Time Frame
    Measured at 6 weeks, 3 months, 6 months, and 12 months/1 year after trial treatment
    Title
    Clinical Indicators of Efficacy and Tolerability
    Description
    Seizure frequency and severity (using IALE outcomes scale)
    Time Frame
    Measured at 12 months/1 year, 2 years, 3 years, 4 years and 5 years after trial treatment
    Title
    Clinical Indicators of Efficacy and Tolerability
    Description
    Proportion of patients who have had surgical resection
    Time Frame
    at 3, 6, or 12 months, or at 2, 3, 4, and 5 years after trial treatment
    Title
    Cortical excitability
    Description
    Cortical excitability (assessed using TMS, EMG, and high-density EEG)
    Time Frame
    at 6 months after trial treatment (only for patients in TMS study)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: SCREENING/PRE-CONSENT: Female and male patients with refractory focal epilepsy Aged ≥ 18 years (no upper age limit but deemed medically fit for surgery with a life expectancy of at least 5 years) Patient lives within 1 hour of transfer to an acute neurosurgical unit Being considered for resective brain surgery (to remove the epileptogenic focus) based on first-stage preoperative assessments carried out as part of routine clinical care within 2 years of registration, showing: 4.1. Absence of vascular brain lesions or vascular malformations and/or cancer in the resection area (as confirmed on MRI) 4.2. Absence of active, untreated psychiatric disease in the opinion of the treating clinician (as confirmed by neuropsychiatric assessment) 4.3. Patient requires second-stage intracranial EEG investigations to be carried out via burr hole surgery to further assess eligibility for resective brain surgery PRE-REGISTRATION: Patient deemed clinically suitable for resective brain surgery (i.e. a single region of seizure onset in the neocortex has been identified, and it does not overlap with areas necessary for critical functions such as language), as confirmed by intracranial EEG investigations Patients who are women of childbearing potential (WOCBP), or male patients with female partners who are WOCBP or pregnant must agree to use highly effective methods of contraception from the time consent is signed until three months after treatment. Men (if applicable), must also advise their female partners regarding contraceptive requirements as listed for female patients who are WOCBP or pregnant. Able and willing to give written informed consent to join trial Exclusion Criteria: Not deemed clinically suitable for resective brain surgery (e.g. because of failure to identify a single region of seizure onset in the neocortex, region is too extensive or the region overlaps with areas necessary for critical functions such as language), as confirmed by intracranial EEG investigations Vascular brain lesions or vascular malformations in area of planned resection Detection of active cancer or on systemic treatment for cancer Known or suspected HIV infection (confirmed by PCR test) and/or taking antiretroviral therapy Patient deemed medically unfit for anaesthesia and surgery Active, untreated psychiatric disease in the opinion of the treating clinician Concurrent and/or recent involvement in another clinical trial of an investigational medicinal product (within last 3 months) Females who are pregnant (confirmed by serum/urine ß-HCG) or actively breast-feeding Known allergies to excipients of lentiviral gene therapy Patient unlikely to cooperate with a 5-year follow-up; medical or psychological condition at the discretion of the investigator which would not permit compliance with the protocol or meaningful written informed consent Any other known condition which is assessed as an intolerable risk by the investigator upon inclusion in the trial
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Senior Clinical Project Manager
    Phone
    +44(0)2031088954
    Email
    ekctrial@ucl.ac.uk

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    IPD Sharing Plan Description
    Data may be shared with other researchers who are working in the public and charitable sector (universities, research institutes) or commercial companies involved in health care research in the UK or overseas. Participant data will be fully anonymised prior to data sharing. This means there will be no way to link the data to the original data set, or to individual participants. Anonymisation will be done by the trial statistician. Data shared in this way will be protected by a contractual agreement put in place between UCL (the Sponsor) and any respective institution.

    Learn more about this trial

    Lentiviral Gene Therapy for Epilepsy

    We'll reach out to this number within 24 hrs