Drug Resistant EpilepsyPhase 1/2NCT04601974
Lentiviral Gene Therapy for Epilepsy
A Phase 1/2 study testing lentiviral gene therapy in people with Drug Resistant Epilepsy, run by University College, London.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Resistant Epilepsy
- What is being tested?
- lentiviral gene therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Sep 2024to Sep 2032
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
Read the 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.
- Conditions
- Drug Resistant Epilepsy
- Being tested
- lentiviral gene therapy
- Keywords
- lentiviral gene therapy, brain, surgery, drug resistant epilepsy
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lentiviral gene therapyGenetic
lentiviral gene therapy to treat drug resistant epilepsy
| Study group | Role | What they receive |
|---|---|---|
| lentiviral gene therapy treatment (Intervention Arm) | Experimental | Patients will receive a single dose of lentiviral gene therapy treatment administered once intracranially Receives: Genetic: lentiviral gene therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At 6 weeks, 3 months, 6 months and 12 months after trial treatment
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
Measured: At 6 weeks, 3 months, 6 months and 12 months after trial treatment
Secondary outcomes (6)
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
Measured: From 1 to 5 years after treatment
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
Measured: From 1 to 5 years after treatment
Clinical Indicators of Efficacy and Tolerability
Seizure frequency and severity over preceeding 4 weeks
Measured: Measured at 6 weeks, 3 months, 6 months, and 12 months/1 year after trial treatment
Clinical Indicators of Efficacy and Tolerability
Seizure frequency and severity (using IALE outcomes scale)
Measured: Measured at 12 months/1 year, 2 years, 3 years, 4 years and 5 years after trial treatment
Clinical Indicators of Efficacy and Tolerability
Proportion of patients who have had surgical resection
Measured: at 3, 6, or 12 months, or at 2, 3, 4, and 5 years after trial treatment
Cortical excitability
Cortical excitability (assessed using TMS, EMG, and high-density EEG)
Measured: at 6 months after trial treatment (only for patients in TMS study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2020
- Study startSep 2024 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Resistant EpilepsyStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04601974
- Sponsor's protocol ID
- 18/0202
- Status last verified
- May 2023
- First submitted
- 6 Oct 2020
- Last updated
- 15 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04601974
- Acronym / sponsor ID
- 18/0202
- Conditions
- Drug Resistant Epilepsy
- Keywords
- lentiviral gene therapy, brain, surgery, drug resistant epilepsy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- Sep 2024 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2032 (estimated)
- First posted
- 26 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| lentiviral gene therapy treatment (Intervention Arm) | Experimental | Genetic: lentiviral gene therapyPatients will receive a single dose of lentiviral gene therapy treatment administered once intracranially |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lentiviral gene therapylentiviral gene therapy to treat drug resistant epilepsy | Genetic | lentiviral gene therapy treatment (Intervention Arm) |
Primary outcome
Safety during the First Year (for adverse events related to lentiviral gene therapy only)
Time frame: At 6 weeks, 3 months, 6 months and 12 months after trial treatment
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)
Time frame: At 6 weeks, 3 months, 6 months and 12 months after trial treatment
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
6 secondary outcomes
Long-Term Safety (for adverse events related to lentiviral gene therapy only)
Time frame: From 1 to 5 years after treatment
Long-Term Safety (for adverse events causally related to investigational surgical procedures only)
Time frame: From 1 to 5 years after treatment
Clinical Indicators of Efficacy and Tolerability
Time frame: Measured at 6 weeks, 3 months, 6 months, and 12 months/1 year after trial treatment
Clinical Indicators of Efficacy and Tolerability
Time frame: Measured at 12 months/1 year, 2 years, 3 years, 4 years and 5 years after trial treatment
Clinical Indicators of Efficacy and Tolerability
Time frame: at 3, 6, or 12 months, or at 2, 3, 4, and 5 years after trial treatment
Cortical excitability
Time frame: at 6 months after trial treatment (only for patients in TMS study)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2023.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing lentiviral gene therapy in people with Drug Resistant Epilepsy, run by University College, London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Senior Clinical Project Manager (+44(0)2031088954, ekctrial@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety during the First Year (for adverse events related to lentiviral gene therapy only) (time frame: At 6 weeks, 3 months, 6 months and 12 months after trial treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2023; AzTrials last refreshed its copy on 1 Nov 2026.