Lentiviral Gene Therapy for Epilepsy

NCT ID: NCT04601974

Last Updated: 2023-05-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2032-09-30

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.

Conditions

Drug Resistant Epilepsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lentiviral gene therapy treatment (Intervention Arm)

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

Group Type: EXPERIMENTAL

lentiviral gene therapy

Intervention Type: GENETIC

lentiviral gene therapy to treat drug resistant epilepsy

Interventions

lentiviral gene therapy

lentiviral gene therapy to treat drug resistant epilepsy

Intervention Type: GENETIC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council

OTHER_GOV

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Senior Clinical Project Manager

Role: CONTACT

ekctrial@ucl.ac.uk

+44(0)2031088954

Other Identifiers

18/0202

Identifier Type: -

Identifier Source: org_study_id