Lentiviral Gene Therapy for Epilepsy

NCT04601974 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 18/0202
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Drug Resistant Epilepsy

Keywords

lentiviral gene therapy; brain; surgery; drug resistant epilepsy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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)

  From 1 to 5 years after treatment

• Long-Term Safety (for adverse events causally related to investigational surgical procedures only)

  From 1 to 5 years after treatment

• Clinical Indicators of Efficacy and Tolerability

  Measured at 6 weeks, 3 months, 6 months, and 12 months/1 year after trial treatment

• Clinical Indicators of Efficacy and Tolerability

  Measured at 12 months/1 year, 2 years, 3 years, 4 years and 5 years after trial treatment

• Clinical Indicators of Efficacy and Tolerability

  at 3, 6, or 12 months, or at 2, 3, 4, and 5 years after trial treatment

Study Arms (1)

lentiviral gene therapy treatment (Intervention Arm)

EXPERIMENTAL

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

Genetic: lentiviral gene therapy

Interventions

lentiviral gene therapy GENETIC

lentiviral gene therapy to treat drug resistant epilepsy

lentiviral gene therapy treatment (Intervention Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Medical Research Council: collaborator

MeSH Terms

Conditions

Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Senior Clinical Project Manager

CONTACT

+44(0)2031088954; ekctrial@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 26, 2020
• Study Start: September 1, 2024
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2032
• Last Updated: May 15, 2023

Record last verified: 2023-05