Evaluation of the NaviFUS System in Drug Resistant Epilepsy

NCT05947656 | Recruiting

• 1 other identifier: GNIA22-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Participants with drug-resistant epilepsy (DRE) enrolled in this study will receive focused ultrasound (FUS) treatment with the NaviFUS System, guided by the neuronavigation system to evaluate the safety and efficacy of using NaviFUS System. During the treatment, the FUS will electronically scan and target to the assigned zones on one or both of the hippocampi. The study consists of a 60-day screening period for baseline observation prior to treatment, a FUS treatment period of 2 weeks for Cohort 1 or 3 weeks for Cohort 2 with 2 FUS treatments per week using the NaviFUS System, and a safety follow-up period of 81 days.

Conditions

Epilepsy, Temporal Lobe; Drug Resistant Epilepsy

Keywords

Focused Ultrasound; Drug Resistant Temporal Lobe Epilepsy; Temporal Lobe Epilepsy

Outcome Measures

Primary Outcomes (12)

• Incidence, nature and severity of adverse events (AEs), serious adverse events (SAEs) and AE of special interest (seizures, headaches, mental state changes, language and memory changes, lethargy/fatigue, and nausea)

  This outcome will be assessed through the review of medical records and participant self-reporting in seizure diary.

  Up to 3 months after the last treatment session

• Incidence of treatment discontinuation due to AEs and SAEs

  Up to 3 months after the last treatment session

• Incidence of clinically significant abnormal findings from physical and neurologic examinations

  Up to 3 months after the last treatment session

• Incidence of clinically significant abnormal vital sign measurements, and abnormal vital signs reported as AEs and SAEs

  Up to 3 months after the last treatment session

• Incidence of 12-lead electrocardiogram (ECG) with clinically significant abnormal findings

  Up to 3 months after the last treatment

• Incidence of Magnetic Resonance Imaging (MRI) with clinically significant abnormal findings

  This outcome will be measured at Baseline Visit and 3 months after the last treatment session.

  Up to 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Boston Naming Test-Second Edition (BNT-2)

  BNT-2 is a 60-item/picture test to assess the ability to name common objects, with scores ranging from 0 to 60. Higher scores indicate better naming ability.

  Up to 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Auditory Naming Test (ANT)

  ANT is a 50-item test requiring participants to name a specific item to a description, with scores ranging from 0 to 50. Higher scores indicate better naming ability.

  Baseline Visit and 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Sentence Repetition Test (SRT)

  SRT tests immediate memory for sentences of increasing length (1-26 syllables), with scores ranging from 0 to 22. Higher scores indicate better performance.

  Baseline Visit and 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Controlled Oral Word Association Test (COWAT)

  COWAT is an oral fluency test in which the participant is required to make verbal associations to different letters of the alphabet by saying as many words as they can think of beginning with a given letter. Greater number of words produced indicates better performance on the test.

  Baseline Visit and 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Wechsler Memory Scale-4 (WMS-4)

  WMS-IV measures the ability to learn and remember information presented verbally and visually, with scores ranging from 60 to 140 (mean = 100; standard deviation = 15). Higher scores indicate better performance.

  Baseline Visit and 3 months after the last treatment session

• Clinically significant changes in cognitive functions from baseline assessed by Rey Auditory Verbal Learning Test (RAVLT)

  RAVLT is a test using a 15-word list to assess non-verbal learning and memory, with scores ranging from 0 to 15. Higher scores indicate better performance.

  Baseline Visit and 3 months after the last treatment session

Other Outcomes (8)

• Exploratory outcome 1: Change in seizure frequency after FUS treatment compared to baseline

  From Baseline Visit until 3 months after the last treatment session

• Exploratory outcome 2: Responder rate (defined as at least 50% seizure reduction)

  From Baseline Visit until 3 months after the last treatment session

• Exploratory outcome 3: Percentage change in days seizure-free

  From Baseline Visit until 3 months after the last treatment session

Study Arms (2)

Cohort 1

EXPERIMENTAL

Eligible patients in Cohort 1 will receive two (2) FUS treatments per week for two (2) weeks on Day 1, 4, 8 and 11, followed by three (3) safety follow-up visits on Day 36, 64 and 92.

Device: NaviFUS System

Cohort 2

EXPERIMENTAL

Eligible patients in Cohort 2 will receive two (2) FUS treatments per week for three (3) weeks on Day 1, 4, 8, 11, 15 and 18, followed by three (3) safety follow-up visits on Day 43, 71 and 99.

Device: NaviFUS System

Interventions

NaviFUS System DEVICE

NaviFUS System (Neuronavigation-Guided Focused Ultrasound System) is a new non-invasive device, which uses the neuronavigation principle to guide focused ultrasound (FUS) energy precisely delivering through the skull to selected brain tissues without surgery in real-time. In this clinical study, the NaviFUS System is intended to deliver low intensity FUS to generate neuromodulation effects on a predetermined treatment region (one or both of the hippocampi which are associated with seizure), for the treatment for drug-resistant temporal lobe epilepsy (TLE).

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Diagnosis of drug resistant temporal lobe epilepsy (TLE)
• Patients must experience at least four (4) observable seizures over the 60-day baseline, each on a separate day.
• Patients have focal-onset seizures with or without secondary generalization.
• Patients have had at least 24 hours video-electroencephalography (EEG) monitoring and comprehensive epilepsy evaluation confirming TLE.
• Seizure medication treatment is anticipated to remain stable during the trial, except for rescue medicines or occasional extra doses of ongoing medicines, as required.
• Patients should be capable of and willing to completing assessments and neuropsychological testing in English either alone or with the help of the study partner (where appropriate), per local guidelines. A study partner is a carer or family member of the patient.
• Patients and study partner (if applicable) who in the Investigator's opinion are reliable and able to use the seizure diary to record seizure throughout the study and are willing to comply with study procedures and visits.

You may not qualify if:

• Patients who have primary generalized epilepsy or non-epileptic seizures in the last two (2) years.
• More than two (2) seizure onset zones (foci) (except bitemporal foci) or unknown likely site of seizure onset, as determined by usual clinical, electroencephalography (EEG) and imaging practice.
• Patients who have experienced tonic-clonic status epilepticus in the three (3) months leading up to enrollment in the study.
• Patients with clips or other metallic implanted objects in the FUS exposure path, except shunts.
• Patients with more than thirty percent (30%) of the skull area traversed by the sonication pathway covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp at Screening.
• Patients who have a medical or surgical history of severe systemic disease(s), such as (but not limited to) coronary artery disease, myocardial infarct, progressive heart failure, uncontrolled hypertension or abnormal ECG, severe pulmonary hypertension (pulmonary artery pressure \> 90 mmHg), chronic obstructive pulmonary disease (COPD), adult respiratory distress syndrome, hepatic and renal insufficiency (ALT or AST 3 times above normal range; serum creatinine \> 1.3 mg/dL), diabetic patients with poor control of blood sugar (HbA1c \> 8.5 %) at Screening.
• History of intracranial hemorrhage.
• History of multiple strokes, or a stroke within the six (6) months prior to Screening.
• Patients with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment at any time.
• Presence of central nervous system (CNS) disease(s) other than epilepsy including but not limited to infections of the CNS (e.g., syphilis, Lyme disease, borreliosis, viral or bacterial meningitis/encephalitis, human immunodeficiency virus \[HIV\] encephalopathy), cerebral vascular disease, Parkinson's disease, traumatic brain injury, alcoholic encephalopathy within three (3) years prior to Screening.
• Patients with concurrent major psychiatric disorder, such as schizophrenia or bipolar disorder, severe depression, active suicidal ideation, active psychosis (excluding time-limited postictal psychosis) or psychiatric hospitalization within one (1) year before Screening.
• Prior diagnosis of cancer within the past two (2) years and evidence of continued malignancy within the past two (2) years (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with normal prostate-specific antigens post resection).
• Patients who are not able or willing to tolerate the required prolonged stationary semi-supine position during treatment.
• Inability to tolerate MRI procedures or contraindication to MRI (e.g. claustrophobia, too large for MRI scanner), including, but not limited to, presence of pacemakers (with the exception of MRI-safe pacemakers), aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or other areas of the body that would contraindicate an MRI scan.
• Patients who had major surgery six (6) weeks before study enrollment or who are not fully recovered from a surgical procedure or with planned surgery during study period or within fourteen (14) days thereafter.

Sponsors & Collaborators

• Genovate-NaviFUS (Australia) Pty Ltd.: lead
• Genovate Biotechnology Co., Ltd.,: collaborator
• NaviFUS Corporation: collaborator

Study Sites (1)

The Alfred

Melbourne, Victoria, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Epilepsy, Temporal Lobe; Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Epilepsies, Partial; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Terrence O'Brien, Prof.

  The Alfred

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caitlin Roberts, Ms.

CONTACT

+61 3 9076 2598; cai.roberts@alfred.org.au

Jack Germaine, Mr.

CONTACT

+61 3 9076 2029; j.germaine@alfred.org.au

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of two (2) cohorts. Nine (9) eligible patients will be enrolled to each cohort. The only difference between the two cohorts is the overall number of weeks of treatment (2 weeks for Cohort 1 vs. 3 weeks for Cohort 2). The study investigator will advise on which cohort the patients are enrolling into as it will depend on when the patients enter the study. The safety monitoring committee (SMC) will review all safety data for Cohort 1 and confirm that it is safe to proceed with the study before the study treatment for Cohort 2 can start.

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 17, 2023
• Study Start: October 2, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)