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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05947656




Registration number
NCT05947656
Ethics application status
Date submitted
20/06/2023
Date registered
17/07/2023
Date last updated
31/05/2024

Titles & IDs
Public title
Evaluation of the NaviFUS System in Drug Resistant Epilepsy
Scientific title
An Open-label, Non-randomized, Single-arm Pilot Study to Evaluate the Safety and Efficacy of Multiple Pulsed Focused Ultrasound Treatment in Patients With Drug Resistant Temporal Lobe Epilepsy
Secondary ID [1] 0 0
GNIA22-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy, Temporal Lobe 0 0
Drug Resistant Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - NaviFUS System

Experimental: Cohort 1 - 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.

Experimental: Cohort 2 - 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.


Treatment: Devices: NaviFUS System
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).
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to 3 months after the last treatment session
Primary outcome [2] 0 0
Incidence of treatment discontinuation due to AEs and SAEs
Timepoint [2] 0 0
Up to 3 months after the last treatment session
Primary outcome [3] 0 0
Incidence of clinically significant abnormal findings from physical and neurologic examinations
Timepoint [3] 0 0
Up to 3 months after the last treatment session
Primary outcome [4] 0 0
Incidence of clinically significant abnormal vital sign measurements, and abnormal vital signs reported as AEs and SAEs
Timepoint [4] 0 0
Up to 3 months after the last treatment session
Primary outcome [5] 0 0
Incidence of 12-lead electrocardiogram (ECG) with clinically significant abnormal findings
Timepoint [5] 0 0
Up to 3 months after the last treatment
Primary outcome [6] 0 0
Incidence of Magnetic Resonance Imaging (MRI) with clinically significant abnormal findings
Timepoint [6] 0 0
Up to 3 months after the last treatment session
Primary outcome [7] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Boston Naming Test-Second Edition (BNT-2)
Timepoint [7] 0 0
Up to 3 months after the last treatment session
Primary outcome [8] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Auditory Naming Test (ANT)
Timepoint [8] 0 0
Baseline Visit and 3 months after the last treatment session
Primary outcome [9] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Sentence Repetition Test (SRT)
Timepoint [9] 0 0
Baseline Visit and 3 months after the last treatment session
Primary outcome [10] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Controlled Oral Word Association Test (COWAT)
Timepoint [10] 0 0
Baseline Visit and 3 months after the last treatment session
Primary outcome [11] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Wechsler Memory Scale-4 (WMS-4)
Timepoint [11] 0 0
Baseline Visit and 3 months after the last treatment session
Primary outcome [12] 0 0
Clinically significant changes in cognitive functions from baseline assessed by Rey Auditory Verbal Learning Test (RAVLT)
Timepoint [12] 0 0
Baseline Visit and 3 months after the last treatment session

Eligibility
Key inclusion criteria
1. Diagnosis of drug resistant temporal lobe epilepsy (TLE)

2. Patients must experience at least six (6) observable seizures over the 60-day
baseline, each on a separate day.

3. Patients have focal-onset seizures with or without secondary generalization.

4. Patients have had at least 24 hours video-electroencephalography (EEG) monitoring and
comprehensive epilepsy evaluation confirming TLE.

5. Seizure medication treatment is anticipated to remain stable during the trial, except
for rescue medicines or occasional extra doses of ongoing medicines, as required.

6. 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.

7. 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have primary generalized epilepsy or non-epileptic seizures in the last
two (2) years.

2. 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.

3. Patients who have experienced tonic-clonic status epilepticus in the three (3) months
leading up to enrollment in the study.

4. Presence of devices including but not limited to cardiac pacemaker, implantable
cardioverter-defibrillator (ICD), permanent medication pumps, cochlear implants,
responsive neurostimulator (RNS) or deep brain stimulation (DBS). Vagus nerve
stimulators (VNS) do not represent an exclusion criterion, but settings should be
stable throughout the trial.

5. Patients with clips or other metallic implanted objects in the FUS exposure path,
except shunts.

6. 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.

7. 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.

8. History of intracranial hemorrhage.

9. History of multiple strokes, or a stroke within the six (6) months prior to Screening.

10. Patients with intracranial aneurysms requiring treatment or arterial venous
malformations (AVMs) requiring treatment at any time.

11. 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.

12. 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.

13. 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).

14. Patients who are not able or willing to tolerate the required prolonged stationary
semi-supine position during treatment.

15. 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.

16. 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.

17. Patients who have received radiofrequency thermocoagulation (RFTC) within two (2)
months of Screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genovate-NaviFUS (Australia) Pty Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genovate Biotechnology Co., Ltd.,
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
NaviFUS Corporation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05947656
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Terrence O'Brien, Prof.
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Caitlin Roberts, Ms.
Address 0 0
Country 0 0
Phone 0 0
+61 3 9076 2598
Fax 0 0
Email 0 0
cai.roberts@alfred.org.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05947656