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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P150038 / PAS001 |
| Date Original Protocol Accepted |
09/29/2016
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| Date Current Protocol Accepted |
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| Study Name |
Long Term PAS
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| Device Name |
EXABLATE
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| Clinical Trial Number(s) |
NCT01827904
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
Device Subjects Serve as Own Control
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| Analysis Type |
Analytical
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| Detailed Study Protocol Parameters |
| Study Objectives |
Long-term prospective, observational clinical trial to follow device related safety, and long term effectiveness and quality of life for subjects previously treated with the ExAblate Neuro under the IDE G120246.
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| Study Population |
The study population includes those patient that have undergone the ExAblate Neuro thalamotomy treatment for the treatment of medication refractory Essential Tremor under G120246.
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| Sample Size |
There are three main cohorts from the original pivotal study that will be included in this long term follow-up study:
1. The main IDE (G120246) study population that was randomized, N=56.
2. The cross-over population, N=21
3. The population that was part of the Continued Access study, N=59
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| Key Study Endpoints |
Safety: Safety of ExAblate will be determined by an evaluation of the incidence and severity of device / treatment related complications from the treatment day visit through ALL study follow ups through Year 5. Adverse events (type, frequency, severity) are expected to be similar to those of previous studies using ExAblate TcMRgFUS for Thalamotomy
Effectiveness: Primary effectiveness will be assessed using the Clinical Rating Scale for Tremor (CRST) as scored by the site neurologist. Secondary effectiveness will be assessed by using the Quality of Life inn Essential Tremor (QUEST) Questionnaire.
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Interim Results |
The safety profile of the Exablate thalamotomy procedure continues to maintain a favorable and relatively benign safety profile as demonstrated by the following:
• No related adverse events were reported in either the Exablate Pivotal Cohort or the Exablate Crossover Cohort after Month 3.
• The safety profile in the Exablate Continued Access Cohort is very similar and shows a similar favorable and relatively benign safety profile.
The Primary and Secondary Endpoints of the Pivotal Study were calculated in similar manner for each of the other cohorts and presented in both tabular format and graphically as shown in the tables and figures below. To easily compare the differences between cohorts, these data are compared graphically in a bar chart to demonstrate that the effect observed in the pivotal portion is similar across cohorts and durable over time
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| Actual Number of Patients Enrolled |
61
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| Actual Number of Sites Enrolled |
8
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| Patient Follow-up Rate |
34 subjects were screen failed for the reasons such as SDR3 disqualification (13 subjects), Personal Health issues/ claustrophobia/ anxiety/ kyphosis (7 subjects), Cognitive impairment (4 subjects), Misdiagnosed-had PD (2 subjects), and other reasons
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| Final Safety Findings |
The main safety data were presented in the Attachment 004 (P150038/R024) which included Appendix 1 with the Listing of Adverse Events inclusive of those reported in previous PAS reports. In addition, Attachment 003 presented the Ongoing AE Survival Tables (not shown) stratified by follow-up year, body system, and other groupings.
The AE profile of the ET002CA cohort was characterized by Insightec as favorable, with no unexpected AEs.
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| Final Effect Findings |
The site assessor scoring across all time points was used for consistency through long-term follow-up visits. The Primary and Secondary Endpoints were calculated in a manner similar to the Pivotal Study and presented in tabular and graphic formats.
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| Study Strengths & Weaknesses |
The main strength of this Continued Access PAS is the 5-year follow-up duration including more than 95% of the original population at the 12 Month visit. Twenty-six subjects completed the 5 Year visit despite COVID-19 pandemic. With respect to effectiveness, the duration of tremor/motor function, posture and activities of daily living were sustained through year 5.
Regarding safety, no new adverse events were observed during long term follow-up that were related to the device, procedure or thalamotomy. Furthermore, some of the unresolved events at the end of 12 Month follow-up continued to resolve with time. All events were followed using the worst severity ever reported during the study.
With respect to weaknesses of the study, the continued access study was performed using the original independent comparator. However, the study design was the same as the pivotal trial with respect to the test arm and the results were similar (Figure 10).
Additionally, the study was performed as a unilateral procedure and was performed on the subject’s tremor dominant arm. While some patients might benefit from bilateral treatment, clinically meaningful improvements were observed in the unilateral side that permitted subjects to show improvement in their long-term activities of daily living
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| Recommendations for Labeling Changes |
For this population of subjects diagnosed with idiopathic ET with medication-refractory tremor, the Exablate Neuro treatment is a safe and effective treatment for their Essential Tremor. The result from the pivotal study showed that the treatment is efficacious and safe; most of the adverse events were mild or moderate in severity. Similarly, the data from the Continued Access study with 5-year long-term follow-up results continues to support the reasonable assurance of device safety and effectiveness when used in accordance with the indications for use.
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