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|
| General |
| Study Status |
Delayed |
Application Number /
Requirement Number |
P150038 S006/ PAS001 |
| Date Original Protocol Accepted |
11/06/2020
|
| Date Current Protocol Accepted |
11/11/2022
|
| Study Name |
PAS Registry Study for ExAblate 4000
|
| Device Name |
ExAblate
|
| General Study Protocol Parameters |
| Study Design |
Comprehensive/Linked/RegistryBased Surveillance
|
| Data Source |
Sponsor Registry
|
| Comparison Group |
No Control
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| Analysis Type |
Descriptive
|
| Study Population |
Adult: At least 22 yrs
|
| Detailed Study Protocol Parameters |
| Study Objectives |
Prospective, multicenter, international single arm, observational post-approval registry study
|
| Study Population |
Single-arm study of male and female patients at least 30 years old who plan to be treated for TDPD using the Exablate Neuro System and who meet the specific enrollment criteria
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| Sample Size |
50 patients are planned for this registry study. From the protocol:
A total of 50 subjects will be enrolled. A t-test graph demonstrated that the power will be sufficient to determine any significant differences in long-term effectiveness at a=0.05. The graph showed that at 25 subjects, the number of subjects needed had plateaued. With an approximate average of an 8% dropout per year through Year 5, the remaining population is estimated to be approximately 30 subjects at year 5, which shows full power.
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| Key Study Endpoints |
From the protocol:
Safety Analysis
Safety will be evaluated through descriptive analysis of the incidence and severity of adverse events. Adverse events will be recorded and categorized according to severity, expectedness, and relationship to Exablate Neuro system thalamotomy procedure and/or disease progression. Results will be tabulated and reported as follows:
Post thalamotomy incidence and severity of adverse events (AEs).
Comparison of post thalamotomy incidence and severity adverse event rates to the prior Exablate study for ET (PMA #P150038), and TDPD earlier study (P150038/S006).
Comparison of post thalamotomy incidence and severity adverse
events rates to prior Deep Brain Stimulation (DBS) rates
Effectiveness Analysis
Effectiveness will be evaluated through descriptive analysis of ON medication CRST scores for tremor/motor, posture/rest, and level of
disability. Results will be presented as percent change from baseline to post thalamotomy study visits for all subjects where unilateral Exablate
thalamotomy was attempted.
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| Follow-up Visits and Length of Follow-up |
5 years
|
| Interim or Final Data Summary |
| Interim Results |
Safety Results
Table 5 below presents 31 adverse events in 13 of the 28 subjects. Fifteen subjects had no adverse events. Fourteen events are newly reported in this report. Of these 14, 5 were related to the thalamotomy procedure, and 9 were unrelated to the device or procedure. Additionally, of these 14 events, 4 were considered Mild, 4 were considered Moderate, and 6 were considered Severe. Of the 31 total adverse events, ten events were Mild in severity, ten events were Moderate, eleven events were Severe, and no events were Life Threatening. Twenty-one out of 31 adverse events were either transient (resolving within three days) or unrelated to the device or procedure. Nine events were Thalamotomy-related and one event was Procedure-related. Of all the reported events, no events were reported as Device-related.
Effectiveness Results:
Although the sample size is still small, the CRST generally improved from Baseline. The mean Tremor-Motor score improved from 14.6 to approximately 1-5 at during the follow-up period covering Month 3 through Year 3; the percent change of improvement was approximately 72-88% during this same period (Table 6 and Figure 1).The posture score is a sub-measure of the treated side Tremor Motor Score from the CRST Part A. Tremor as measured by posture showed improvement (Table 7 and Figure 2). The posture scores from Month 3 to Year 3 were approximately 0.4-0.9 with a Baseline of 2.6. The percent change from Baseline ranged from approximately 72% to 100% during this follow-up period. The Rest score is a sub-measure of the treated side Tremor Motor Score from the CRST Part A. Rest scores improved from a Baseline of 2.8 to a range of 0.0-0.8 at Months 3 through Year 3. Percent change from Baseline ranged from 74% to 100% during this follow-up period. The CRST Part C is an assessment of the impact of tremor on routine activities; speaking, eating, drinking, hygiene, dressing, writing, and working. The total Part C (average of each activity) measures the overall impact of tremor on daily activities. As can be seen in Table 9 and Figures 4a and 4b, although the Part is a broader measure of tremor impact, Part C Total score improved from 11.2 to a range of 2.6 – 6.3 at Month through Year 2 (percent change of 42-71%), but slightly increased from the respective Baseline scores of the 2 subjects who have reached the Year 3 timepoint (worsening of 4%). The improvement in tremor indicated by the CRST was also evident in the UPDRS Part III tremor scores. (Table 10 and Figure 5). The UPDRS Part III tremor scores were consistent with the CRST scores presented above. The Baseline mean score was 4.6 and follow up scores ranged from approximately 0.5 to 1.8 at Month 3 through Year 3 (percent change from Baseline of 63% to 90%).
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| Actual Number of Patients Enrolled |
28
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| Actual Number of Sites Enrolled |
8
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| Patient Follow-up Rate |
the expected subjects of Month 1, 3, 6, 12 are 28, 28, 22, and 19, respectively. The actual number of subjects completed the follow-up visits are 24 (86%), 22 (79%), 21 (95%), and 16 (84%).
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