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| General |
| Study Status |
Delayed |
Application Number /
Requirement Number |
P150038 S006/ PAS001 |
| Date Original Protocol Accepted |
11/06/2020
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| Date Current Protocol Accepted |
11/11/2022
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| Study Name |
PAS Registry Study for ExAblate 4000
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| Device Name |
ExAblate
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| General Study Protocol Parameters |
| Study Design |
Comprehensive/Linked/RegistryBased Surveillance
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| Data Source |
Sponsor Registry
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| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
Prospective, multicenter, international single arm, observational post-approval registry study
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| 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
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| Interim or Final Data Summary |
| Interim Results |
Safety Results
[7] events in eleven of the 20 subjects. Nine subjects had no adverse events (total subjects, 20). Four of the events, all unrelated to the procedure or device, were new this reporting period (Rotator cuff tear, Fracture humerus, Atrial fibrillation and Stroke). Five events in four subjects were Mild in severity, six events were Moderate, six events in five subjects were Severe, three of which were reported in the previous semiannual reports (three new severe events were Unrelated to the study), and no events were Life Threatening. There were three new Severe AEs in this reporting period, all were Unrelated to the study of the device. Eleven out of 17 adverse events were either transient, resolving within three days or unrelated to the device or procedure. Three events were Thalamotomy related. The event of severe imbalance issues was reported five days post treatment and was reported in a previous semiannual report (as “Ambulatory Issues”). Of all the reported events, no events were reported as Device-related. There was a transient sonication related pain.
Effectiveness Results
Although the sample size is still small, the CRST generally improved from Screening baseline. The mean Tremor-Motor score improved from 13.6 to 2.5-2.0 at Months 3-12; percent change improved 83-86% (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 (Tables 7 & 8, and Figures 2 & 3). The posture scores from Month 3 to Month 12 were about 0.6 with a Baseline of 2.7 and the percent change from Baseline ranged from 76% to 84%. 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 3 to 0.5 – 0.2 at Months 3 to 12. Percent change from Baseline ranged from 86% to 94%. 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 10.2 to 4.1 – 4.2 at months 3-12 (Figure 4b). Percent change at Months 3-12 ranged from 65-44%. The improvement in tremor indicated by the CRST was also evident in the UPDRS Part III tremor scores. (Table 10 and Figures 5). The UPDRS Part III tremor scores were consistent with the CRST scores presented above. The Baseline mean score was 4.9 and follow up scores ranged from about 0.7 to 1. Follow up percent change from Baseline ranged from 73% to 76%.
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| Actual Number of Patients Enrolled |
20
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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 20, 18, 16, and 11, respectively. The actual number of subjects completed the follow-up visits are 19, 15, 16, and 10.
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