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| General |
| Study Status |
Delayed |
Application Number /
Requirement Number |
P150038 S014/ PAS001 |
| Date Original Protocol Accepted |
06/30/2022
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| Date Current Protocol Accepted |
07/29/2022
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| Study Name |
ExAblate Neuro PAS
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| Device Name |
Exablate Model 4000 Type 1.0 and 1.1 System (“Exablate Neuro”)
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| Clinical Trial Number(s) |
NCT03319485
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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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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| Detailed Study Protocol Parameters |
| Study Objectives |
The objectives of this Registry are:
Collect the safety and effectiveness data of performing pallidotomy for Parkinson’s Disease Motor Complications using the Exablate Neuro system through Year 5.
This is a post-approval registry which is required by the approval under PMA P150038/S014 for the Exablate® Model 4000 (Exablate Neuro) Type 1.0 and Type 1.1 for unilateral pallidotomy in the treatment of advanced, idiopathic Parkinson’s disease with medication-refractory moderate to severe motor complications as an adjunct to Parkinson’s disease medication treatment. This protocol will enroll approximately 60 new subjects as Cohort 2. Cohort 1 includes the long-term follow-up from the G170237 IDE which will continue to Year 5
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| Study Population |
The population enrolled in this registry will be comprised of male and female patients that plan to be treated using the Exablate Neuro system for advanced, idiopathic Parkinson’s disease with medication-refractory moderate to severe motor complications
1. Men and women, age 30 years and older
2. Subject undergoing a planned an Exablate procedure for their Parkinson’s Disease with Motor Complications per local institution standard of care.
3. Subject is willing to cooperate with the Registry requirements including compliance with the regimen and completion of all Registry visits
4. Subject has signed and received a copy of the approved informed consent form
This is a single arm study, which is no comparison group.
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| Sample Size |
The proposed registry will enroll 60 subjects and will be conducted at approximately 10 centers worldwide.
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| Key Study Endpoints |
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 pallidotomy procedure and/or disease progression. Results will be tabulated and reported as follows:
• Post pallidotomy incidence and severity of adverse events (AEs).
• Comparison of post pallidotomy incidence and severity of adverse event rates to the prior Exablate Registry for PD (PMA #P150038/S014).
• Comparison of post pallidotomy incidence and severity of adverse events rates to Deep Brain Stimulation (DBS) rates as reported in the literature
Primary Effectiveness will be evaluated through a Responder analysis. Responder is defined as the patient reaching a minimally clinically significant difference on:
• UDysRS Objective Assessment ON Meds, without clinically significant worsening of MDS-UPDRS Part III OFF Meds aggregated extremity score for treated side
• 2) MDS-UPDRS Part III OFF Meds Motor Exam on the treated side, without clinically significant worsening of UDysRS Objective Assessment ON meds
Minimally clinically important difference for this Registry is defined as follows:
• Control of dyskinesia will be captured using the UDysRS Objective assessment ON meds. A Responder will be identified as Improvement by more than 3 points (lower score than Baseline) and Worsening will be identified as more than 3 points higher (compared to Baseline).
• Control of bradykinesia will be captured by Off meds state MDS-UPDRS Part III aggregated extremity questions for treated side. A Responder will be identified as at least 3 or more points Improvement (lower score than Baseline). Worsening is defined as at least 4 points or more higher (compared to Baseline) Additional Data.
Additional data, including but not limited to, demographics, change from baseline to all Registry visits of each MDS-UPDRS (Parts I, II, III OFF, IV), UDysRS, CGIC, PGIC, patient satisfaction questionnaire may be compiled.
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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
PD006: Table 4b presents 13 adverse events in nine subjects newly reported this period. Eight events were mild or moderate in severity, none were reported as severe, and five were reported as life threatening. Eleven events were reported as unrelated to the device or procedure by the investigators. Two were reported as Parkinson’s disease related. The five-life threatening adverse events were also reported as SAEs and are discussed.
PD015: As of October 1, 2024, 2 out of 6 subjects (2/6 = 33%) have experienced at least one adverse event, and 4 out of 6 subjects (67%) have experienced no adverse events (Table 4). As shown in Table 5, 1 adverse event reported was mild and 1 was moderate. There have been 0 serious adverse events reported.
Effectiveness Results:
Description (Extended Follow-up of the PD006 IDE cohort)
• Responder analysis: N.A.
1) UDysRS Objective Assessment ON Meds, without clinically significant worsening of MDS-UPDRS Part III OFF Meds aggregated extremity score for treated side
Or
• 2) MDS-UPDRS Part III OFF Meds Motor Exam on the treated side, without clinically significant worsening of UDysRS Objective Assessment ON meds
Control of dyskinesia will be captured using the UDysRS Objective assessment ON meds. A Responder will be identified as Improvement by more than 3 points (lower score than Baseline) and Worsening will be identified as more than 3 points higher (compared to Baseline)
Control of bradykinesia will be captured by Off meds state MDS-UPDRS Part III aggregated extremity questions for treated side. A Responder will be identified as at least 3 or more points Improvement (lower score than Baseline). Worsening is defined as at least 4 points or more higher (compared to Baseline)
• MDS-UPDRS, Parts II Daily living: Figure 4a, 4b and Table-9
Off-medication, MDS-UPDRS part III (Subjects should enter the clinic in the off state for assessment with no PD medications taken after midnight the previous night, or at least a minimum of 4 hours since last dose.): Figure 1a and Table -6
• On-medication, UDYSRS Objective Impairment (On Meds) Figures 2a and 2b, Table 7
• MDS-UPDRS, Part IV: Figures 3a and 3b, and Table 8
• Unified Dyskinesia Rating Scale: Figures 5a and 5b, Table 10
• Patient Global Impression of Change: Figure 8 and Table 13
• Clinician Global Impression of Change: Figure 7 and Table 12
• Patient Treatment Satisfaction Questionnaire: Table 14
• EQ-5D-5L: N.A. Def
• WPAI-GH: N.A. Def
• MDS-UPDRS, Parts I-II: N.A. Def
Description (New enrollment PD015 cohort): N.A.
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| Actual Number of Patients Enrolled |
A total of 166 subjects were recruited for the trial. Of these potential study candidates, 72 subjects were considered screen fails and 94 subjects were randomized. Of the 94 subjects randomized, 92 subjects (68 Exablate, 24 Sham) were considered treated (received at least 1 sonication).
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| Actual Number of Sites Enrolled |
19
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| Patient Follow-up Rate |
The PAS annual report continues the Year 2-5 long term follow-up (FU). Subject disposition for the Main Group is presented in Table 3b. Fifty-four subjects were ongoing from Month 12 and continued follow up in this PAS. Since the Month 12 visit, 24 subjects exited the Main Exablate group of the PAS study before completing the Year 5 visit (Table 3). One subject, 115-013, was previously reported as lost to follow-up but subsequently returned to the site to complete the Year 4 visit.
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