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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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| 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
(Extended Follow-up of the PD006 IDE cohort)
The DSMB reviewed the safety information (AEs and SAEs) presented in this report on June 27, 2023, and recommended continuing the study as is.
In the Exablate Main Group, two pallidotomy related adverse events were previously reported as ongoing at Month 12 (Table 4a); moderate dysarthria and increased salivation/drooling. However, the salivation/drooling resolved within a month prior to PMA review and approval. Thus, this event was not ongoing after the 12 Month visit and was deleted herein from Table 4a. The subject reporting dysarthria (115011) developed sepsis from a shoulder infection, died (see SAE narrative) and there will be no follow-up resolution. There were no ongoing procedure-related events as of Month 12.
Table 4b presents 19 adverse events in 11 subjects reported post-PMA. Fifteen events were mild or moderate in severity and four were reported as severe. Seven events out of the 19 are newly reported for this reporting period. All seven events were reported as unrelated to the device or procedure by the investigators. One event out of the seven was reported as Severe: back pain. Twelve out of the 19 events were reported in the previous reporting period.
Narratives for three SAEs in two subjects are presented below in Section 5.2.2.
(New enrollment PD015 cohort)
One subject has been enrolled and has reached the 3-month follow-up timepoint. Results will begin to be analyzed for efficacy once a minimum of five subjects have reached at least the 3-month follow-up timepoint. Safety of the study as of June 30, 2023 is discussed below; briefly, there has been 1 Adverse Event reported which was moderate in severity and Transient.
Effectiveness Results
(Extended Follow-up of the PD006 IDE cohort)
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 |
Randomization in PD006 was 3:1, Exablate:Sham Control. For analyses there were initially 68 subjects in the PD006 Main Group and 22 subjects in the PD006 Crossover Group. The PMA approval letter is dated October 29, 2021, and the data through Month 12 was reviewed in the PMA (P150038/S014). In this report Main and Crossover concern the long-term (post PMA/Month 12) follow-up of subjects continuing in the study.
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| Actual Number of Sites Enrolled |
19
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| Patient Follow-up Rate |
Subject disposition for the Main Group is presented in Table 3. The PAS annual report is for the Year 2-5 follow-up (FU). All Month 12 follow up was completed for the main Exablate group. Fifty-four subjects were ongoing from Month 12 and continued follow up in this PAS (Table 3, Year 2 Continuing LTFU).
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