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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
S014 (PD006)
1. In the Exablate Main Group, one pallidotomy related adverse event was previously reported as ongoing at Month 12 (Table 4a); moderate dysarthria. However, the subject reporting dysarthria (115011)
developed sepsis from a shoulder infection, died (see SAE narrative) and there was no follow-up resolution. There were no other ongoing procedure-related events as of Month 12 to follow.
2. Table 4b presents six adverse events in two subjects newly reported this period. All six events were mild or moderate in severity, none were reported as severe. All six events were reported as unrelated to the device or procedure by the investigators. The nausea and visual hallucinations resulted from a drug.
3. It should be noted that there have been no device/study related medical interventions under the PAS long term follow up.
4. In the Crossover there were three pallidotomy related events in two subjects ongoing at the Month 12 completion of the pivotal trial (Table 17a). The status of all ongoing adverse events were followed through to study exit/completion for each subject in the long-term study.
S018 (PD015): N/A
Effectiveness Results:
S014 (PD006)
1. The OFF Medication UPDRS Part III is shown in Figures 1a and 1b, and Table 6 and the UDysRS Objective Impairment is shown in Figures 2a and 2b, and Table 7 (Section 5.4.2 below). The UPDRS Part III and the UDysRS formed the basis of the Responder/Non-responder analysis at the Month 3 visit in the PMA. The Baseline, and Month 12 represent data already presented in the FDA approved PMA. This is included here for background reference, and trending comparison to the pivotal PMA study. Baseline scores were used to calculate change and percent change from baseline. Data listings for the MDS-UPDRS Part III – Motor Examination treated side extremities and the UDysRS Objective Impairment are presented in Appendix 1 and Appendix 2, respectively
2. The algorithms used to calculate the PD006 results in this report are the same as those for the PD006 as presented in the PMA (P380015/S14). The Crossover efficacy results through Month 3 were calculated using multiple imputation for missing values. The results presented in the following tables and figures were reported in the PMA and thus used multiple imputation. Post-PMA results are calculated using the observed data with no imputation. Since the sample size at Year 5 is n=2 the following tables and figures present Years 2-4; for Year 5 only basic sample statistics are presented in the tables.
3.We continue to follow subjects in the long term PD006 PAS. Although visit completion is ongoing in the main and crossover groups, the results overall are as expected and comparable to Month 12. Parkinson’s is a
progressive disease, and the condition of subjects can be expected to worsen over time. However, we expect only minor differences between analyses and completed visits presented in the annual and final reports.
S018 (PD015): N/A
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| Actual Number of Patients Enrolled |
S014 (PD006): 90
S018 (PD015): 6
Randomization in PD006 was 3:1, Exablate:Sham Control. For analysis there were initially 68 subjects in the PD006 Main Group and 22 subjects in the PD006 Crossover Group.
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| Actual Number of Sites Enrolled |
S014 (PD006): 16
S018 (PD015): 5
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| Patient Follow-up Rate |
S014 (PD006): Follow-up has been completed, and all subjects have exited the study. On page 13, the sponsor provided the follow-up date from Y2 to Y5 are 72%, 71 %, 70%, and 69%.
S018 (PD015): Six subjects have been enrolled, 3 of which have reached at least one follow-up timepoint. Results will begin to be analyzed for efficacy once a minimum of ten subjects have reached at least the 3-month follow-up timepoint.
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