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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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Post-Approval Study


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General
Study Status Progress Adequate
Application Number P140019 / PAS001
Date Current Protocol Accepted  
Study Name Post-Approval Study
General Study Protocol Parameters
Study Design Randomized Clinical Trial
Data Source New Data Collection
Comparison Group Concurrent Control
Analysis Type Analytical
Study Population Adult: >21
Detailed Study Protocol Parameters
Study Design Description The study is designed to assess the long-term (out to 6 years post-op) performance of i-FACTOR compared to local autograft by continued follow-up of available subjects from the approved IDE study. NO new subjects will be enrolled. Subjects, radiologists and neuro evaluators will remain blinded. Subjects will be informed of their treatment after the last evaluation.
Study Population Description study group: allograft ring filled with i-FACTOR and stabilized with metallic anterior plate system

control group: allograft ring filled with local autograft bone and stabilized with metallic anterior plate system
Sample Size 218 subjects from the IDE study (106 investigational and 112 control) provided informed consent for long-term follow-up. The sponsor estimates attrition of 10 subjects per year due to lost-to-follow-up or withdrawal with a follow-up rate of at least 70% for each assessment period. Table 6 of the submission provides detailed power estimates for each primary endpoint, however each endpoint will have a minimum of 80% at each timepoint.
Data Collection primary endpoints:

radiographic assessment of fusion

Neck Disability Index (NDI) for function

neuro evaluations

rate and type of AEs

lack of secondary surgical interventions at the treated spinal level

secondary endpoints:

neck and arm/shoulder pain using VAS

SF36v2 quality of life

modified Odom¿s criteria for surgical success
Follow-up Visits and Length of Follow-up Each subject will be followed for total of 6 years post-op.
Interim or Final Data Summary
Actual Number of Patients Enrolled A total of 220 subjects (106 i-FACTOR [identified a P-15 below] and 114 autograft control) participated in the study.
Actual Number of Sites Enrolled A total of 17 sites participated in the PAS.
Patient Follow-up Rate The follow-up rates at 72 months post-op were the following:



rate when counting only visits within windows and all primary endpoint data are available:

P-15 group 75.8%

control group 68.3%



rates when any visit data are available:

P-15 group 77.9%

control group 77.2%



While lower than the rates observed at 12 and 24 months post-op, these rates are reasonable for the extended follow-up time of the post-approval study.
Final Safety Findings The proportion of subjects with any AEs was 96.2% in the P-15 group and 97.4% in the control group. The difference in the proportion of subjects with any AEs between the groups was not statistically significant.



Secondary surgical interventions (SSI) at the treated level was better in the investigational group (16.7% P-15, 23.1% control). Need for SSI over time by study visit was comparable between study groups.



There were no deaths reported.



The PAS AE safety hypothesis was that complication rates at the follow-up visits should not differ between the P-15 group and the control group at 72 months post-op. The total number of unique events reported in the P-15 group was 847 compared with 892 events in the control group. Altogether, 102 subjects (96.2%) in the P-15 group had one or more AEs reported, compared to 111 subjects (97.4%) in the control group. The difference in the proportion of subjects with any AEs between the groups was not statistically significant.



AE and SAE rates were comparable between study groups, as were the categories and times of occurrence. AEs and SAEs by Body System, and Preferred Term showed no statistically significant difference between the 2 study groups, nor differences in time of presentation. In both study groups, study-related AEs were primarily reported on the C5/C6 and C5/C7 cervical level; there was no statistically significant difference between study groups in any category and on any cervical level



There are no significant differences in the AE rate between the two study arms besides the superficial infections which occurred at a significantly higher rate in the P-15 group (5 subjects, 4.7%) compared to the control group (0 subjects). Although this difference was statistically significant, the rate of superficial infection observed in the study was within the range of infection rates reported in literature for similar surgical procedures. Generally, these events resolved uneventfully and were short in duration. The number of occurrences did not raise any notable safety concerns.



The rates of device- and procedure-related AEs by System Organ Class per DMC adjudication were comparable between study groups. A total of 33 (31%) of P-15 subjects and 29 (25.4%) of control subjects experienced a device-related AE according to the DSMB, which is slightly lower than the number of study-related AEs reported by the Investigator. The rate of incidence in all categories was similar between groups, and any observed numerical differences and between-group differences did not reach statistical significance.

Final Effect Findings primary endpoints:

radiographic assessment of fusion

Neck Disability Index (NDI) for function

neurologic evaluations

rate and type of AEs

lack of SSI at the treated spinal level



Study success at 72 months was achieved if both the primary efficacy endpoints and the primary safety endpoint met the pre-defined success criteria for the composite endpoint:

• non-inferiority (NI, margin defined as 10%) of the P-15 group compared to the control group in fusion, and

• NI (defined as 11 points) of the P-15 group compared to the control group in NDI, and

• NI (defined as 15%) of the P-15 group compared to the control group in Neurological Success, and

• comparable or favorable AE outcomes in the P-15 group compared to the control group.



NI margins in the PAS were set to the same values as for the primary analysis of the IDE study. The outcome of the P-15 subjects was determined to be non-inferior to the control subjects at 72 months post-op.



secondary endpoints:

neck and arm/shoulder pain using VAS

SF36v2 quality of life

modified Odom’s criteria for surgical success



VAS Arm Pain: Mean arm pain was 7.34 in the P-15 group and 6.92 in the control group at baseline and dropped to 1.51 in the P-15 group and 2.45 in the control group by 72 months post-op. Difference in the pain score between the study groups reached statistical significance at 3, 6, and 72 months.



VAS Neck Pain: At most time points the mean pain score was lower for the P-15 group than for the control group.



Quality of Life (SF36v2 Physical and Mental Component Summaries): Elevations in both of these components were maintained throughout the study in both treatment groups. In addition, Bodily Pain, Mental Health, Vitality, General Health, Physical Functioning, Role limitation emotional, Role Limitation physical, and Social Functioning scale changes were consistently elevated from baseline and maintained throughout the PAS in both groups.



Surgical Success (Modified Odom’s Criteria): There was comparable improvement in both groups at all provided visits. Any differences between groups were not statistically significant.

Study Strengths & Weaknesses The study described the longer-term clinical, radiographic and safety performance of the i-FACTOR Peptide Enhanced Bone Graft for instrumented cervical spine fusions to treat single level degenerative disc disease compared to the same treatment using allograft bone rings filled with local autograft bone. The population consisted of continued follow-up of the original IDE study subjects. No new subjects were enrolled. Subjects, radiologists and neuro evaluators remained blinded. Subjects were informed of their treatment after the last evaluation.



While the follow-up rates at the longer timepoints were lower than those that would be excepted for ongoing follow-up during the course of an IDE and for filing a PMA, they are reasonable rates for a post-approval study collecting data out to 6 years post-op.

Recommendations for Labeling Changes There are no new safety or efficacy findings that alter the conclusions that led to PMA approval, or would require addition to labeling. The sponsor has been instructed to submit a modified package insert containing the updated timecourse distributions of AEs and clinical and radiographic outcome out to 72 months post-op.


Post-Approval Study Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
six month report 05/03/2016 04/29/2016 On Time
one year report 11/02/2016 11/02/2016 On Time
18 month report 05/03/2017 05/02/2017 On Time
two year report 11/02/2017 11/02/2017 On Time
three year report 11/02/2018 11/02/2018 On Time
final report 02/28/2020 03/02/2020 Overdue/Received


Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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