Infuse Bone Graft

{0} # SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) ## I. GENERAL INFORMATION | Device Generic Name: | Filler, recombinant human bone morphogenetic protein, collagen scaffold, osteoinduction | | --- | --- | | Device Trade Name: | Infuse™ Bone Graft | | Device Product Code: | NEK | | Applicant’s Name and Address: | Medtronic Sofamor Danek 1800 Pyramid Place Memphis, TN 38132 | | Date(s) of Panel Recommendation: | None | | Premarket Approval Application (PMA) Number: | P000058/S096 | | Date of FDA Notice of Approval: | February 13, 2026 | **Breakthrough Device:** Granted breakthrough device status on April 6, 2024, because the use of the combination product at one or two adjacent levels in transforaminal lumbar interbody fusion (TLIF) procedures represents a novel application of an existing technology that provides for more effective treatment of irreversibly debilitating human disease. The original PMA, P000058, was approved on July 2, 2002, and is indicated for “spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one level from L4-S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient history, function deficit and/or neurological deficit and radiographic studies. These DDD patients may also have up to Grade I spondylolisthesis at the involved level. InFUSE™ Bone Graft/LT-CAGE™ devices are to be implanted via an anterior open or an anterior laparoscopic approach. Patients receiving the InFUSE™ Bone Graft/ LT-CAGE™ Lumbar Tapered Fusion Device should have had at least six months of nonoperative treatment prior to treatment with the InFUSE™ Bone Graft/LT-CAGE™ device.” The SSED to support the indication is available on the CDRH website and is incorporated by reference here. The current supplement was submitted to expand the indication for Infuse™ Bone Graft. ---PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 1 of 59 {1} ## **II. INDICATIONS FOR USE** Infuse™ Bone Graft with an FDA cleared intervertebral body fusion device and metallic screw-and-rod system is indicated for use in a transforaminal lumbar interbody fusion (TLIF) surgical approach at one or two adjacent levels from L2-S1 in the treatment of symptomatic degenerative disc disease (DDD) confirmed by patient history and radiographic studies and having at least six months of nonoperative treatment attempted prior to treatment with Infuse™ Bone Graft. ## **III. CONTRAINDICATIONS** Infuse™ Bone Graft is contraindicated for patients with: - A known hypersensitivity to recombinant human Bone Morphogenetic Protein-2, bovine Type I collagen, or to other components of the formulation or with an allergy to titanium, titanium alloy, or polyetheretherketone. - Known history of resected or extant tumor in the vicinity, or in patients with any active malignancy or undergoing treatment for a malignancy. - Patients who are skeletally immature or <22 years of age. - Current or future pregnancy. The potential effects of rhBMP-2 on the human fetus have not been evaluated. - Patients with an active infection at the operative site. ## **IV. WARNINGS AND PRECAUTIONS** The warnings and precautions can be found in the Infuse™ Bone Graft labeling. ## **V. DEVICE DESCRIPTION** Infuse™ Bone Graft consists of two components – a recombinant human bone morphogenetic protein solution and a collagen sponge which acts as a carrier for the bone morphogenetic protein and as a scaffold for new bone formation. These components must be used as a system. The bone morphogenetic protein solution component must not be used without the carrier/scaffold component or with a carrier/scaffold component different from the one described in this document. Infuse™ Bone Graft consists of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2, known as dibotermin alfa) placed on an absorbable collagen sponge (ACS). Infuse™ Bone Graft induces new bone tissue at the site of implantation. Based on data PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 2 of 59 {2} from non-clinical studies, the bone formation process develops from the outside of the implant towards the center until the entire Infuse™ Bone Graft is replaced by trabecular bone. rhBMP-2, an osteoinductive growth factor, is the active agent in Infuse™ Bone Graft. It consists of a disulfide-linked dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit is glycosylated at one site with high-mannose-type glycans. rhBMP-2 is produced by a genetically engineered Chinese hamster ovary cell line. rhBMP-2 and excipients are lyophilized. Upon reconstitution, each milliliter of rhBMP-2 solution contains: 1.5mg of rhBMP-2; 5.0mg sucrose, NF; 25mg glycine, USP; 3.7mg L-glutamic acid, FCC; 0.1mg sodium chloride, USP; 0.1mg polysorbate 80, NF; and 1.0mL of sterile water. The reconstituted rhBMP-2 solution has a pH of 4.5; is clear, colorless to slightly yellow; and is essentially free from plainly visible particulate matter. The concentration of rhBMP-2 is 1.5mg/ml. The absorbable collagen sponge (ACS) is a soft, white, pliable, absorbent implantable matrix for rhBMP-2. ACS is made from bovine Type I collagen obtained from the deep flexor (Achilles) tendon. The ACS acts as a carrier for the rhBMP-2 and acts as a scaffold for new bone formation.  Figure 1. Left: Infuse™ Bone Graft (X-small kit); Right: Image of wetted and rolled Infuse™ Bone Graft sponge to facilitate delivery. Each kit contains all the components necessary to prepare Infuse™ Bone Graft: the rhBMP-2, which must be reconstituted; sterile water; absorbable collagen sponge(s); syringes with needles; and instructions for preparation. The number of each item may vary depending on the size of the kit (see Table 1 below). PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 3 of 59 {3} Table 1: Infuse Bone Graft kit sizes for one-level and two-level TLIF procedures | | Infuse™ Bone Graft Kit Description | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | | | XX small | X small | Small | Medium | Large | Large II | | Volume (rhBMP-2 dose) | | 0.7 cc (1.05 mg) | 1.4 cc (2.1 mg) | 2.8 cc (4.2 mg) | 4.2 cc (8.4 mg) | 8 cc (12 mg) | 8 cc (12 mg) | | Total number of required kits to achieve dose | | | | | | | | | ONE-LEVEL TLIF Procedure | 2.1 mg rhBMP-2 per level | 2 kits | 1 kit | 1/2 kit | 1/4 kit | 1/6 kit | 1/6 kit | | | 4.2 mg rhBMP-2 per level | 4 kits | 2 kits | 1 kit | 1/2 kit | 1/3 kit | 1/3 kit | | TWO-LEVEL TLIF Procedure | 2.1 mg rhBMP-2 per level | 4 kits | 2 kits | 1 kit | 1/2 kit | 1/3 kit | 1/3 kit | | | 4.2 mg rhBMP-2 per level | 8 kits | 4 kits | 2 kits | 1 kit | 2/3 kit | 2/3 kit | The rhBMP-2 is provided as a lyophilized powder in vials delivering 1.05 mg to 12 mg of protein. After appropriate reconstitution, the concentration of rhBMP-2 is 1.5mg/mL. The solution is then applied to the provided ACS. Infuse™ Bone Graft is prepared at the time of surgery and allowed a prescribed amount of time (no less than 15 minutes and no more than 2 hours) before placement at the site of implantation. The Instructions for Preparation contains complete details on preparation of Infuse™ Bone Graft. ### VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several non-surgical and surgical alternatives for the treatment of symptomatic lumbar degenerative disc disease (DDD). Non-surgical alternatives may include physical therapy, activity modification, and pharmacologic pain management. When non-operative managements cease to be effective, there are several surgical alternatives, which include, but are not limited to, surgical decompression alone and surgical decompression with spinal instrumentation and fusion. Each option has its own advantages and disadvantages. Patients should discuss risks, benefits and alternatives to all treatment options with their physicians. ### VII. MARKETING HISTORY Infuse™ Bone Graft has been marketed in dozens of countries under the names of Infuse™ Bone Graft or InductOs®. The product has not been withdrawn from any of these countries for any reason related to its safety or effectiveness. ### VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of potential adverse events (e.g., complications) associated with the use of Infuse™ Bone Graft when used with a FDA cleared intervertebral body fusion device and PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 4 of 59 {4} metallic screw-and-rod system The adverse effects are sub-divided into three categories: (1) those commonly associated with any surgical procedure; (2) those associated with lumbar spinal surgery procedures using a transforaminal lumbar interbody fusion (TLIF) approach; and (3) those associated with the use of bone graft, include those pertaining to Infuse Bone Graft™. In addition to the risks listed below, there is also the risk that the procedure may not be effective and may not relieve or may cause worsening of pre-operative symptoms. Additional surgery may be required to correct some of the potential adverse effects. Potential adverse effects associated with any surgical procedure include: - Anesthesia complications, including allergic reaction, anaphylaxis, or other reactions to anesthesia - Reaction to transfused blood - Anemia - Blood loss/hemorrhage - Heart or vascular complications, including: - Excessive bleeding or injury to blood vessels - Edema - Hematoma or seroma - Hypotension or hypertension - Ischemia - Cardiac event - Myocardial infarction - Embolism, including pulmonary embolism - Thrombosis - Thromboembolism - Thrombophlebitis - Phlebitis - Stroke - Hemorrhage or vascular damage resulting in catastrophic or potentially fatal bleeding - Septicemia - Cerebral vascular accident (stroke) - Pulmonary complications, including atelectasis, pneumothorax, pneumonia, pulmonary edema, and respiratory distress - Blindness secondary to pressure on the eye during surgery - False aneurysm - Headache - Infection (wound, local, and/or systemic) abscess, or cellulitis - Soft tissue damage or fluid collections, including edema, hematoma, or seroma, which may require drainage, aspiration, debridement, or other intervention - Surgical wound dehiscence, necrosis, or scarring of tissue around the wound PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 5 of 59 {5} - Post-surgical pain, bruising, tenderness or discomfort at the surgical site or incision and/or skin or muscle sensitivity over the incision which may result in skin breakdown, pain, and/or irritation - Impairment of the gastrointestinal system including ileus or bowel obstruction, nausea, or vomiting - Impairment of the genitourinary system including incontinence, bladder dysfunction, urinary tract infection, or reproductive system complications - Neurological complications including nerve damage, paralysis, seizures or convulsions, changes to mental status, or reflex sympathetic dystrophy - Psychological illness - Injury to muscles, or organs - Insomnia - Narcotic addiction - Numbness - Complications of pregnancy including miscarriage or congenital defects - Inability to resume activities of daily living - Death Potential adverse effects associated with an instrumented TLIF surgery (one- and two-levels) with any type of bone graft include: - Risks to neurological structures - Dural tear dural leak and/or dural injury with or without CSF leakage - Arachnoiditis - Compressive neuropathy - Neurologic deterioration - injury to nerves or nerve roots associated with the spinal cord (resulting in pain, weakness, paralysis (partial or complete), paresthesia, altered reflexes, numbness, tingling, or other changes in sensation) - Coordination abnormalities - Gait disturbance - Headache - Otitis media - Tremors - Cerebrospinal fluid leakage - Cerebrospinal fistula - Reflex Sympathetic Dystrophy (RSD) / Chronic Regional Pain Syndrome (CRPS) - Cauda equina syndrome - Damage to nerves, blood vessels, and nearby tissues - Impaired muscle or nerve function - Epidural bleeding, hematoma, or fibrosis - Bone necrosis PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 6 of 59 {6} - Degenerative changes in adjacent segment - Surgery at incorrect level - Osteolysis - Loss of bowel or bladder function - Incontinence (loss of bowel or bladder control) - Fracture of the vertebrae, spinous process, or other damage to bony structures during or after surgery - Postoperative muscle and tissue pain - Development of disc degeneration at adjacent levels - Inflammatory conditions - Loss of disc height - Disc herniation - Undesirable change in lordosis - Scarring or soft tissue damage - Spinal instability - Spondylolisthesis, acquired (vertebral slippage) - Retrolisthesis - Spinal stenosis (narrowing of the spinal canal) - Spondylosis - Facet joint deterioration - Infection of the bone, or surrounding soft tissue - Musculoskeletal spasms (back or leg) - Perineural fibrosis - Surgery may not reduce the preoperative pain - Pain and discomfort associated with the presence of implants - Pain and discomfort associated with the surgical procedure (e.g., cutting of muscles, ligaments, and tissue) and healing - The spine may undergo adverse changes or deterioration including loss of proper spinal curvature, correction, height, and/or reduction, or malalignment, and another surgery may be required - Adverse bone/implant interface reaction - Extrusion or migration of the bone graft, resulting in pain, neural impingement, physical impairment, or loss of function, any of which may require revision surgery - Abnormal bone formation in an unintended location - Excessive or incomplete bone formation Potential adverse effects associated with the use of Infuse™ Bone Graft include: - Allergic/immune reaction to the components of Infuse™ Bone Graft PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 7 of 59 {7} For the specific adverse events that occurred in the clinical study, please see **Section X** below. ## IX. SUMMARY OF NON-CLINICAL STUDIES Technological characteristics of Infuse™ Bone Graft have not changed since approval rendered in P000058. Data presented in P000058 were adequate to address necessary characterization of the properties and performance of the Infuse™ Bone Graft. A summary of the preclinical studies conducted in support of Infuse™ Bone Graft is available in the SSED for P000058 on the CDRH website. ## X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of Infuse™ Bone Graft for treatment of symptomatic degenerative disc disease (DDD) for use in TLIF procedures with intervertebral body fusion device and metallic screw-and-rod systems in one or two levels from L2-S1 for patients with at least six months of nonoperative treatment. The clinical study was conducted in the US and China under IDE G180160. Data from this clinical study were reviewed for the PMA approval decision. A summary of the clinical study is presented below. ### A. Study Design Subjects (patients) were treated between December 19, 2019, and April 15, 2025. The database for this Panel Track PMA Supplement reflected data collected through April 15, 2025, and included 480 patients. There were 53 investigational sites. The study is ongoing, and continuation is planned until all enrolled, randomized and implanted patients achieve 24 months follow-up after operative intervention. The study was a prospective, randomized, controlled, single (subject)-blinded multi-center clinical study. The objective of the study was to evaluate whether Infuse™ Bone Graft (used in two different volumes) at 1 or 2 lumbar spinal levels was noninferior in overall success and superior in fusion at 24 months to local autologous bone when applied in instrumented TLIF with use of an interbody fusion device and supplemental fixation in subjects with symptomatic lumbar degenerative disc disease having undergone at least 6 months of conservative treatment. Subjects were randomized 1:1:1 into 3 groups (2 investigational and 1 control) consisting of Infuse™ Bone Graft 2.1 mg/level; Infuse™ Bone Graft 4.2 mg/level; or local bone autograft. All subjects received an FDA-cleared intervertebral body fusion device and metallic screw-and-rod system and local autograft with optional mineralized cancellous allograft implanted in the interbody space. Two level subjects received the same volume of Infuse™ Bone Graft at both levels. One TLIF interbody fusion device was used per level. When used, Infuse™ Bone Graft was placed in the anterior and contralateral portion of the disc space relative to the interbody fusion device surrounded with autograft and optionally ---PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 8 of 59 {8} supplemented with allograft. All bone grafting was in the interbody space alone, without grafting in the posterolateral space. A Bayesian adaptive design was used, which allowed for the early termination of enrollment for either early success or early futility. The early success criterion based on the posterior probabilities of success on Overall Success (>0.96) and Radiographic Fusion Success (>0.975) was met at the first interim analysis, so the study stopped enrolling. Submitted data includes all outcome data, in particular the 12-month and 24-month Overall Success and Radiographic Fusion Success outcomes. All subjects will be followed to the 24-month visit for the final analysis. The primary outcome measure for the noninferiority hypothesis was Overall Success, a subject-level composite endpoint consisting of both effectiveness and safety measurements. To achieve Overall Success at 24 months, a subject must have met success criteria for each of the five components at 24 months: Radiographic Fusion Success, Oswestry Disability Index (pain/disability status), Neurological Status, no serious adverse events (SAEs) related to the TLIF grafting material or interbody device, and no secondary surgeries classified as failure. Radiographic Fusion Success, a co-primary study endpoint and the primary outcome measure for the superiority hypothesis, required CT-evidence of bridging bone and no evidence of motion as defined by less than 2 mm translational motion and less than 3° in angular motion at each treated level on flexion/extension radiographs. Secondary endpoints included time to fusion; ODI, leg pain, back pain, and neurological success; secondary surgeries up to 24 months classified as failure; and interbody device- or grafting material-related SAEs up to 24 months. A core laboratory performed image analysis (Medical Metrics, Inc., Houston TX). An independent Data Monitoring Committee (DMC) oversaw the progress and accumulation of the data. A Clinical Events Committee (CEC) reviewed data for final classification for adjudication parameters. The CEC conducted a medical review and classification adjudication for relatedness and severity of all adverse events (AEs) and additional surgical procedures. 1) Key Clinical Inclusion and Exclusion Criteria Enrollment in the study was limited to patients who met the following inclusion criteria: - Had radiographic evidence of degenerative disease of the lumbosacral spine in one or two adjacent levels (L2 to S1) that resulted in radiculopathy secondary to nerve root compression. - Had radiographic evidence of degenerative disease of the lumbosacral spine, including at least one of the following: PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 9 of 59 {9} a. Instability up to and including Grade 2 spondylolisthesis/retrolisthesis b. Stenosis, or narrowing, of the lumbar spinal canal and/or intervertebral foramen requiring significant decompression leading to segmental instability, or c. Recurrent disc herniation. - Had preoperative Oswestry Disability Index (ODI) score ≥ 35. - Was at least 18 years of age and skeletally mature at the time of surgery. - Had not responded to non-operative treatment for a period of six months. - Planned treatment with TLIF procedure with intervertebral fusion device and posterior supplemental fixation at 1- or 2-levels. Patients were not permitted to enroll in the study if they met any of the following exclusion criteria: - Prior surgical procedure at the involved or adjacent spinal levels (e.g., fusion, arthroplasty, and/or other non-fusion procedures). Prior discectomy and/or laminectomy at the target or adjacent levels was allowed. - Planned use of an internal or external bone growth stimulator. - Lumbar scoliosis > 30 degrees. - Morbidly obese, as defined by a body mass index (BMI) > 40. - Presence of active malignancy or prior history of malignancy (non-invasive basal cell carcinoma of the skin and non-invasive squamous cell carcinoma localized only to the skin was allowed). - Overt or active bacterial infection, either local to surgical space or systemic. - Autoimmune disease, which in the investigator's opinion, is known to affect bone metabolism or the spine. - Any endocrine or metabolic disorder, which in the investigator's opinion, is known to affect osteogenesis. - Known exposure to any recombinant proteins used for bone formation. - Known hypersensitivity or allergy to any components of the study treatments including but not limited to bone morphogenetic proteins (BMPs); injectable collagen; protein pharmaceuticals bovine collagen products; and/or instrumentation materials (e.g., titanium, titanium alloy, cobalt chrome, cobalt chrome alloy, or polyetheretherketone [PEEK]). - Pregnant or nursing. Females of child-bearing potential had to agree not to become pregnant for 24 months following surgery. PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 10 of 59 {10} # 2) Follow-up Schedule All subjects were scheduled to return for follow-up examinations at 6 weeks and 3, 6, 12, and 24 months after surgery, then annually until the last subject enrolled in the study has reached 24 months after surgery. All subjects followed the same schedule of events, shown in **Table 2**. **Table 2: Schedule of Events** | Procedure | Pre-Perioperative | | Post-operative | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Preop: Baseline^{4} | Surgery/ Hospital Discharge | 6 wks 42 days ±14 days | 3 mo 90 days ±30 days | 6 mo 180 days ±30 days | 12 mo 365 days ±60 days | 24 mo 730 days ±60 days | Annual Visits^{5} (36,48,60 mo) 1095, 1460, 1825 days ±120 days | Unscheduled Visit | | Inclusion/ Exclusion criteria | X | | | | | | | | | | Informed Consent | X | | | | | | | | | | Demographics | X | | | | | | | | | | Screening Log | X | | | | | | | | | | Medical History | X | | | | | | | | | | Surgical History (Lumbar only) | X | | | | | | | | | | Randomization | X | | | | | | | | | | Preoperative Pregnancy Test^{1} | X | | | | | | | | | | DEXA^{2} | X | | | | | | | | | | Device Identification | | X | | | | | | | | | Device Tracking | | X | | | | | | | | | Surgery Data | | X | | | | | | | | | Hospital Discharge | | X | | | | | | | | | ODI – Oswestry Disability Index^{3} | X | | X | X | X | X | X | X | | | Back & Leg Pain Questionnaire | X | | X | X | X | X | X | X | | | EQ-5D-5L Questionnaire | X | | X | X | X | X | X | X | | | Subject Satisfaction | | | X | X | X | X | X | X | | | Neurological Status | X | | X | X | X | X | X | | | | Medications | X | X | X | X | X | X | X | X | X | | Adverse Event (if any) | | X | X | X | X | X | X | X | X | | Additional Surgery (if any) | | X | X | X | X | X | X | X | X | | Device Deficiency | | X | X | X | X | X | X | X | X | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 11 of 59 {11} | Procedure | Pre-Perioperative | | Post-operative | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Preop: Baseline^{4} | Surgery/ Hospital Discharge | 6 wks 42 days ±14 days | 3 mo 90 days ±30 days | 6 mo 180 days ±30 days | 12 mo 365 days ±60 days | 24 mo 730 days ±60 days | Annual Visits^{5} (36,48,60 mo) 1095, 1460, 1825 days ±120 days | Unscheduled Visit | | (if any) | | | | | | | | | | | Protocol Deviation (if any) | X | X | X | X | X | X | X | X | X | | **Radiographic Procedures** | | | | | | | | | | | X-Ray Anterior/Posterior^{6} | X | X | X | X | X | X | X | | | | X-Ray A/P Ferguson (only if L5-S1) | X | X | X | X | X | X | X | | | | X-Ray Lateral | X | X | X | X | X | X | X | | | | X-Ray Flexion/Extension | X | | | X | X | X | X | | | | CT (high resolution axial, sagittal and coronal reformatting)^{7} | CT or MRI^{8} | | | | | X | X | | | | 1. A pregnancy test will be administered to all female subjects of child-bearing potential within 3 days prior to surgery. 2. Not all subjects will require a DEXA scan. A DEXA Scan will only need to be obtained if the subject had a prevalent fragility fracture but has not had a T-score assessed within 12 months prior to enrollment. 3. The ODI is a subject reported outcome which is also considered part of the primary endpoint; please double check the questionnaire is completed accurately prior to the end of the subject visit. 4. The pre-operative assessments should be obtained within 3 months prior to the date of surgery. Pre-existing radiographs within 3 months prior to enrollment are acceptable and should not be repeated for study purposes. 5. Visits will be performed annually until the end of the study (i.e., until the final subject enrolled completes his/her 24-month visit), or the subject has completed their 5-year visit, whichever comes first. 6. For levels between L2 and L5 (or L6, if applicable). 7. CT not required after the 24-month postoperative evaluation. 8. A Baseline CT or MRI will only need to be obtained if the subject does not have a CT or MRI within 12 months of enrollment for the investigator's inclusion criteria assessment. | | | | | | | | | | Adverse events and complications were recorded at all visits. The key timepoints are shown below in the tables summarizing safety and effectiveness. ### 3) Clinical Endpoints The primary endpoints were Overall Success and Radiographic Fusion Success, assessed during the 24-month visit: - Overall Success (subject must have met success criteria for each of the following five components): - Radiographic Fusion Success - ODI success (at least a 15-point improvement from baseline) PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 12 of 59 {12} ○ Neurological success (improvement or maintenance from baseline in all following four domains: motor and sensory function, reflexes and straight leg raise) ○ No Serious Adverse Events (SAEs) related to TLIF grafting material or intervertebral body fusion device ○ No additional surgeries at index level(s) related to TLIF grafting material or intervertebral body fusion device • Radiographic Fusion Success ○ Bridging bone success based on CT assessment ○ No evidence of motion as defined by less than 2mm translational motion and less than 3° in angular motion at each treated level (flexion/extension radiographs). In addition, adverse events (AEs) were evaluated during and after surgery and tabulated as to the nature and frequency of AEs, additional surgical procedures, and a subject's neurological status, if applicable. An independent Data Monitoring Committee (DMC) monitored the safety of the investigational treatments, as well as the effectiveness performance. The secondary objectives included: • assessing whether statistical difference exists between the investigational groups and the control group for the secondary endpoints listed below; and • demonstrating superiority in Overall Success at 24 months postoperatively for the investigational group as compared to the control group if noninferiority is achieved. For the secondary objectives, the multiplicity due to multiple endpoints was controlled using the gatekeeping method. The gatekeeping was performed separately for each dose that met the success criteria on the primary endpoints. As long as the noninferiority criteria were met for an endpoint, the sequential testing procedure proceeded to test noninferiority of the next endpoint in the hierarchy. The hierarchy is listed below for the secondary endpoints: (1) Time to fusion (2) Secondary surgeries up to 24 months that are classified as failure (3) ODI Success at 24 months (4) Leg pain success at 24 months (5) SAEs up to 24 months that are "related" to TLIF grafting material or interbody device (6) Back pain success at 24 months (7) Neurological success at 24 months Tests for noninferiority were performed at a 1-sided 5% level while tests for superiority were performed at a 1-sided 2.5% level. PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 13 of 59 {13} ## **B. Accountability of PMA Cohort** At the time of PMA application review, 684 patients were enrolled, and consented in the clinical study, of which 480 patients were randomized and treated (379 one-level patients, 101 two-level patients). Of the randomized and treated population, the 379 one-level patients were comprised of 149 patients from outside the US (OUS) and 230 patients were from US sites. The two-level patients were comprised of 31 patients OUS and 70 patients from US sites. The follow-up rate of the randomized and treated populations pooled by levels from all sites at the time of the interim analysis for PMA application review was 84.4% one-level patients and 78.2% two-level patients achieving 12 months of follow-up after operative intervention, and 62.5% one-level patients and 61.4% two-level patients achieving 24 months of follow-up after operative intervention. The follow-up rate of the as-treated populations pooled by levels from all sites at the time of this interim analysis for PMA application review was 83.9% one-level patients and 80.2% two-level patients achieving 12 months of follow-up after operative intervention, and 62.2% one-level patients and 62.5% two-level patients achieving 24 months of follow-up after operative intervention. No further enrollment is occurring, but the study will continue until all enrolled, consented, randomized and treated subjects have been followed for 24 months after operative intervention. The analysis populations are described below. - Primary Dataset (As Randomized and Treated; ART): used as the primary dataset for the main statistical analyses. The ART dataset included subjects who were enrolled, randomized and received treatment. Subjects were analyzed according to the treatment to which they were randomized. - As Treated Dataset (AT): used for safety evaluation. This dataset included all subjects who were enrolled, randomized, and received treatment. Subjects were analyzed according to the treatment received. - Per-Protocol (PP): This dataset included subjects who were enrolled, randomized, received the randomized treatments, and did not have any major protocol deviation. Two PP datasets were derived; one for deviations assessed per the protocol version in place at the time of the event and one that assessed the event according to the criteria in the final version of the protocol. The PP dataset considered for the interim evaluation at the time of PMA application PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 14 of 59 {14} was the PP dataset that considered protocol deviations according to the criteria in the final version of the protocol. Figure 1 conveys the enrollment, allocation, and analysis of the subjects. Figure 1: Process of enrollment, allocation, and analysis of subjects  PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 15 of 59 {15} Table 3: Summary of accountability by treatment group based on all subjects | | One-level Subjects (N = 129, 128, 122 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 129 | 128 | 122 | 129 | 128 | 122 | 129 | 128 | 122 | 129 | 128 | 122 | 129 | 128 | 122 | 129 | 128 | 122 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 3 | 3 | 5 | 6 | 4 | 6 | 13 | 10 | 8 | 21 | 21 | 17 | 51 | 47 | 44 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 2 | 1 | 2 | 3 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 0 | 4 | 2 | 1 | 5 | 3 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 4 | 1 | 3 | 0 | 3 | 5 | 5 | 4 | 3 | 7 | 2 | | Expected ^{c} | 129 | 128 | 122 | 126 | 124 | 117 | 121 | 120 | 114 | 112 | 115 | 107 | 102 | 97 | 97 | 72 | 66 | 70 | | Evaluated of Expected ^{d} | 129 | 128 | 122 | 125 | 121 | 115 | 119 | 113 | 110 | 110 | 113 | 105 | 99 | 97 | 95 | 72 | 64 | 70 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 99.2 | 97.6 | 98.3 | 98.3 | 94.2 | 96.5 | 98.2 | 98.3 | 98.1 | 97.1 | 100.0 | 97.9 | 100.0 | 97.0 | 100.0 | | | Two-level Subjects (N = 34, 32, 35 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 34 | 32 | 35 | 34 | 32 | 35 | 34 | 32 | 35 | 34 | 32 | 35 | 34 | 32 | 35 | 34 | 32 | 35 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 2 | 2 | 4 | 6 | 5 | 7 | 8 | 7 | 11 | 13 | 15 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 2 | | Expected ^{c} | 34 | 32 | 35 | 34 | 31 | 34 | 32 | 30 | 32 | 30 | 26 | 30 | 27 | 24 | 25 | 20 | 19 | 17 | | Evaluated of Expected ^{d} | 34 | 32 | 35 | 34 | 31 | 34 | 32 | 30 | 31 | 30 | 26 | 29 | 26 | 24 | 25 | 19 | 19 | 16 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 96.9 | 100.0 | 100.0 | 96.7 | 96.3 | 100.0 | 100.0 | 95.0 | 100.0 | 94.1 | | ^{a} Patients whose lower bound of the visit window is after the cut off date (4/15/2025). ^{b} Patients who has not completed follow-up visit and the upper bound of visit window is after the cut off date (4/15/2025). ^{c} Expected = (Enrolled and Included in the Analysis) - (Not due for the visit) - (Cumulative Deaths + Cumulative LTF + Cumulative Withdrawal + Cumulative Other) - (Not Yet Overdue). ^{d} Patients who have any observed clinical data except AE in a given study period. | | | | | | | | | | | | | | | | | | | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 16 of 59 {16} **Table 4: Summary of accountability by treatment group based on subjects from OUS** | | One-level Subjects (N = 49, 51, 49 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 8 | 6 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | | Expected ^{c} | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 49 | 51 | 49 | 40 | 40 | 42 | | Evaluated of Expected ^{d} | 49 | 51 | 49 | 49 | 49 | 48 | 49 | 50 | 48 | 47 | 51 | 48 | 49 | 51 | 49 | 40 | 39 | 42 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 100.0 | 96.1 | 98.0 | 100.0 | 98.0 | 98.0 | 95.9 | 100.0 | 98.0 | 100.0 | 100.0 | 100.0 | 100.0 | 97.5 | 100.0 | | | Two-level Subjects (N = 14, 7, 10 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | | Expected ^{c} | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 10 | 6 | 9 | | Evaluated of Expected ^{d} | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 14 | 7 | 10 | 13 | 7 | 10 | 10 | 6 | 8 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 92.9 | 100.0 | 100.0 | 100.0 | 100.0 | 88.9 | $^{a}$ Patients whose lower bound of the visit window is after the cut off date (4/15/2025). $^{b}$ Patients who has not completed follow-up visit and the upper bound of visit window is after the cut off date (4/15/2025). $^{c}$ Expected = (Enrolled and Included in the Analysis) - (Not due for the visit) - (Cumulative Deaths + Cumulative LTF + Cumulative Withdrawal + Cumulative Other) - (Not Yet Overdue). $^{d}$ Patients who have any observed clinical data except AE in a given study period. PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 17 of 59 {17} **Table 5: Summary of accountability by treatment group based on subjects from US** | | One-level Subjects (N = 80, 77, 73 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 80 | 77 | 73 | 80 | 77 | 73 | 80 | 77 | 73 | 80 | 77 | 73 | 80 | 77 | 73 | 80 | 77 | 73 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 3 | 3 | 5 | 6 | 4 | 6 | 13 | 10 | 8 | 21 | 21 | 17 | 43 | 39 | 38 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 2 | 1 | 2 | 3 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 0 | 4 | 2 | 1 | 5 | 3 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 4 | 1 | 3 | 0 | 3 | 5 | 5 | 4 | 2 | 5 | 1 | | Expected ^{c} | 80 | 77 | 73 | 77 | 73 | 68 | 72 | 69 | 65 | 63 | 64 | 58 | 53 | 46 | 48 | 32 | 26 | 28 | | Evaluated of Expected ^{d} | 80 | 77 | 73 | 76 | 72 | 67 | 70 | 63 | 62 | 63 | 62 | 57 | 50 | 46 | 46 | 32 | 25 | 28 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 98.7 | 98.6 | 98.5 | 97.2 | 91.3 | 95.4 | 100.0 | 96.9 | 98.3 | 94.3 | 100.0 | 95.8 | 100.0 | 96.2 | 100.0 | | | Two-level Subjects (N = 20, 25, 25 for 2.1 mg, 4.2 mg and Ctrl) | | | | | | | | | | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | Surgery | | | 6 Weeks | | | 3 Months | | | 6 Months | | | 12 Months | | | 24 Months | | | | | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | 2.1 mg | 4.2 mg | Ctrl | | Number of Patients | 20 | 25 | 25 | 20 | 25 | 25 | 20 | 25 | 25 | 20 | 25 | 25 | 20 | 25 | 25 | 20 | 25 | 25 | | Patients Not Due for the Visit ^{a} | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 2 | 2 | 4 | 6 | 5 | 7 | 8 | 7 | 9 | 12 | 14 | | Cumulative Withdrawals | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | | Cumulative Deaths | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Cumulative Other Reasons (including Sponsor Request) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | | Patient Not Yet Overdue ^{b} | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 2 | | Expected ^{c} | 20 | 25 | 25 | 20 | 24 | 24 | 18 | 23 | 22 | 16 | 19 | 20 | 13 | 17 | 15 | 10 | 13 | 8 | | Evaluated of Expected ^{d} | 20 | 25 | 25 | 20 | 24 | 24 | 18 | 23 | 21 | 16 | 19 | 19 | 13 | 17 | 15 | 9 | 13 | 8 | | Percent of Follow-up (%) | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 100.0 | 95.5 | 100.0 | 100.0 | 95.0 | 100.0 | 100.0 | 100.0 | 90.0 | 100.0 | 100.0 | $^{a}$ Patients whose lower bound of the visit window is after the cut off date (4/15/2025). $^{b}$ Patients who has not completed follow-up visit and the upper bound of visit window is after the cut off date (4/15/2025). $^{c}$ Expected = (Enrolled and Included in the Analysis) - (Not due for the visit) - (Cumulative Deaths + Cumulative LTF + Cumulative Withdrawal + Cumulative Other) - (Not Yet Overdue). $^{d}$ Patients who have any observed clinical data except AE in a given study period. PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 18 of 59 {18} ### C. Study Population Demographics and Baseline Parameters Key demographic information is summarized in the following table for one-level and two-level subjects (Table 6). There were no statistically significant differences across groups. **Table 6: Summary of demographic information by treatment group based on all subjects** | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | **Age at Randomization (years)** | | | | | | | | Number of Subjects with Data Available (n) | 129 | 128 | 122 | 34 | 32 | 35 | | Mean (SD) | 60.9 (10.4) | 61.8 (11.2) | 59.5 (9.5) | 63.1 (8.0) | 61.4 (11.3) | 63.2 (8.7) | | Median | 60.8 | 62.8 | 59.9 | 64.0 | 64.0 | 64.4 | | Min-Max | 32.2-80.8 | 30.6-82.4 | 30.6-78.3 | 47.8-74.7 | 26.9-78.3 | 39.6-78.1 | | **BMI (kg/m^{2})** | | | | | | | | Number of Subjects with Data Available (n) | 129 | 128 | 122 | 34 | 32 | 35 | | Mean (SD) | 28.1 (5.2) | 28.7 (4.9) | 28.2 (4.8) | 28.1 (3.9) | 29.7 (4.9) | 30.8 (5.1) | | Median | 27.0 | 27.9 | 27.3 | 27.9 | 30.0 | 30.2 | | Min-Max | 17.4-39.8 | 17.6-40.0 | 18.0-39.0 | 21.3-36.7 | 20.1-38.4 | 21.8-39.8 | | **Gender (m/n, %)** | | | | | | | | Female | 78/129 (60.5%) | 77/128 (60.2%) | 71/122 (58.2%) | 16/34 (47.1%) | 15/32 (46.9%) | 23/35 (65.7%) | | Male | 51/129 (39.5%) | 51/128 (39.8%) | 51/122 (41.8%) | 18/34 (52.9%) | 17/32 (53.1%) | 12/35 (34.3%) | | **Ethnicity (m/n, %)** | | | | | | | | Hispanic or Latino | 5/129 (3.9%) | 5/123 (4.1%) | 8/115 (7.0%) | 2/32 (6.3%) | 1/29 (3.4%) | 4/34 (11.8%) | | Not Hispanic or Latino | 124/129 (96.1%) | 118/123 (95.9%) | 107/115 (93.0%) | 30/32 (93.8%) | 28/29 (96.6%) | 30/34 (88.2%) | | **Race ** (m/n, %)** | | | | | | | | American Indian or Alaska Native | 0/129 (0.0%) | 0/128 (0.0%) | 0/122 (0.0%) | 0/34 (0.0%) | 0/32 (0.0%) | 0/35 (0.0%) | | Asian | 49/129 (38.0%) | 51/128 (39.8%) | 50/122 (41.0%) | 14/34 (41.2%) | 7/32 (21.9%) | 10/35 (28.6%) | | Black or African American | 10/129 (7.8%) | 5/128 (3.9%) | 9/122 (7.4%) | 1/34 (2.9%) | 2/32 (6.3%) | 4/35 (11.4%) | | Native Hawaiian or Other Pacific Islander | 0/129 (0.0%) | 1/128 (0.8%) | 0/122 (0.0%) | 0/34 (0.0%) | 0/32 (0.0%) | 0/35 (0.0%) | | White | 68/129 (52.7%) | 70/128 (54.7%) | 58/122 (47.5%) | 18/34 (52.9%) | 21/32 (65.6%) | 20/35 (57.1%) | | Other | 2/129 (1.6%) | 2/128 (1.6%) | 5/122 (4.1%) | 1/34 (2.9%) | 2/32 (6.3%) | 1/35 (2.9%) | | **Highest Level of Education Attained (m/n, %)** | | | | | | | | < High School | 38/129 (29.5%) | 39/128 (30.5%) | 37/122 (30.3%) | 8/34 (23.5%) | 6/32 (18.8%) | 9/35 (25.7%) | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 19 of 59 {19} | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | High School | 22/129 (17.1%) | 26/128 (20.3%) | 24/122 (19.7%) | 6/34 (17.6%) | 8/32 (25.0%) | 8/35 (22.9%) | | > High School | 69/129 (53.5%) | 63/128 (49.2%) | 61/122 (50.0%) | 20/34 (58.8%) | 18/32 (56.3%) | 18/35 (51.4%) | | **Primary Payer Source (m/n, %)** | | | | | | | | Medicaid | 8/129 (6.2%) | 4/128 (3.1%) | 5/122 (4.1%) | 0/34 (0.0%) | 2/32 (6.3%) | 2/35 (5.7%) | | Medicare | 31/129 (24.0%) | 39/128 (30.5%) | 25/122 (20.5%) | 8/34 (23.5%) | 10/32 (31.3%) | 12/35 (34.3%) | | Self Pay | 4/129 (3.1%) | 3/128 (2.3%) | 2/122 (1.6%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/35 (0.0%) | | Other | 86/129 (66.7%) | 82/128 (64.1%) | 90/122 (73.8%) | 25/34 (73.5%) | 19/32 (59.4%) | 21/35 (60.0%) | | **Preoperative Working Status (m/n, %)** | | | | | | | | Not Working | 88/129 (68.2%) | 95/128 (74.2%) | 81/122 (66.4%) | 24/34 (70.6%) | 23/32 (71.9%) | 25/35 (71.4%) | | Working | 41/129 (31.8%) | 33/128 (25.8%) | 41/122 (33.6%) | 10/34 (29.4%) | 9/32 (28.1%) | 10/35 (28.6%) | | **Tobacco/Nicotine Usage (m/n, %)** | | | | | | | | Current | 12/129 (9.3%) | 12/128 (9.4%) | 11/122 (9.0%) | 2/34 (5.9%) | 1/32 (3.1%) | 5/35 (14.3%) | | Former | 28/129 (21.7%) | 28/128 (21.9%) | 30/122 (24.6%) | 12/34 (35.3%) | 12/32 (37.5%) | 9/35 (25.7%) | | Never | 89/129 (69.0%) | 88/128 (68.8%) | 81/122 (66.4%) | 20/34 (58.8%) | 19/32 (59.4%) | 21/35 (60.0%) | **Table 7: Summary of demographic information by treatment group based on subjects from OUS** | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | **Age at Randomization (years)** | | | | | | | | Number of Subjects with Data Available (n) | 49 | 51 | 49 | 14 | 7 | 10 | | Mean (SD) | 59.6 (9.3) | 57.9 (11.1) | 56.9 (10.5) | 61.6 (8.5) | 56.5 (14.4) | 61.6 (10.4) | | Median | 60.5 | 57.7 | 56.1 | 59.1 | 57.4 | 62.3 | | Min-Max | 35.0-76.7 | 30.6-77.8 | 30.6-78.3 | 47.8-74.7 | 26.9-68.2 | 39.6-72.0 | | **BMI (kg/m^{2})** | | | | | | | | Number of Subjects with Data Available (n) | 49 | 51 | 49 | 14 | 7 | 10 | | Mean (SD) | 24.3 (3.1) | 25.6 (3.4) | 25.1 (3.4) | 25.9 (2.1) | 26.2 (4.8) | 26.3 (2.6) | | Median | 23.4 | 25.5 | 25.1 | 25.4 | 24.7 | 25.5 | | Min-Max | 17.4-33.2 | 17.6-36.1 | 18.0-32.9 | 23.1-31.8 | 20.1-33.2 | 23.4-30.5 | | **Gender (m/n, %)** | | | | | | | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 20 of 59 {20} | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | Female | 31/49 (63.3%) | 33/51 (64.7%) | 28/49 (57.1%) | 6/14 (42.9%) | 4/7 (57.1%) | 7/10 (70.0%) | | Male | 18/49 (36.7%) | 18/51 (35.3%) | 21/49 (42.9%) | 8/14 (57.1%) | 3/7 (42.9%) | 3/10 (30.0%) | | **Ethnicity (m/n, %)** | | | | | | | | Hispanic or Latino | 0/49 (0.0%) | 0/50 (0.0%) | 0/47 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Not Hispanic or Latino | 49/49 (100%) | 50/50 (100%) | 47/47 (100%) | 14/14 (100%) | 7/7 (100%) | 10/10 (100%) | | **Race ** (m/n, %)** | | | | | | | | American Indian or Alaska Native | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Asian | 49/49 (100%) | 51/51 (100%) | 49/49 (100%) | 14/14 (100%) | 7/7 (100%) | 10/10 (100%) | | Black or African American | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Native Hawaiian or Other Pacific Islander | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | White | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Other | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | **Highest Level of Education Attained (m/n, %)** | | | | | | | | < High School | 31/49 (63.3%) | 34/51 (66.7%) | 33/49 (67.3%) | 8/14 (57.1%) | 4/7 (57.1%) | 6/10 (60.0%) | | High School | 8/49 (16.3%) | 5/51 (9.8%) | 4/49 (8.2%) | 1/14 (7.1%) | 0/7 (0.0%) | 2/10 (20.0%) | | > High School | 10/49 (20.4%) | 12/51 (23.5%) | 12/49 (24.5%) | 5/14 (35.7%) | 3/7 (42.9%) | 2/10 (20.0%) | | **Primary Payer Source (m/n, %)** | | | | | | | | Medicaid | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Medicare | 0/49 (0.0%) | 0/51 (0.0%) | 0/49 (0.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Self Pay | 0/49 (0.0%) | 2/51 (3.9%) | 1/49 (2.0%) | 0/14 (0.0%) | 0/7 (0.0%) | 0/10 (0.0%) | | Other | 49/49 (100%) | 47/51 (92.2%) | 47/49 (95.9%) | 14/14 (100%) | 7/7 (100%) | 10/10 (100%) | | **Preoperative Working Status (m/n, %)** | | | | | | | | Not Working | 41/49 (83.7%) | 43/51 (84.3%) | 41/49 (83.7%) | 12/14 (85.7%) | 6/7 (85.7%) | 10/10 (100%) | | Working | 8/49 (16.3%) | 8/51 (15.7%) | 8/49 (16.3%) | 2/14 (14.3%) | 1/7 (14.3%) | 0/10 (0.0%) | | **Tobacco/Nicotine Usage (m/n, %)** | | | | | | | | Current | 2/49 (4.1%) | 2/51 (3.9%) | 4/49 (8.2%) | 1/14 (7.1%) | 1/7 (14.3%) | 1/10 (10.0%) | | Former | 2/49 (4.1%) | 4/51 (7.8%) | 5/49 (10.2%) | 2/14 (14.3%) | 0/7 (0.0%) | 0/10 (0.0%) | | Never | 45/49 (91.8%) | 45/51 (88.2%) | 40/49 (81.6%) | 11/14 (78.6%) | 6/7 (85.7%) | 9/10 (90.0%) | **Table 8: Summary of demographic information by treatment group based on subjects from US** | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | **Age at Randomization (years)** | | | | | | | | Number of Subjects with Data Available (n) | 80 | 77 | 73 | 20 | 25 | 25 | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 21 of 59 {21} | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | Mean (SD) | 61.7 (10.9) | 64.4 (10.5) | 61.2 (8.5) | 64.1 (7.6) | 62.8 (10.2) | 63.9 (8.1) | | Median | 61.9 | 65.6 | 61.3 | 65.8 | 64.5 | 64.4 | | Min-Max | 32.2-80.8 | 43.1-82.4 | 42.4-77.9 | 50.0-73.4 | 38.4-78.3 | 51.5-78.1 | | **BMI (kg/m^{2})** | | | | | | | | Number of Subjects with Data Available (n) | 80 | 77 | 73 | 20 | 25 | 25 | | Mean (SD) | 30.5 (4.9) | 30.8 (4.7) | 30.3 (4.5) | 29.7 (4.1) | 30.7 (4.5) | 32.6 (4.7) | | Median | 30.8 | 31.0 | 31.2 | 29.0 | 30.8 | 33.3 | | Min-Max | 19.8-39.8 | 20.6-40.0 | 20.3-39.0 | 21.3-36.7 | 21.0-38.4 | 21.8-39.8 | | **Gender (m/n, %)** | | | | | | | | Female | 47/80 (58.8%) | 44/77 (57.1%) | 43/73 (58.9%) | 10/20 (50.0%) | 11/25 (44.0%) | 16/25 (64.0%) | | Male | 33/80 (41.3%) | 33/77 (42.9%) | 30/73 (41.1%) | 10/20 (50.0%) | 14/25 (56.0%) | 9/25 (36.0%) | | **Ethnicity (m/n, %)** | | | | | | | | Hispanic or Latino | 5/80 (6.3%) | 5/73 (6.8%) | 8/68 (11.8%) | 2/18 (11.1%) | 1/22 (4.5%) | 4/24 (16.7%) | | Not Hispanic or Latino | 75/80 (93.8%) | 68/73 (93.2%) | 60/68 (88.2%) | 16/18 (88.9%) | 21/22 (95.5%) | 20/24 (83.3%) | | **Race ** (m/n, %)** | | | | | | | | American Indian or Alaska Native | 0/80 (0.0%) | 0/77 (0.0%) | 0/73 (0.0%) | 0/20 (0.0%) | 0/25 (0.0%) | 0/25 (0.0%) | | Asian | 0/80 (0.0%) | 0/77 (0.0%) | 1/73 (1.4%) | 0/20 (0.0%) | 0/25 (0.0%) | 0/25 (0.0%) | | Black or African American | 10/80 (12.5%) | 5/77 (6.5%) | 9/73 (12.3%) | 1/20 (5.0%) | 2/25 (8.0%) | 4/25 (16.0%) | | Native Hawaiian or Other Pacific Islander | 0/80 (0.0%) | 1/77 (1.3%) | 0/73 (0.0%) | 0/20 (0.0%) | 0/25 (0.0%) | 0/25 (0.0%) | | White | 68/80 (85.0%) | 70/77 (90.9%) | 58/73 (79.5%) | 18/20 (90.0%) | 21/25 (84.0%) | 20/25 (80.0%) | | Other | 2/80 (2.5%) | 2/77 (2.6%) | 5/73 (6.8%) | 1/20 (5.0%) | 2/25 (8.0%) | 1/25 (4.0%) | | **Highest Level of Education Attained (m/n, %)** | | | | | | | | < High School | 7/80 (8.8%) | 5/77 (6.5%) | 4/73 (5.5%) | 0/20 (0.0%) | 2/25 (8.0%) | 3/25 (12.0%) | | High School | 14/80 (17.5%) | 21/77 (27.3%) | 20/73 (27.4%) | 5/20 (25.0%) | 8/25 (32.0%) | 6/25 (24.0%) | | > High School | 59/80 (73.8%) | 51/77 (66.2%) | 49/73 (67.1%) | 15/20 (75.0%) | 15/25 (60.0%) | 16/25 (64.0%) | | **Primary Payer Source (m/n, %)** | | | | | | | | Medicaid | 8/80 (10.0%) | 4/77 (5.2%) | 5/73 (6.8%) | 0/20 (0.0%) | 2/25 (8.0%) | 2/25 (8.0%) | | Medicare | 31/80 (38.8%) | 39/77 (50.6%) | 25/73 (34.2%) | 8/20 (40.0%) | 10/25 (40.0%) | 12/25 (48.0%) | | Self Pay | 4/80 (5.0%) | 1/77 (1.3%) | 1/73 (1.4%) | 1/20 (5.0%) | 1/25 (4.0%) | 0/25 (0.0%) | | Other | 37/80 (46.3%) | 33/77 (42.9%) | 42/73 (57.5%) | 11/20 (55.0%) | 12/25 (48.0%) | 11/25 (44.0%) | | **Preoperative Working Status (m/n, %)** | | | | | | | | Not Working | 47/80 (58.8%) | 52/77 (67.5%) | 40/73 (54.8%) | 12/20 (60.0%) | 17/25 (68.0%) | 15/25 (60.0%) | | Working | 33/80 (41.3%) | 25/77 (32.5%) | 33/73 (45.2%) | 8/20 (40.0%) | 8/25 (32.0%) | 10/25 (40.0%) | | **Tobacco/Nicotine Usage (m/n, %)** | | | | | | | | Current | 10/80 (12.5%) | 10/77 (13.0%) | 7/73 (9.6%) | 1/20 (5.0%) | 0/25 (0.0%) | 4/25 (16.0%) | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 22 of 59 {22} | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | Former | 26/80 (32.5%) | 24/77 (31.2%) | 25/73 (34.2%) | 10/20 (50.0%) | 12/25 (48.0%) | 9/25 (36.0%) | | Never | 44/80 (55.0%) | 43/77 (55.8%) | 41/73 (56.2%) | 9/20 (45.0%) | 13/25 (52.0%) | 12/25 (48.0%) | Baseline clinical endpoints are summarized in **Table 9** for one-level and two-level subjects. There were no statistically significant differences across groups except for Neurological Status where there was a difference in the percentage of patients with abnormal motor functions (Infuse 2.1: 41.2% (14/34), Infuse 4.2: 12.5% (4/32), and Control: 26.5% (9/34) (**Table 9**)). Baseline clinical endpoints are also shown by subjects from OUS sites (**Table 10**) and US sites (**Table 11**). **Table 9: Summary of baseline clinical endpoints by treatment group based on all subjects** | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | **ODI** | | | | | | | | Number of Subjects with Data Available (n) | 129 | 128 | 122 | 34 | 32 | 35 | | Mean (SD) | 54.4 (12.2) | 53.9 (10.6) | 53.4 (11.8) | 52.2 (11.0) | 56.8 (10.0) | 56.5 (12.3) | | Median | 52.0 | 54.0 | 52.0 | 51.1 | 58.0 | 56.0 | | Min-Max | 35.6-84.0 | 36.0-78.0 | 36.0-90.0 | 38.0-76.0 | 36.0-76.0 | 36.0-84.0 | | **Back Pain** | | | | | | | | Number of Subjects with Data Available (n) | 129 | 128 | 122 | 34 | 32 | 35 | | Mean (SD) | 6.6 (2.4) | 6.4 (2.2) | 6.6 (2.1) | 6.8 (2.5) | 7.1 (1.9) | 7.3 (2.1) | | Median | 7.0 | 7.0 | 7.0 | 7.0 | 7.5 | 8.0 | | Min-Max | 1-10 | 1-10 | 1-10 | 2-10 | 2-10 | 3-10 | | **Leg Pain** | | | | | | | | Number of Subjects with Data Available (n) | 129 | 128 | 122 | 34 | 32 | 35 | | Mean (SD) | 7.0 (2.0) | 6.7 (2.0) | 6.6 (2.2) | 7.5 (1.7) | 7.1 (1.8) | 7.7 (1.8) | | Median | 7.0 | 7.0 | 7.0 | 7.0 | 7.5 | 8.0 | | Min-Max | 3-10 | 1-10 | 1-10 | 1-10 | 2-10 | 2-10 | | **Neurological Status** | | | | | | | | Motor Functions (m/n, %) | | | | | | | | Abnormal | 47/129 (36.4%) | 42/126 (33.3%) | 31/122 (25.4%) | 14/34 (41.2%) | 4/32 (12.5%) | 9/34 (26.5%) | | Normal | 82/129 (63.6%) | 84/126 (66.7%) | 91/122 (74.6%) | 20/34 (58.8%) | 28/32 (87.5%) | 25/34 (73.5%) | | Sensory Functions (m/n, %) | | | | | | | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 23 of 59 {23} | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | Abnormal | 41/129 (31.8%) | 43/126 (34.1%) | 39/122 (32.0%) | 15/34 (44.1%) | 9/32 (28.1%) | 8/34 (23.5%) | | Normal | 88/129 (68.2%) | 83/126 (65.9%) | 83/122 (68.0%) | 19/34 (55.9%) | 23/32 (71.9%) | 26/34 (76.5%) | | Reflexes (m/n, %) | | | | | | | | Abnormal | 39/129 (30.2%) | 33/126 (26.2%) | 31/122 (25.4%) | 19/34 (55.9%) | 10/32 (31.3%) | 12/34 (35.3%) | | Normal | 90/129 (69.8%) | 93/126 (73.8%) | 91/122 (74.6%) | 15/34 (44.1%) | 22/32 (68.8%) | 22/34 (64.7%) | | Straight Leg Raise (m/n, %) | | | | | | | | Abnormal | 43/129 (33.3%) | 49/126 (38.9%) | 44/122 (36.1%) | 13/34 (38.2%) | 7/32 (21.9%) | 10/34 (29.4%) | | Normal | 86/129 (66.7%) | 77/126 (61.1%) | 78/122 (63.9%) | 21/34 (61.8%) | 25/32 (78.1%) | 24/34 (70.6%) | Table 10: Summary of baseline clinical endpoints by treatment group based on subjects from OUS | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | **ODI** | | | | | | | | Number of Subjects with Data Available (n) | 49 | 51 | 49 | 14 | 7 | 10 | | Mean (SD) | 54.1 (11.4) | 56.1 (8.5) | 56.5 (10.3) | 54.3 (10.7) | 62.4 (9.7) | 57.5 (14.0) | | Median | 52.0 | 57.8 | 55.6 | 53.7 | 66.0 | 57.0 | | Min-Max | 35.6-82.0 | 37.8-70.0 | 36.0-82.2 | 42.0-75.6 | 50.0-76.0 | 36.0-84.0 | | **Back Pain** | | | | | | | | Number of Subjects with Data Available (n) | 49 | 51 | 49 | 14 | 7 | 10 | | Mean (SD) | 4.8 (2.1) | 5.2 (2.1) | 5.4 (1.9) | 5.9 (2.6) | 6.7 (2.2) | 5.5 (2.1) | | Median | 5.0 | 5.0 | 5.0 | 5.5 | 6.0 | 5.0 | | Min-Max | 1-10 | 1-10 | 1-9 | 2-10 | 3-10 | 3-10 | | **Leg Pain** | | | | | | | | Number of Subjects with Data Available (n) | 49 | 51 | 49 | 14 | 7 | 10 | | Mean (SD) | 6.2 (1.8) | 5.6 (1.8) | 5.8 (2.0) | 6.9 (2.1) | 7.1 (1.2) | 7.7 (1.6) | | Median | 6.0 | 6.0 | 5.0 | 7.0 | 7.0 | 7.5 | | Min-Max | 3-10 | 1-10 | 2-10 | 1-9 | 6-9 | 6-10 | | **Neurological Status** | | | | | | | | Motor Functions (m/n, %) | | | | | | | | Abnormal | 24/49 (49.0%) | 17/51 (33.3%) | 18/49 (36.7%) | 7/14 (50.0%) | 1/7 (14.3%) | 4/10 (40.0%) | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 24 of 59 {24} | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | Normal | 25/49 (51.0%) | 34/51 (66.7%) | 31/49 (63.3%) | 7/14 (50.0%) | 6/7 (85.7%) | 6/10 (60.0%) | | Sensory Functions (m/n, %) | | | | | | | | Abnormal | 23/49 (46.9%) | 19/51 (37.3%) | 19/49 (38.8%) | 10/14 (71.4%) | 3/7 (42.9%) | 3/10 (30.0%) | | Normal | 26/49 (53.1%) | 32/51 (62.7%) | 30/49 (61.2%) | 4/14 (28.6%) | 4/7 (57.1%) | 7/10 (70.0%) | | Reflexes (m/n, %) | | | | | | | | Abnormal | 16/49 (32.7%) | 12/51 (23.5%) | 13/49 (26.5%) | 7/14 (50.0%) | 3/7 (42.9%) | 6/10 (60.0%) | | Normal | 33/49 (67.3%) | 39/51 (76.5%) | 36/49 (73.5%) | 7/14 (50.0%) | 4/7 (57.1%) | 4/10 (40.0%) | | Straight Leg Raise (m/n, %) | | | | | | | | Abnormal | 18/49 (36.7%) | 17/51 (33.3%) | 13/49 (26.5%) | 6/14 (42.9%) | 1/7 (14.3%) | 1/10 (10.0%) | | Normal | 31/49 (63.3%) | 34/51 (66.7%) | 36/49 (73.5%) | 8/14 (57.1%) | 6/7 (85.7%) | 9/10 (90.0%) | Table 11: Summary of baseline clinical endpoints by treatment group based on subjects from US | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | **ODI** | | | | | | | | Number of Subjects with Data Available (n) | 80 | 77 | 73 | 20 | 25 | 25 | | Mean (SD) | 54.7 (12.7) | 52.3 (11.7) | 51.4 (12.3) | 50.8 (11.3) | 55.3 (9.7) | 56.1 (11.8) | | Median | 52.0 | 50.0 | 48.0 | 50.6 | 57.8 | 56.0 | | Min-Max | 36.0-84.0 | 36.0-78.0 | 36.0-90.0 | 38.0-76.0 | 36.0-70.0 | 38.0-80.0 | | **Back Pain** | | | | | | | | Number of Subjects with Data Available (n) | 80 | 77 | 73 | 20 | 25 | 25 | | Mean (SD) | 7.7 (1.8) | 7.1 (1.9) | 7.4 (1.9) | 7.5 (2.3) | 7.2 (1.9) | 8.0 (1.7) | | Median | 8.0 | 7.0 | 8.0 | 8.0 | 8.0 | 8.0 | | Min-Max | 1-10 | 2-10 | 2-10 | 3-10 | 2-10 | 4-10 | | **Leg Pain** | | | | | | | | Number of Subjects with Data Available (n) | 80 | 77 | 73 | 20 | 25 | 25 | | Mean (SD) | 7.6 (1.9) | 7.4 (1.7) | 7.1 (2.1) | 7.9 (1.3) | 7.0 (1.9) | 7.7 (2.0) | | Median | 8.0 | 7.0 | 7.0 | 8.0 | 8.0 | 8.0 | | Min-Max | 3-10 | 2-10 | 1-10 | 6-10 | 2-10 | 2-10 | | **Neurological Status** | | | | | | | | Motor Functions (m/n, %) | | | | | | | | Abnormal | 23/80 (28.8%) | 25/75 (33.3%) | 13/73 (17.8%) | 7/20 (35.0%) | 3/25 (12.0%) | 5/24 (20.8%) | | Normal | 57/80 (71.3%) | 50/75 (66.7%) | 60/73 (82.2%) | 13/20 (65.0%) | 22/25 (88.0%) | 19/24 (79.2%) | | Sensory Functions (m/n, %) | | | | | | | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 25 of 59 {25} | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | Abnormal | 18/80 (22.5%) | 24/75 (32.0%) | 20/73 (27.4%) | 5/20 (25.0%) | 6/25 (24.0%) | 5/24 (20.8%) | | Normal | 62/80 (77.5%) | 51/75 (68.0%) | 53/73 (72.6%) | 15/20 (75.0%) | 19/25 (76.0%) | 19/24 (79.2%) | | Reflexes (m/n, %) | | | | | | | | Abnormal | 23/80 (28.8%) | 21/75 (28.0%) | 18/73 (24.7%) | 12/20 (60.0%) | 7/25 (28.0%) | 6/24 (25.0%) | | Normal | 57/80 (71.3%) | 54/75 (72.0%) | 55/73 (75.3%) | 8/20 (40.0%) | 18/25 (72.0%) | 18/24 (75.0%) | | Straight Leg Raise (m/n, %) | | | | | | | | Abnormal | 25/80 (31.3%) | 32/75 (42.7%) | 31/73 (42.5%) | 7/20 (35.0%) | 6/25 (24.0%) | 9/24 (37.5%) | | Normal | 55/80 (68.8%) | 43/75 (57.3%) | 42/73 (57.5%) | 13/20 (65.0%) | 19/25 (76.0%) | 15/24 (62.5%) | A summary of the surgical indications and key surgical information is provided in **Table 12**. No statistical differences were noted except for the levels treated in the two-level subject group, for the mean length of hospital stay, and distribution of treatment level (**Table 12**). Surgical indications and select surgical information are also shown for OUS (**Table 13**) and US subjects (**Table 14**). **Table 12: Summary of surgical indication and surgical information by treatment group based on all subjects** | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | **Primary Diagnosis (m/n, %)** | | | | | | | | Instability | 46/129 (35.7%) | 53/128 (41.4%) | 46/122 (37.7%) | 8/34 (23.5%) | 7/32 (21.9%) | 8/35 (22.9%) | | Recurrent Disc Herniation | 12/129 (9.3%) | 11/128 (8.6%) | 8/122 (6.6%) | 2/34 (5.9%) | 2/32 (6.3%) | 2/35 (5.7%) | | Stenosis | 71/129 (55.0%) | 64/128 (50.0%) | 68/122 (55.7%) | 24/34 (70.6%) | 23/32 (71.9%) | 25/35 (71.4%) | | **Has the subject had previous lumbar spinal surgery (m/n, %)** | 16/129 (12.4%) | 20/128 (15.6%) | 24/122 (19.7%) | 1/34 (2.9%) | 6/32 (18.8%) | 4/35 (11.4%) | | **Mean (SD) Operation Time, minutes** | 174.1 (66.8) | 175.1 (69.8) | 166.5 (56.4) | 221.4 (43.7) | 221.1 (61.7) | 203.9 (51.2) | | **Mean (SD) Total Estimated Blood Loss (mL)** | 161.3 (148.1) | 157.0 (125.0) | 152.2 (112.0) | 281.8 (159.4) | 265.6 (282.0) | 269.4 (237.9) | | **Mean (SD) Length of Hospital Stay (days)** | 3.4 (2.1) | 3.5 (2.2) | 3.6 (2.6) | 4.7 (2.8) | 3.3 (1.9) | 3.7 (2.4) | | **Treatment Level (m/n, %) *** | | | | | | | | L2-L3 | 0/129 (0.0%) | 1/128 (0.8%) | 0/122 (0.0%) | --- | --- | --- | | L3-L4 | 4/129 (3.1%) | 6/128 (4.7%) | 7/122 (5.7%) | 0/34 (0.0%) | 1/32 (3.1%) | 0/35 (0.0%) | | L4-L5 | 102/129 (79.1%) | 91/128 (71.1%) | 91/122 (74.6%) | 0/34 (0.0%) | 3/32 (9.4%) | 3/35 (8.6%) | | L5-S1 | 23/129 (17.8%) | 30/128 (23.4%) | 21/122 (17.2%) | --- | --- | --- | | L5-L6 | 0/129 (0.0%) | 0/128 (0.0%) | 1/122 (0.8%) | --- | --- | --- | | L2-L3; L3-L4 | --- | --- | --- | 1/34 (2.9%) | 0/32 (0.0%) | 0/35 (0.0%) | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 26 of 59 {26} | Variable | One-Level Subjects (N = 379) | | | Two-Level Subjects (N = 101) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 129) | Infuse 4.2 (N = 128) | Control (N = 122) | Infuse 2.1 (N = 34) | Infuse 4.2 (N = 32) | Control (N = 35) | | L3-L4; L4-L5 | 0/129 (0.0%) | 0/128 (0.0%) | 2/122 (1.6%) | 19/34 (55.9%) | 17/32 (53.1%) | 8/35 (22.9%) | | L4-L5; L5-S1 | --- | --- | --- | 14/34 (41.2%) | 11/32 (34.4%) | 24/35 (68.6%) | | **Surgical Access (m/n, %)** | | | | | | | | Minimally Invasive (i.e. Metrx or Quadrant) | 53/129 (41.1%) | 53/128 (41.4%) | 49/122 (40.2%) | 5/34 (14.7%) | 6/32 (18.8%) | 4/35 (11.4%) | | Open | 76/129 (58.9%) | 75/128 (58.6%) | 73/122 (59.8%) | 29/34 (85.3%) | 26/32 (81.3%) | 31/35 (88.6%) | | **Mean (SD) Volume of Local Bone Autograft Implanted (cc)** | 6.7 (5.3) | 6.1 (4.0) | 7.0 (5.5) | Sup: 8.6 (6.6) Inf: 8.3 (6.1) | Sup: 8.1 (4.9) Inf: 7.5 (4.7) | Sup: 9.0 (5.6) Inf: 10.5 (5.7) | | **Mean (SD) Volume of Allograft Bone Implanted (cc)** | 9.3 (7.6) | 9.8 (7.5) | 11.0 (9.3) | Sup: 8.2 (10.4) Inf: 11.5 (14.1) | Sup: 8.7 (5.7) Inf: 9.2 (5.5) | Sup: 6.9 (3.4) Inf: 8.8 (1.5) | | * Two subjects were randomized as one-level subject, but two levels were treated, seven subjects were randomized as two-level subjects, but only one level was treated. | | | | | | | **Table 13: Summary of surgical indication and surgical information by treatment group based on subjects from OUS** | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | **Primary Diagnosis (m/n, %)** | | | | | | | | Instability | 16/49 (32.7%) | 18/51 (35.3%) | 16/49 (32.7%) | 0/14 (0.0%) | 0/7 (0.0%) | 2/10 (20.0%) | | Recurrent Disc Herniation | 1/49 (2.0%) | 3/51 (5.9%) | 2/49 (4.1%) | 1/14 (7.1%) | 1/7 (14.3%) | 0/10 (0.0%) | | Stenosis | 32/49 (65.3%) | 30/51 (58.8%) | 31/49 (63.3%) | 13/14 (92.9%) | 6/7 (85.7%) | 8/10 (80.0%) | | **Has the subject had previous lumbar spinal surgery (m/n, %)** | 2/49 (4.1%) | 3/51 (5.9%) | 3/49 (6.1%) | 1/14 (7.1%) | 1/7 (14.3%) | 0/10 (0.0%) | | **Mean (SD) Operation Time, minutes** | 176.2 (66.9) | 173.5 (66.6) | 169.2 (54.7) | 219.3 (56.5) | 214.4 (43.0) | 180.7 (47.2) | | **Mean (SD) Total Estimated Blood Loss (mL)** | 191.8 (96.7) | 196.7 (89.1) | 204.3 (89.0) | 350.7 (158.9) | 400.0 (152.8) | 285.0 (137.5) | | **Mean (SD) Length of Hospital Stay (days)** | 5.0 (1.2) | 4.8 (1.1) | 5.2 (1.2) | 6.9 (2.7) | 5.7 (1.3) | 5.3 (1.6) | | **Treatment Level (m/n, %) *** | | | | | | | | L3-L4 | 1/49 (2.0%) | 0/51 (0.0%) | 2/49 (4.1%) | --- | --- | --- | | L4-L5 | 36/49 (73.5%) | 36/51 (70.6%) | 35/49 (71.4%) | 0/14 (0.0%) | 1/7 (14.3%) | 0/10 (0.0%) | | L5-S1 | 12/49 (24.5%) | 15/51 (29.4%) | 10/49 (20.4%) | --- | --- | --- | | L5-L6 | 0/49 (0.0%) | 0/51 (0.0%) | 1/49 (2.0%) | --- | --- | --- | | L3-L4; L4-L5 | 0/49 (0.0%) | 0/51 (0.0%) | 1/49 (2.0%) | 8/14 (57.1%) | 5/7 (71.4%) | 2/10 (20.0%) | | L4-L5; L5-S1 | --- | --- | --- | 6/14 (42.9%) | 1/7 (14.3%) | 8/10 (80.0%) | | **Surgical Access (m/n, %)** | | | | | | | | Minimally Invasive (i.e. Metrx or Quadrant) | 16/49 (32.7%) | 19/51 (37.3%) | 17/49 (34.7%) | 1/14 (7.1%) | 1/7 (14.3%) | 0/10 (0.0%) | | Open | 33/49 (67.3%) | 32/51 (62.7%) | 32/49 (65.3%) | 13/14 (92.9%) | 6/7 (85.7%) | 10/10 (100%) | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 27 of 59 {27} | Variable | One-Level Subjects (N = 149) | | | Two-Level Subjects (N = 31) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 49) | Infuse 4.2 (N = 51) | Control (N = 49) | Infuse 2.1 (N = 14) | Infuse 4.2 (N = 7) | Control (N = 10) | | Mean (SD) Volume of Local Bone Autograft Implanted (cc) | 5.6 (5.0) | 5.2 (4.1) | 5.5 (4.5) | Sup: 6.6 (6.1) Inf: 7.8 (7.0) | Sup: 5.7 (3.4) Inf: 6.0 (5.2) | Sup: 9.0 (8.2) Inf: 12.9 (9.3) | | Mean (SD) Volume of Allograft Bone Implanted (cc) | 2.0 (0.0) | 3.2 (1.8) | 2.7 (0.7) | Sup: 3.3 (1.4) Inf: 1.0 (NA) | Sup: 4.7 (1.5) Inf: 3.0 (NA) | Sup: 5.3 (3.1) Inf: 8.0 (NA) | | * One subject was randomized as one-level subject, but two levels were treated; One subject was randomized as two-level subjects, but only one level was treated; | | | | | | | Table 14: Summary of surgical indication and surgical information by treatment group based on subjects from US | Variable | One-Level Subjects (N = 230) | | | Two-Level Subjects (N = 70) | | | | --- | --- | --- | --- | --- | --- | --- | | | Infuse 2.1 (N = 80) | Infuse 4.2 (N = 77) | Control (N = 73) | Infuse 2.1 (N = 20) | Infuse 4.2 (N = 25) | Control (N = 25) | | Primary Diagnosis (m/n, %) | | | | | | | | Instability | 30/80 (37.5%) | 35/77 (45.5%) | 30/73 (41.1%) | 8/20 (40.0%) | 7/25 (28.0%) | 6/25 (24.0%) | | Recurrent Disc Herniation | 11/80 (13.8%) | 8/77 (10.4%) | 6/73 (8.2%) | 1/20 (5.0%) | 1/25 (4.0%) | 2/25 (8.0%) | | Stenosis | 39/80 (48.8%) | 34/77 (44.2%) | 37/73 (50.7%) | 11/20 (55.0%) | 17/25 (68.0%) | 17/25 (68.0%) | | Has the subject had previous lumbar spinal surgery (m/n, %) | 14/80 (17.5%) | 17/77 (22.1%) | 21/73 (28.8%) | 0/20 (0.0%) | 5/25 (20.0%) | 4/25 (16.0%) | | Mean (SD) Operation Time, minutes | 172.8 (67.2) | 176.0 (72.3) | 164.7 (57.8) | 222.8 (33.5) | 223.0 (66.6) | 213.2 (50.7) | | Mean (SD) Total Estimated Blood Loss (mL) | 142.6 (170.1) | 130.6 (138.4) | 117.2 (112.8) | 233.5 (144.6) | 228.0 (300.3) | 263.2 (270.0) | | Mean (SD) Length of Hospital Stay (days) | 2.4 (1.8) | 2.6 (2.3) | 2.5 (2.7) | 3.2 (1.6) | 2.6 (1.5) | 3.0 (2.4) | | Treatment Level (m/n, %) * | | | | | | | | L2-L3 | 0/80 (0.0%) | 1/77 (1.3%) | 0/73 (0.0%) | --- | --- | --- | | L3-L4 | 3/80 (3.8%) | 6/77 (7.8%) | 5/73 (6.8%) | 0/20 (0.0%) | 1/25 (4.0%) | 0/25 (0.0%) | | L4-L5 | 66/80 (82.5%) | 55/77 (71.4%) | 56/73 (76.7%) | 0/20 (0.0%) | 2/25 (8.0%) | 3/25 (12.0%) | | L5-S1 | 11/80 (13.8%) | 15/77 (19.5%) | 11/73 (15.1%) | --- | --- | --- | | L2-L3; L3-L4 | --- | --- | --- | 1/20 (5.0%) | 0/25 (0.0%) | 0/25 (0.0%) | | L3-L4; L4-L5 | 0/80 (0.0%) | 0/77 (0.0%) | 1/73 (1.4%) | 11/20 (55.0%) | 12/25 (48.0%) | 6/25 (24.0%) | | L4-L5; L5-S1 | --- | --- | --- | 8/20 (40.0%) | 10/25 (40.0%) | 16/25 (64.0%) | | Surgical Access (m/n, %) | | | | | | | | Minimally Invasive (i.e. Metrx or Quadrant) | 37/80 (46.3%) | 34/77 (44.2%) | 32/73 (43.8%) | 4/20 (20.0%) | 5/25 (20.0%) | 4/25 (16.0%) | | Open | 43/80 (53.8%) | 43/77 (55.8%) | 41/73 (56.2%) | 16/20 (80.0%) | 20/25 (80.0%) | 21/25 (84.0%) | | Mean (SD) Volume of Local Bone Autograft Implanted (cc) | 7.3 (5.4) | 6.7 (3.9) | 8.0 (5.9) | Sup: 9.9 (6.7) Inf: 8.6 (5.7) | Sup: 8.7 (5.1) Inf: 7.9 (4.6) | Sup: 9.0 (4.2) Inf: 9.7 (3.9) | | Mean (SD) Volume of Allograft Bone Implanted (cc) | 10.2 (7.5) | 11.1 (7.5) | 13.0 (9.3) | Sup: 17.8 (14.6) Inf: 16.8 (15.2) | Sup: 10.3 (6.0) Inf: 10.4 (5.1) | Sup: 7.8 (3.5) Inf: 9.0 (1.7) | | * One subject was randomized as one-level subject, but two levels were treated; six subjects were randomized as two-level subjects, but only one level was treated. | | | | | | | PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 28 of 59 {28} # D. Safety and Effectiveness Results # 1. Safety Results The analysis of safety for PMA application was based on the “As Treated” (AT) cohort at 24 months after operative intervention. For the PMA application analysis, the AT cohort (N = 480) was comprised of 384 1-level subjects and 96 2-level subjects. The 1-level subjects had 129, 132 and 123 subjects in the 2.1 mg, 4.2 mg, and control cohorts. The 2-level subjects had 34, 28 and 34 subjects in the 2.1 mg, 4.2 mg, and control cohorts. The 24 month follow up rate of the AT population pooled by levels from all sites at the time of this interim analysis for PMA application review was 62.2% one-level patients and 62.5% two-level patients. Adverse events were reviewed and adjudicated for relatedness and severity by an independent clinical events committee (CEC). Cumulative rate of adverse events at the time of PMA application are reported in Table 15 to Table 28. # Adverse events that occurred in the PMA clinical study For one-level subjects, the 24-month cumulative AE rate was 88.6% in the Infuse 2.1 mg group, 89.8% in the Infuse 4.2 mg group, and 87.5% in the Control group (Table 15). There were no statistically significant differences in the 24-month cumulative AE rates between the Infuse groups (2.1 mg or 4.2 mg) and Control group for cumulative AE rate (Table 15, Table 17). For one-level subjects, the 24-month cumulative SAE rate was 27.2% in the Infuse 2.1 mg group, 41.3% in the Infuse 4.2 mg group, and 24.6% in the Control group (Table 15). The 24-month cumulative rate of procedure related SAEs was 11.2% for the Infuse 2.1 mg group, 19% for the Infuse 4.2 mg group, and 8.3% for the Control group for a statistically significant difference in procedure related SAEs for the 4.2 mg group at 24 months after operative intervention compared to the control (p=0.032) (Table 15). When compared to control at 24 months for the 1-level subjects, the Infuse 4.2 mg group had a statistically significantly higher number of SAEs classified as “musculoskeletal and connective tissue disorders” (p = 0.017) and “general disorders and administration site conditions” (p = 0.008) (Table 19, Table 23, Table 27). Otherwise, for one-level subjects at 24 months, there were no other statistically significant differences amongst the 2.1 mg, 4.2 mg, and control groups for AEs or SAEs related to surgical construct, or for AEs or SAEs related to study procedure for the 2.1 mg group compared to control, or for AEs related to study procedure for the 4.2 mg group compared to control (Table 21, Table 23, Table 25, Table 27). Reported adverse events of heterotopic ossification (HO) were captured under the MedDRA Preferred Terms extra skeletal ossification, vertebral osteophyte, or exostosis. Eleven AEs in 10 subjects (3 events in 3 subjects in the Infuse 2.1 mg group, 6 events in 5 subjects in the Infuse 4.2 mg group, and 2 events in 2 subjects in the PMA P000058/S096: FDA Summary of Safety and Effectiveness Data 29 of 59 {29} Control group) reported under these Preferred Terms were adjudicated by the Clinical Events Committee (CEC) to be “related” to the bone graft material. Seven of these events were radiographic observations of HO in subjects who had no clinical sequelae. One subject (Infuse 4.2 mg group) experienced radiculopathy classified as a serious adverse event (S…