OsteoAdapt SP Advanced Bone Graft Feasibility Study - Transforaminal Interbody Lumbar Fusion

Study Overview
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Brief Summary
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The purpose of this clinical study is to assess the safety and effectiveness of the OsteoAdapt SP as a replacement for the autograft standard of care bone graft within the interbody cage, as well as identify the OsteoAdapt SP dose to be investigated in a future pivotal study.

Detailed Description
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This Feasibility Study is a prospective, blinded, controlled, dose-randomized, multicenter, investigational study to evaluate the safety and effectiveness of the OsteoAdapt SP in single-level TLIF procedures for the treatment of symptomatic degenerative diseases of the lumbosacral spine. Patients undergoing elective unilateral, single-level, single interbody cage TLIF who have had at least 6 months of conservative care, met the inclusion criteria and none of the exclusion criteria, and sign the patient informed consent will be screened for enrollment and treated consistent with current TLIF surgical standard of care except that the autograft bone graft component within the interbody cage will be replaced with OsteoAdapt SP. Patients will be randomized to receive OsteoAdapt SP at one of two available concentrations (0.8 mg/cc or 2 mg/cc) with   25-26 patients in each group, or the control group consisting of another  25-26 patients for a total of  75-80 patients. Standard lottery randomization will be used with equal weight in each of the three groups. The investigational group will use the randomized concentration of OsteoAdapt SP within the interbody cage and placement of autograft anterior (or laterally within the disc space) to the cage if desired by the investigator. Control subjects will have autograft harvested from the local site and utilized both inside and anterior (or lateral) to the interbody cage with the option of banked mineralized frozen allograft to supplement if there is not enough local autograft available.

Official Title
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OsteoAdapt SP Feasibility Study A Prospective, Blinded, Controlled, Dose-Randomized Clinical Investigation of OsteoAdapt SP in Transforaminal Lumbar Interbody Fusion in Treatment of Symptomatic Degenerative Disease of The Lumbosacral Spine

Conditions
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Degenerative Disc Disease, Degenerative Spondylolisthesis, Spinal Stenosis, Spine Disease, Lumbar Radiculopathy, Lumbar Spinal Stenosis, Lumbar Disc Herniation, Lumbar Disc Disease, Lumbar Spine Degeneration, Lumbar Spondylolisthesis

Intervention / Treatment
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* Device: OsteoAdapt SP
* Other: Local Autograft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female age 18-80 (inclusive) at time of signing informed consent and skeletally mature (as determined by physician's assessment of AP lumbar Xray utilizing the Risser Classification method of the iliac crest growth plates) (See addendum 1 for a definitive reference on skeletal age); Subject is planning to undergo a unilateral, single-level, single interbody cage, TLIF procedure (from L2-S1 with posterior supplemental fixation) with a primary diagnosis of symptomatic lumbar degeneration including back and/or radicular pain with or without foraminal or recess stenosis confirmed by patient history, physical examinations, and radiographic imaging (xray, CT, MRI) with no more than Grade 2 Spondylolisthesis with one or more of the following factors: Instability as defined by >/-3mm translation or >/-5° angulation; Osteophyte formation of facet joints or vertebral endplates; Decreased disc height, on average by >2mm, but dependent upon the spinal level; Scarring/thickening of ligamentum flavum, annulus fibrosis, or facet joint capsule; Herniated nucleus pulposus; facet joint degeneration/changes; and/or Vacuum phenomenon. Preoperative ODI score ≥40 at pre-op/baseline; Preoperative back and/or leg pain score of ≥4 (out of 10); Failed ≥6 months non-operative/conservative treatment (e.g., physical therapy, bracing, traction, medication, TENS, and/or spinal injections; Is willing and able to be present for routine follow up visits, comply with postoperative management program, and is able to understand and sign the informed consent form. Exclusion Criteria: Patient requires spinal fusion surgical procedure (TLIF) at more than one level (non-fusion surgery at the non-index levels, including discectomy and/or single level foraminotomy or laminectomy, is allowed) Prior spinal fusion surgical procedure at the involved or adjacent spinal levels, or non-fusion stabilizing surgeries, e.g., interlaminar devices, dynamic stabilization, or disc replacements. (Prior non-fusion surgery at the target levels, including discectomy and/or single level foraminotomy or laminectomy, is allowed.) Greater than Grade 2 Spondylolisthesis; Planned use of an internal or external bone growth stimulator; Osteoporosis to a degree that spinal instrumentation is contraindicated or a history of a traumatic vertebral fracture. All patients complete SCORE/MORE to assess the need for DEXA scan. If DEXA is required, patients with a T score </- 2.5 will be excluded. A prior DEXA can be used if performed within 9 months pre-op; Morbidly obese, as defined by a Body Mass Index (BMI) >40; Overt or active bacterial infection, either local or systemic; The subject uses, or has used within 30 days of surgery, tobacco or nicotine or is prescribed steroids such as cortisone; (subjects will undergo a nicotine test during screening procedures utilizing a standard commercial cotinine urine dip test; Example: Easy@Home Nicotine Cotinine Urine Panel Dip Test Strips Kit- Sensitive (healthcare-manager.com) Comorbidities precluding subject from being a surgical candidate; Systemic disease including Lupus disease, Reiter's disease, Rheumatoid disease, AIDS, HIV, hepatitis, or autoimmune disease that requires immunosuppressive therapy, including biologics, for systemic inflammation. History of malignancy, radiotherapy, or chemotherapy for any malignancy within the last 5 years. History of malignancy may include multiple exostoses syndrome ((also known as multiple osteochondromas syndrome), an inherited condition associated with bumps of cartilage on the bones, has been associated with an increased risk of chondrosarcoma); individuals who have undergone any transplant surgery and are on immunosuppressant therapy. Has history of any endocrine or metabolic disorder known to affect osteogenesis (e.g.: Paget's disease, renal osteodystrophy, Ehler-Danlos syndrome, or osteogenesis imperfecta); Insulin dependent diabetes; History of exposure to any recombinant proteins or peptides used for bone formation (i.e., Infuse Bone Graft, AUGMENT Bone Graft, GEM21S, i-FACTOR Peptide Enhanced Bone Graft, or PepGen P-15 Synthetic Bone Graft); Hypersensitivity or allergy to any components of the study treatments including, but not limited to, bone morphogenetic proteins (BMPs); tricalcium phosphate (TCP); PLGA polymer; and/or instrumentation materials (titanium, titanium alloy, PEEK). History of any allergy resulting in anaphylaxis; Is a prisoner; Is mentally incompetent. If questionable, obtain psychiatric consult; History of substance abuse (substance abuse defined by DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) code. Criteria for substance abuse defined in Addendum 2. Involved in litigation for spine injury or worker's compensation case; Treatment with an investigational therapy (drug, device, and/or biologic) within 120 days prior to implantation surgery, or such treatment is planned during the 24-month period following implantation of the study treatment; prior or planned use of rhBMP-2. Pregnant (or interested in becoming pregnant in the next 24 months) or nursing. Any condition that would interfere with the subject's ability to comply with study instructions or prohibit MRI/CT/Radiographic assessments that might confound the interpretation of the study or put the subject at risk. Patients with any positive pregnancy test. Tests will be administered at the surgical center prior to surgery. Patient currently taking any drug known to interfere with bone/soft tissue healing. See Medication Protocol section of the Investigator's Brochure. Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study. requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a prospective, dose randomized, controlled, blinded, multicenter, investigational study. Patients undergoing elective unilateral, single-level, single interbody cage TLIF who have had at least 6 months of conservative care will be screened for enrollment. Patients who meet the study entry criteria and sign the patient informed consent form will be enrolled. Patients will be randomized via lottery randomization to receive either OsteoAdapt SP at one of two available concentrations (0.8 mg/cc and 2mg/cc) or the control group (Standard of Care TLIF with autograft). Each group will consist of 25-26 patients for a total of 75-80 patients enrolled.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose OsteoAdapt SP (0.8 mg/cc AMP2/OsteoAdapt SP)<br>Participants will receive a Transforaminal Lumbar Interbody Fusion with OsteoAdapt SP Low Dose (0.8mg/cc AMP2/OsteoAdapt SP) inside the interbody fusion cage with the availability of having local autograft placed anterior/lateral to the cage within the disc space. | Device: OsteoAdapt SP<br>* OsteoAdapt SP is a combination of AMP2 protein bound to an osteoconductive carrier matrix, ReBOSSIS-J. OsteoAdapt SP is a combination of AMP2 protein bound to an osteoconductive carrier matrix, ReBOSSIS-J. AMP2 is a recombinant variant of a naturally occurring human protein, rhBMP2, that has been modified to allow very tight binding to β-TCP and similar ceramics. AMP2 is osteoinductive, meaning that the protein stimulates new bone formation at the site of implantation through the same intracellular signaling process as rhBMP2. ReBOSSIS-J is a synthetic, resorbable bone void filler. ReBOSSIS-J is flexible and can easily fill defects of different sizes using appropriate amounts of the device. The combination product, OsteoAdapt SP, is hydrated at the time of surgery with saline and placed into the interbody fusion cage.<br>|
| Experimental: High Dose OsteoAdapt SP (2.0 mg/cc AMP2/OsteoAdapt SP)<br>Participants will receive a Transforaminal Lumbar Interbody Fusion with OsteoAdapt SP Low Dose (2.0 mg/cc AMP2/OsteoAdapt SP) inside the interbody fusion cage with the availability of having local autograft placed anterior/lateral to the cage within the disc space. | Device: OsteoAdapt SP<br>* OsteoAdapt SP is a combination of AMP2 protein bound to an osteoconductive carrier matrix, ReBOSSIS-J. OsteoAdapt SP is a combination of AMP2 protein bound to an osteoconductive carrier matrix, ReBOSSIS-J. AMP2 is a recombinant variant of a naturally occurring human protein, rhBMP2, that has been modified to allow very tight binding to β-TCP and similar ceramics. AMP2 is osteoinductive, meaning that the protein stimulates new bone formation at the site of implantation through the same intracellular signaling process as rhBMP2. ReBOSSIS-J is a synthetic, resorbable bone void filler. ReBOSSIS-J is flexible and can easily fill defects of different sizes using appropriate amounts of the device. The combination product, OsteoAdapt SP, is hydrated at the time of surgery with saline and placed into the interbody fusion cage.<br>|
| Active Comparator: Control (Standard of Care - Autograft/Mineralized Allograft)<br>Patients will follow standard of care Transforaminal Lumbar Interbody Fusion in which local autograft will be placed inside the interbody fusion cage with the availability of mineralized, frozen, banked, allograft to be placed anterior/lateral to the cage. | Other: Local Autograft<br>* For control arm, local autograft will be utilized inside the interbody cage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Subjects requiring Secondary Surgical Interventions within 24 months post-op. | No secondary surgical interventions, due to fusion failure or non- union, including reoperation, supplemental fixation, removal, or revision of the Investigational Device within the study follow up timeframe of 24 months. | up to 24 months post op | 
| Neurological Status assessed via Motor, Sensory, and Reflex physical exams with outcome measures of normal, abnormal or unknown. Success defined as maintenance or improvement compared to baseline assessment. | • Maintenance or improvement in neurological status affected by the index level at 24 months post-op as compared to baseline measures, as adjudicated by the Medical Monitor. | Baseline compared to 24 months post op | 
| Oswestry Disability Index - Measured on a scale of 0-100 points, 0 being least physically impaired for day to day activities and 100 being extremely difficult or impossible to perform day to day activities. | • Oswestry Disability Index will be compared at 24 months post-op to baseline measures based on a scale of 0-100 points (0 = not physically impaired for day to day activities; 100= severe impairment of day to day activities) Adjacent level progression of pathology will be assessed for any failures of this criteria and adjudicated by the Medical Monitor. | Baseline compared to 24 months post op | 
| Numeric Pain Rating Scale - Pain scale measured on a scale from 0 to 10 (0=no pain; 10 = pain as bad as it can be) compared at 24 months post op to baseline assessment. | • Assessment of the Numeric Pain Rating Scale (NPRS) for back and/or leg pain and defined on a scale of 0 to 10 (0 =no pain; 10 = pain as bad as it can be) Pain scores will be compared at 24 months to baseline values. Adjacent level progression of pathology will be assessed for any failures of this criteria and adjudicated by the Medical Monitor. | Baseline compared to 24 months post op | 
| Radiographic Fusion Assessment - assessed by CT at 12- and 24-months post op as bridging bone from endplate to endplate. | • Radiographic fusion as defined below within 24 months post-op: Presence of Bridging Bone (CT) in at least one of the following locations: Interbody space; or anterior, lateral, or posterior to interbody fusion device. Bridging bone is defined as continuous evidence of bridging bone, whether it be a thin line, or a thicker column of bone; AND No evidence of motion as defined by less than 3mm translational motion and less than 5° in angular motion at each treated level. No radiological evidence of bridging bone in adjacent levels. | Assessed at 24 months post op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS short form, validated, quality of life questionnaire to assess subjects overall mental and general health through a series of 12 questions regarding depression, anxiety, and general health. | • Assess the subject's health related overall quality of life through the PROMIS Short Form Questionnaire. | 24 months post op | 
| Assessment for Immunogenic effects (e.g., anti BMP-2) caused by rhBMP2 antibodies as detected in subject's blood serum through antibody assays. | Assessment for Immunogenic effects (e.g., anti BMP-2) through BMP2 antibody and neutralizing antibody assays. | Pre-op to 24 months (if applicable) | 
| Disc height assessment at the operative level as determined by plain Xray radiographs at each study timepoint. | Disc height assessment at the operative level through radiographic analysis | Pre-op, 6 weeks, 3 months, 6 months, 12 months, 24 months |