CarboClear Pedicle Screw System
Phase: NA
Conditions: Degenerative Disc Disease, Spondylolisthesis, Grade 1
Sponsor: CarboFix Orthopedics Ltd.

  
 
 
 
 
 
 
 
 
CARBOCLEAR PEDICLE  
SCREW SYSTEM 
 
CLINICAL STUDY PROTOCOL 
 
 
 
May 2017 
 
 
CONFIDENTIAL 

                                                                                                                         
 
 
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TABLE OF CONTENTS 
1. 
GENERAL ........................................................................................................................................ 4 
1.1. 
STUDY SPONSOR ........................................................................................................................... 4 
1.2. 
INVESTIGATIONAL DEVICE MANUFACTURER ...................................................................... 4 
1.3. 
INVESTIGATOR AND INVESTIGATION SITE ........................................................................... 4 
1.4. 
STUDY MONITOR .......................................................................................................................... 5 
1.5. 
PROTOCOL SIGNATURES ............................................................................................................ 5 
2. 
CLINICAL STUDY SYNOPSIS ...................................................................................................... 6 
3. 
INTRODUCTION ........................................................................................................................... 12 
4. 
DEVICE DESCRIPTION ................................................................................................................ 16 
4.1 
DEVICE INTENDED USE/INDICATIONS FOR USE .................................................................. 16 
4.2 
SYSTEM DESCRIPTION ............................................................................................................... 16 
4.2.1 
IMPLANT DESCRIPTION ............................................................................................................ 16 
4.2.2 
SURGICAL INSTRUMENTS ........................................................................................................ 22 
4.2.3 
PRINCIPLES OF OPERATION ..................................................................................................... 27 
5. 
INVESTIGATIONAL PLAN .......................................................................................................... 28 
5.1 
PURPOSE ....................................................................................................................................... 28 
5.1.1 
OUTCOME MEASURES ............................................................................................................... 28 
5.2 
STUDY DESIGN ............................................................................................................................ 28 
5.2.1 
LITERATURE CONTROL ............................................................................................................. 31 
5.3 
INCLUSION CRITERIA ................................................................................................................ 48 
5.4 
EXCLUSION CRITERIA ............................................................................................................... 49 
5.5 
NUMBER OF PATIENTS AND PATIENT SELECTION ............................................................. 51 
5.6 
STUDY SITES ................................................................................................................................ 52 
5.7 
STUDY DURATION ...................................................................................................................... 52 
5.8 
MISSING DATA ............................................................................................................................. 53 
5.9 
PROCEDURES ............................................................................................................................... 54 
5.9.1 
PREOPERATIVE MANAGEMENT .............................................................................................. 54 
5.9.2 
SURGICAL PROCEDURE ............................................................................................................ 55 
5.9.3 
POSTOPERATIVE MANAGEMENT............................................................................................ 55 
5.10 
EVALUATION OF PRIMARY OUTCOME MEASURES ............................................................ 59 
5.10.1 
FUSION EVALUATION ................................................................................................................ 59 
5.10.2 
PAIN AND FUNCTION EVALUATION ...................................................................................... 62 
5.10.3 
SAFETY EVALUATION ............................................................................................................... 63 
5.11 
EVALUATION OF SECONDARY OUTCOME MEASURES ...................................................... 66 
5.12 
STUDY SUCCESS CRITERIA ....................................................................................................... 67 
5.13 
STATISTICAL ANALYSIS ........................................................................................................... 70 

                                                                                                                         
 
 
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5.13.1 
SAMPLE SIZE JUSTIFICATION .................................................................................................. 70 
5.13.2 
POOLABILITY OF DATA ............................................................................................................. 71 
5.13.3 
ANALYSIS POPULATIONS ......................................................................................................... 73 
5.13.4 
STATISTICAL ANALYSIS OF DATA ......................................................................................... 73 
5.14 
SUMMARY OF RISK ANALYSIS ................................................................................................ 75 
5.14.1 
POSSIBLE HAZARDS ................................................................................................................... 75 
5.14.2 
RISK REDUCTION MEASURES .................................................................................................. 78 
5.14.3 
POTENTIAL BENEFITS ................................................................................................................ 90 
5.14.4 
ADVERSE EVENTS ...................................................................................................................... 90 
5.15 
INFORMED CONSENT ............................................................................................................... 106 
5.16 
CASE REPORT FORMS............................................................................................................... 107 
5.17 
CONFIDENTIALITY ................................................................................................................... 107 
5.18 
MONITORING ............................................................................................................................. 108 
5.19 
OPERATIONAL ISSUES ............................................................................................................. 113 
5.19.1 
TRAINING .................................................................................................................................... 113 
5.19.2 
SUPPLY AND STORAGE (ACCOUNTABILITY) ..................................................................... 113 
5.19.3 
TRACEABILITY OF DEVICES AND DOCUMENTS ............................................................... 114 
5.19.4 
RECORD RETENTION ................................................................................................................ 114 
5.19.5 
AMENDMENTS ........................................................................................................................... 115 
5.19.6 
DEVIATIONS FROM PROTOCOL ............................................................................................. 115 
5.19.7 
PUBLICATION ............................................................................................................................ 116 
 
 APPENDICES…………………………………………………………………….………....…..117 
 
 
Confidentiality Statement 
This Investigational Protocol contains confidential information for the sole information 
and use of the principal investigator and its designated representatives participating in 
this clinical investigation, and the IRB/EC. It should be held confidential and 
maintained in a secure location. It should not be copied or made available for review by 
any unauthorized person or firm. 
 
 

                                                                                                                         
 
 
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1. 
GENERAL 
1.1. 
STUDY SPONSOR 
The proposed study for the CarboClear Pedicle Screw System will be sponsored by: 
 
Sponsor Name: 
CarboFix Orthopedics, Inc. 
Address: 
7183 Beach Drive SW, Ste 1, Ocean Isle Beach, NC 28469, USA 
Tel: 
1-800-4080120; 910-208-9406 
Fax: 
877-705-3567 
E-Mail: 
 hila@carbo-fix.com 
 
1.2. 
INVESTIGATIONAL DEVICE MANUFACTURER 
Sponsor Name: 
CarboFix Orthopedics Ltd. 
Address: 
11 Ha'Hoshlim Street, Herzeliya 4672411, Israel 
Tel: 
Tel: +972-9-9511511 
Fax: 
Fax: +972-9-9548939 
E-Mail: 
hila@carbo-fix.com 
 
1.3. 
INVESTIGATOR AND INVESTIGATION SITE 
Investigator Name: 
 
Investigator Position: 
 
Investigation Site: 
 
Address: 
 
Tel: 
 
Fax: 
 
E-Mail: 
 
 

                                                                                                                         
 
 
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1.4. 
STUDY MONITOR 
Monitoring of the study at US sites will be performed by the following Clinical Research 
Associate (CRA): 
CRA Name: 
Colleen Smith CCS Research, Inc. 
 
 
CCS Research, Inc., Massachusetts, USA 
E-Mail: 
Colleen@carbo-fix.com 
 
 
 
1.5. 
PROTOCOL SIGNATURES 
Sponsor Representative: 
 
 
Name 
 
Title 
 
Signature 
 
Date 
 
 
Investigator: 
I have read this Protocol and agree to adhere to the requirements. I will provide copies of 
this Protocol and all pertinent information to all site personnel involved in this study. I will 
discuss this material with them and ensure they are fully informed regarding the 
investigational product and the conduct of the study. 
 
 
 
Name 
 
Title 
 
Signature 
 
Date 
 
 

                                                                                                                         
 
 
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2. 
CLINICAL STUDY SYNOPSIS    
Device Name: 
 
CarboClear Pedicle Screw System ("CarboClear System").  
  
Regulatory Status: 
Investigational 
Device; 
Exclusively 
for 
use 
in 
clinical 
investigations. 
 
Study Design: 
A prospective, multi-center, confirmatory, single arm, study. 
Results of the study will be compared to data from the literature. 
 
Purpose: 
To demonstrate the safety and effectiveness of the CarboClear 
System, for skeletally mature DDD patients undergoing one level 
spinal fusion in combination with interbody fusion device, and 
requiring immediate, rigid, posterior spinal stabilization of the 
lumbar and/or sacral spine.  
 
Intended Use: 
The CarboClear Pedicle Screw System is intended to provide rigid 
immobilization and stabilization of lumbar and/or sacral segments 
as an adjunct to fusion in patients with degenerative disc disease 
(DDD) at one level from L2 to S1, with up to Grade I 
spondylolisthesis. DDD is defined as back pain of discogenic origin 
with degeneration of the disc confirmed by history and radiographic 
studies. Patients should be skeletally mature and have at least six 
months of non-operative treatment. 
The CarboClear Pedicle Screw System is designed for use with 
intervertebral body fusion device and with autogenous and/or 
allogenic 
bone 
graft 
comprised 
of 
cancellous 
and/or 
corticocancellous bone graft.  
 
Procedure: 
Implantation of the investigational device and an FDA cleared 
PEEK interbody fusion device (either Medtronic's Capstone PEEK 
Spinal System, or Medtronic's Crescent PEEK Spinal System), 
using PLIF or TLIF. Posterolateral spinal fusion may also be 
performed, according to the physician discretion, using autogenic 
bone graft (from local and/or iliac crest bone) and/or allogenic bone 
graft. 
 

                                                                                                                         
 
 
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Number of Subjects: A total of 55 subjects will participate in the study, with up to 15 
patients recruited in this site. At least 30 patients will be enrolled in 
US sites. 
 
 Study Duration: 
The study is expected to last up to 36 months (total duration), 
including patient enrollment and a post-operative follow-up period 
of 24 months per subject.  
 
Primary Outcome 
Measures: 
 Fusion: evaluated radiographically (by AP, lateral and 
flexion/extension X-Rays) at 24 months; fusion is defined as:    
a. 
Angular motion ˂ 3º; AND  
b. Translational motion ˂ 3 mm; AND 
c. 
Presence of continuous bridging bone between the 
involved motion segment, i.e.: 
 
Presence of interbody (between endplates) 
bridging bone and absence of radiolucency > 
50%; OR 
 
Presence of left posterolateral bridging bone; 
OR 
 
Presence of left posterolateral bridging bone.  
 Pain (low back and/or leg/s): assessed based on Visual 
Analogue Scale (VAS), at 24 months; defined as an 
improvement of at least 20 mm on a 100 mm VAS from the 
baseline level. 
 Function: assessed by Oswestry Disability Index (ODI), at 24 
months; defined as an improvement of at least 15 points from 
the baseline level. 
 Safety:  
 
No worsening in neurological status (motor, sensory, 
reflex, straight leg raising, and tenderness assessments) 
and no new permanent neurological deficits present for 
at least 2 successive visits at or beyond 6 months (out 
to 24 months);  
 
Absence of device-related serious adverse events 
through 24 months; 
 
Absence of subsequent surgical interventions at the 
index level through 24 months. 

                                                                                                                         
 
 
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Secondary Outcome 
Measures: 
 Subject's Overall Well-Being: assessed by 12-Item Short 
Form Health Survey (SF-12), at 24 months; 
 Satisfaction: assessed based on VAS, at 24 months; 
 Donor Site Pain: assessed based on VAS, at 24 months; 
 Operation time; 
 Blood loss. 
 
 Follow-Up: 
Radiographic (AP, lateral and flexion/extension X-Rays) and clinical 
evaluations.  
Follow-up sessions at 6 weeks, 3 months, 6 months, 12 months, and 
24 months postoperatively, and then annually, until the last patient 
has completed 2-year follow-up.. 
 
Inclusion Criteria: 
1. Subject has degenerative disc disease (DDD) at one level, from 
L2 to S1 vertebrae, with up to Grade I spondylolisthesis.   
DDD is defined as back pain and/or radicular leg pain with 
degeneration of the disc confirmed by patient history, 
radiographic studies, and physical examination, with one or 
more of the following factors (as measured radiographically, 
either by CT, MRI or plain film, myelography, discography, 
etc.): 
 osteophyte formation of facet joints or vertebral endplates; 
 decreased disc height, on average by > 2 mm;  
 scarring/thickening of ligamentum flavum, annulus 
fibrosis, or facet joint capsule; 
 herniated nucleus pulposus; 
 facet joint degeneration/changes;  
 vacuum phenomenon. 
2. Subject is candidate for single level intervertebral fusion, with 
or without posterolateral fusion, with implantation of 
intervertebral body fusion device and supplemental fixation.  
3. Subject age is between 21 – 72 years, and subject is skeletally 
mature.  
4. Pre-operative low back and/or leg/s pain (debilitating pain that 
causes a significant disturbance of the routine daily physical 
activities) ≥ 40 mm on a 100 mm Visual Analogue Scale (VAS).   
5. Pre-operative Oswestry Disability Index (ODI) score ≥ 40 

                                                                                                                         
 
 
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percentage-point, indicating at least moderate disability 
(interpreted as moderate/severe disability). 
6. Low back and/or leg/s pain is unresponsive to prior non-surgical 
management for a minimum of six months. Non-operative 
treatment includes pain medication, physical therapy and/or 
injections.  
7. Patient must understand and sign the informed consent. 
8. Patient is willing and able to meet the proposed follow-up 
schedule including return to follow-up visits and complete 
necessary study paperwork.  
9. Patient is willing and able to follow the postoperative 
management program.   
Exclusion Criteria: 1. Previous fusion or fusion attempts, including anterior fusion or 
posterolateral fusion, at the index level. 
2. Previous fusion or fusion attempts at the adjacent levels. 
3. Prior decompression procedures that include removal of soft and 
bone tissue at the index or adjacent levels. 
4. Patient is not skeletally mature. 
5. Degenerative spondylolisthesis greater than Grade I.  
6. Spinal instability at the index level with ≥ 3 mm translation 
and/or ≥ 5 degrees angulation. Determination of instability will 
be assessed using flexion/extension lateral view radiographs. 
7. Isthmic spondylolisthesis.  
8. Radiographically confirmed moderate or severe spinal stenosis 
with associated neurogenic claudication. 
Definitions: 
 Radiographically confirmed moderate/severe stenosis is 
defined as reduction of ˃50% of central and/or foraminal 
canal diameter compared to the adjacent uninvolved 
levels.  
 Neurogenic claudication is leg, groin, or buttock pain 
and/or numbness that worsens with walking or erect 
posture and is relieved with flexion of the spine. 
9. Systemic infection or infection at the site of surgery. 
10. Metabolic bone disease, such as osteopenia, osteoporosis, and 
osteomalacia. A screening Questionnaire for osteoporosis, 

                                                                                                                         
 
 
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SCORE (Simple Calculated Osteoporosis Risk Estimation), will 
be used to screen patients who require a DEXA bone mineral 
density measurement. If DEXA is required, exclusion will be 
defined as measured T-score less than or equal to -2.5 (WHO 
definition). 
11. History of Paget’s disease or other bone pathologies, whether 
acquired or congenital, including renal osteodystrophy, 
untreated or uncontrolled hyperthyroidism, hypothyroidism, or 
hyperparathyroidism, Ehrlers-Danlos-syndrome, osteogenesis 
imperfecta, achondroplasia, tuberculosis. 
12. Personal and/or familial history NF2, and/or spinal tumor. 
13. Ankylosing spondylitis. 
14. Diffuse idiopathic skeletal hyperostosis (DISH) syndrome.  
15. Active hepatitis (viral or serum) or HIV positive, renal failure, 
systemic lupus erythematosus, or any other significant medical 
conditions which would substantially increase the risk of 
surgery. 
16. Immune deficiency disease.   
17. Patient is receiving immunosuppressive or long-term steroid 
therapy. 
18. Active malignancy or other significant medical comorbidities. 
19. All concomitant diseases that can jeopardize the functioning and 
success of the patient.  
20. Allergy to any component of the investigational device, 
including carbon fiber-reinforced polyetheretherketone (CFR-
PEEK), titanium, and tantalum. 
21. Pregnancy, or female subject interested in become pregnant 
during the duration of the study.  
22. Current chemical dependency (e.g., drug and/or alcohol abuse, 
according to DSM-V definition), as well as those with a history 
of such abuse. 
23. Uncontrolled depression, psychosis, or other symptoms of a 
mental disorder that, in the investigator’s opinion, likely would 
make the subject unable to comply with the study procedures 
and could affect the study outcome. 
24. Treatment with drugs that may interfere with bone metabolism, 
such as glucocorticosteroids, calcitonin, bisphosphonates, bone 

                                                                                                                         
 
 
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therapeutic doses of fluoride, bone therapeutic doses of vitamin 
D or vitamin D metabolites, and treatment by chemotherapy.  
25. Morbid obesity (BMI ≥ 40). 
26. Current smokers (including 3 months prior to surgery). 
27. Scoliosis, Cobb angle greater than 11°.  
28. Vertebral fractures. 
29. Severe muscular, neural or vascular diseases that endanger the 
spinal column.  
30. Missing bone structures, due to severely deformed anatomy or 
congenital anomalies, which make good anchorage of the 
implant impossible.  
31. Paralysis. 
32. Current use of other investigational drug or device. 
33. The patient is involved in a worker’s compensation case or 
spine-related litigation. 
34. The patient is a prisoner. 
 

                                                                                                                         
 
 
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3. 
INTRODUCTION 
Chronic low back pain (CLBP) occurs in up to 60% - 80% of the adult population in the 
USA, with up to 5% experiencing this pain annually 1, 2, 3. CLBP is a leading cause of 
morbidity and disability, thus constituting a leading health and economic challenge. It has 
been recognized that in some cases axial low back pain is secondary to dehydration and 
biochemical changes of the intervertebral disc. A degenerative cascade has been suggested 
by Kirkaldy-Willis 4, describing the pathophysiologic process as it affects the lumbar spine 
and individual motion segments. The term “degenerative disc disease” (DDD) has been 
coined for this entity. It should be noted, that degenerative changes may or may not be 
associated with clinical symptoms. Vast scientific reports have described degenerative 
imaging findings in asymptomatic population 5, 6. The high prevalence of the degenerative 
process in both symptomatic and asymptomatic subjects limits the ability to correlate 
anatomic derangement and clinical symptoms 7. Also, there is lack of consensus regarding 
the terminology and standardized clinical definition of DDD. 
 
Most cases of low back pain are self-limiting in that only 7% of the patients have 
symptoms that persist beyond two weeks, with only 1% of those requiring prolonged 
treatment and even fewer eventually requiring surgical intervention 8. The primary 
                                                 
1 Guo HR, Tanaka S, Halperin WE, Cameron LL. Back pain prevalence in US industry and estimates of lost 
workdays. Am J Public Health 1999; 89(7):1029-1035. 
2 Mazroa AL, Mohammad A. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and 
injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 
2012;380(9859):2163-96.  
3 Andersson GB Epidemiological features of chronic low-back pain. Andersson GB. Lancet 1999 Aug  
14;354(9178):581-585.  
4 Kirkaldy-Willis WH, Wedge JH, Yong-Hing KJR. Pathology and pathogenesis of lumbar spondylosis and  
stenosis. Spine 1978;3:319-28. 
5 Roh JS, Teng AL, Yoo JU, et al. Degenerative disorders of the lumbar and cervical spine. Orthop Clin 
North Am 2005;36:255–262. 
6 Dickerman RD, Zigler JE. Discogenic back pain. In: Spivak JM, Connolly PJ, eds. Orthopaedic Knowledge 
Update Spine 3. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2006:319–329. 
7 Modic MT, Ross JS. Lumbar degenerative disk disease. Radiology 2007; 245: 43-61. 
8 Report of the Quebec Task Force on Spinal Disorders. Scientific approach to the assessment and 
management of activity-related spinal disorders. A monograph for clinicians. Spine 1987 Sep;12 

                                                                                                                         
 
 
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treatment for the majority of patients with DDD is non-operative. A wide variety of non-
operative treatments are available including physical therapy (both active and passive 
modalities), medications (including analgesics, anti-inflammatories, muscle relaxants, and 
antidepressants), injections (both epidural and facet injections), patient education, 
chiropractic manipulation, traction, bracing, and acupuncture. However, if symptoms 
persist and/or progress despite non-operative management (particularly to the point of 
significantly impacting quality of life and the ability of the patient to function), surgery 
becomes an option. It has been recognized that surgery has favorable outcome for selected 
population that has failed non-operative treatment.  
 
The current surgical standard of care for treating lumbar degenerative disease includes 
interbody fusion (ALIF, PLIF, TLIF), combined with posterolateral arthrodesis and pedicle 
screw systems fixation 
9. Over the last few decades, posterior pedicle screws 
instrumentation have evolved and revolutionized surgical care of various spinal disorders. 
Presently, pedicle screw systems are the workhorse of spinal instrumentation for the adult 
spine. Since their introduction in 1969, numerous advances in surgical and instrumentation 
techniques have been adopted, leading to continues progress in clinical outcomes 10.  
 
The evolution of biomaterials assigned for these systems contributed to this progress. 
Titanium has gained wide popularity and has largely replaced conventional stainless steel. 
However, metallic implants possess several inherent shortcomings, including that metal 
alloys may severely degrade the quality of images of modern imaging techniques (CT and 
                                                                                                                                                    
(7Suppl):S1-59. 
9  Zigler JE, Delamarter RB. Does 360° lumbar spinal fusion improve long-term clinical outcomes after 
failure of conservative treatment in patients with functionally disabling single-level degenerative lumbar 
disc disease? Results of 5-year follow-up in 75 postoperative patients. Int J Spine Surg. 2013 Dec 1;7:e1-
7. 
10  Gaines RW Jr. The use of pedicle-screw internal fixation for the operative treatment of spinal disorders. J 
Bone Joint Surg Am. 2000 Oct;82-A(10):1458-76. 
 

                                                                                                                         
 
 
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MRI) due to metal-induced artifacts, and therefore may prevent accurate postoperative 
assessment of region of interest near the implants 11, 12, 13. 
Carbon fiber-reinforced-polyetheretherketone composite (CFR-PEEK) has been suggested 
to overcome these limitations. The potential advantages of this composite material include 
inherent radiolucency and MRI and CT compatibility, resulting in negligible implant-
induced artifacts, and superior fatigue life in compared to traditional implants. In addition, 
CFR-PEEK composites are biocompatible, and are rigid with structural stiffness equivalent 
to metallic biomaterials. All of those properties are ideal for spinal surgical implants. CFR-
PEEK based spinal cages and other CFR-PEEK bone implants are cleared and in clinical 
use, and multiple studies reported their safety and effectiveness 14, 15.  
 
The aim of the current study is to evaluate the safety and effectiveness of a novel CRF-
PEEK pedicle screw system, the CarboClear Pedicle Screw System ("CarboClear System"). 
This is a rigid, pedicle screw system, intended to provide immediate immobilization and 
stabilization of the lumbar and/or sacral spine in DDD patients undergoing spinal fusion. 
The CarboClear System comprises polyaxial pedicle screws, longitudinal rods, and locking 
elements. The implants are made of CFR-PEEK with radiopaque markers. The threaded 
portion of the pedicle screws is encased within a thin titanium shell. The design and 
dimensions of the implant components are similar to those of other, market-available 
pedicle screw systems. The implantation technique and the instrumentation used during the 
operation are also similar to those used for other, cleared, pedicle screw systems. 
                                                 
11 Rutherford EE, Tarplett LJ, Davies EM, Harley JM, King LJ, Lumbar spine fusion and stabilization: 
hardware, techniques, and imaging appearances. Radiographics, 2007;27(6):1737-1749. 
12 Romero-Muñoz LM, Alfonso M, Villas C, Zubieta JL, Effect of brightness in the evaluation of lumbar 
pedicular screws position: clinical study. Musculoskeletal Surgery, 2013;97(2): 159-164. 
13  Stradiotti P, Curti A, Castellazzi G,  Zerbi A, Metal-related artifacts in instrumented spine. Techniques for 
reducing artifacts in CT and MRI: state of the art. Eur Spine J, 2009;18(1):102–108. 
14  Kurtz SM, Devine JN. PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 2007 
Nov;28(32):4845-69. Epub 2007 Aug 7. 
15  Vannabouathong C, Sprague S, Bhandari M, Li CS. The Use of Carbon-Fiber-Reinforced (CFR) PEEK 
Material in Orthopedic Implants: A Systematic Review. Clin Med Insights Arthritis Musculoskelet Disord. 
2015 Feb 23;8:33-45. 

                                                                                                                         
 
 
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Pre-clinical testing indicates that biomechanical performance of the system is similar to that 
of titanium pedicle screw systems. In addition, the system is being clinically investigated 
outside the USA, with good interim results. 
 
This study is designed to demonstrate the safety and effectiveness of the CarboClear 
System for lumbar/sacral fusion requiring immediate, rigid stabilization of the spine. 

                                                                                                                         
 
 
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4. 
DEVICE DESCRIPTION 
4.1 
DEVICE INTENDED USE/INDICATIONS FOR USE 
The CarboClear Pedicle Screw System is intended to provide rigid immobilization and 
stabilization of lumbar and/or sacral segments as an adjunct to fusion in patients with 
degenerative disc disease (DDD) at one level from L2 to S1, with up to Grade I 
spondylolisthesis. DDD is defined as back pain of discogenic origin with degeneration of 
the disc confirmed by history and radiographic studies. Patients should be skeletally mature 
and have at least six months of non-operative treatment. 
The CarboClear Pedicle Screw System is designed for use with intervertebral body fusion 
device and with autogenous and/or allogenic bone graft comprised of cancellous and/or 
corticocancellous bone graft.  
 
4.2 
SYSTEM DESCRIPTION 
The CarboClear Pedicle Screw System ("CarboClear System") is composed of implants in 
various dimensions, used to build a spinal construct; and of a set of surgical instruments, 
intended to assist in the insertion and placement of the implants. Each of these components 
is described below. 
 
4.2.1 
IMPLANT DESCRIPTION 
CarboClear System comprises polyaxial pedicle screws, longitudinal rods, and locking 
elements. 
The implants are made of carbon fiber-reinforced polyetheretherketone (CFR-PEEK) with 
radiopaque markers. The threaded portion of the pedicle screws is encased within a thin 
titanium shell.  
 

                                                                                                                         
 
 
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4.2.1.1 
Polyaxial Pedicle Screws 
The polyaxial pedicle screws comprise a spherical head enclosed within a housing ("tulip"), 
enabling screw positing in a variety of angles and facilitating connection of the rod. Both 
cannulated and non-cannulated screws are available. The cannulated screws include a 
lumen of 1.3 mm diameter, to enable their insertion into the bone over a guide wire.  
The screws are made of CFR-PEEK, and their threaded portion as well distal tip are 
encased within a 0.1 mm thickness shell, made of pure titanium (Grade I or II, per ASTM F 
67), so that the screw portion that contacts the bone is made of titanium. The titanium shell 
is a sealed, non-porous, coating. It enables screw visualization under imaging, during screw 
introduction into the vertebra, as well as post-operatively. As the metal content in the screw 
is minimal, the metal-induced artifacts seen in CT/MRI imaging are minimal compared to 
all-metal pedicle screw systems.   
The Pedicle Screw is depicted in Figure 1. Each pedicle screw is provided to the user as a 
"pedicle screw assembly", together with a tulip-like component that surrounds the screw 
spherical head (refer also to Figure 2 below). The tulip, made of CFR-PEEK, includes a 
tantalum wire along its perimeter, to allow its visualization under imaging. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 1: CarboClear System - Pedicle Screw 
Threaded 
Portion  
(Encased within 
Titanium Shell) 
Spherical Head  
(within Tulip) 
 
Tantalum 
 Marker   

                                                                                                                         
 
 
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The pedicle screws are available in diameter of 5.5 mm, 6.5 mm and 7.5 mm, in lengths 
ranging from 35 mm to 55 mm (depending on screw diameter), in 5 mm increments.  
 
 
   
  
 
 
 
 
 
 
 
 
4.2.1.2 
Rods 
Longitudinal rods, of 6.0 mm diameter, available in lengths ranging from 30 mm to 220 
mm. The rods are provided pre-cut, either straight or pre-contoured. The curved rods are 
provided with the following optional curvature radii: light curve - radius of 440 mm; 
moderate curve - radius of 240 mm; and prominent curve - radius of 120 mm).  
A tantalum wire is incorporated along the long axis of the CRF-PEEK rods, thus enabling 
their visualization under imaging. 
The curved and straight rods are depicted in Figure 3.  
 
 
 
 
 
 
 
Figure 3: CarboClear System – Curved (Left) and Straight (Right) Rods 
Figure 2: CarboClear System - Pedicle Screw Assembly 
 
Screw Tulip 
Screw Thread 

                                                                                                                         
 
 
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4.2.1.3 
Locking Element  
The component is made of CRF-PEEK and comprises a tantalum marker, to provide for its 
visualization under imaging.  
At its upper portion, the locking element includes a lumen to accommodate the rod. During 
operation, the lower portion of the locking element is positioned within the cavity of the 
screw tulip, above the screw spherical head. In order to lock the implant components, the 
lower portion of the locking element is pressed against the tulip using dedicated 
instrumentation.  
 
 
    
 
 
 
 
 
 
 
 
 
 
Prior to final locking, the physician may slide the locking elements along the rod, to locate 
them at a desired position, and afterwards to lock them at that position. The locking 
elements may be provided already mounted over the rod, as depicted in Figure 5.  
 
 
Figure 4: CarboClear System – Locking Element 
 
Opening for the Rod 

                                                                                                                         
 
 
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4.2.1.4 
Implant Assembly 
Once assembled and locked, the CarboClear implant provides for a rigid construct, with no 
relative motion between its components. The construct (Figure 6 (standalone) and Figure 7 
(attached to a spinal model)) provides for immediate stabilization and immobilization of the 
involved spinal segment.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 6: CarboClear System – Assembly of Implant Components 
Figure 5: CarboClear System – Locking Elements Mounted on a Straight Rod (Right);  
and on a Curved Rod (Left) 
 
Locking Element 
Rod 

                                                                                                                         
 
 
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Table 1 summarizes the suggested implant components of the CarboClear System and their 
characteristics (materials and dimensions). Implant dimensions are within the range of 
dimensions seen in similar pedicle screw systems available on the market.  
 
 
 
Figure 7: CarboClear System – Assembly of Implant Components, Attached to A Spinal Model 

                                                                                                                         
 
 
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Table 1: CarboClear System – Implant Components 
Implant 
Component 
Material 
Thread Diameter  
[mm] 
Length 
[mm] 
ROM 
[Degrees] 
Polyaxial Pedicle 
Screw  
CFR-PEEK;  
Screw shank - CP Ti shell; 
Tulip includes a Ta wire 
 
 5.5 * 
35, 40, 45  
40 
6.5 ** 
35, 40, 45, 50 
30 
7.5 ** 
35, 40, 45, 50, 55  
20 
Rod  
Straight 
CFR-PEEK, with Ta wire 
6.0 
30 – 120 
(5 mm steps) 
- 
Rod  
Curved (Moderate) / 
Curved (Prominent) 
30 – 80 
(5 mm steps); 
90 – 200 
(10 mm steps) 
- 
Rod  
Curved (Light) 
30 - 220 
(10 mm steps) 
- 
Locking Element 
CFR-PEEK, with Ta marker 
- 
- 
- 
*   Provided non-cannulated 
** Provided either cannulated or non-cannulated 
 
4.2.2 
SURGICAL INSTRUMENTS 
The instrumentation to be provided with CarboClear System is used for bone preparation 
and implant introduction and placement (as well as for implant removal, if required). 
The instruments are, in general, multi-use surgical instruments, made of metal (such as 
stainless steel complying with ASTM F 899 or ASTM F 138) and polymeric material (e.g., 
PEEK and propylux). They are similar to instruments used with other market-available 
pedicle screw systems, and to instruments supplied with other systems by the Company. 
Some accessories, such as guide wires, may be provided for single use.  
 
The instrumentation for the CarboClear System includes the following components: 
Pedicle Awl  
Used to gain access through the bone cortex 
into the pedicle.  

                                                                                                                         
 
 
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Pedicle Probes  
Straight and curved, pointed or blunt, pedicle 
probes, intended to tunnel through the pedicle 
cancellous bone into the vertebral body.  
The probes include depth markings, to 
facilitate the assessment of pedicle screw 
appropriate length.  
 
Pedicle Feeler  
A ball-tipped device, used to verify pedicle 
wall integrity prior to tapping. It is marked to 
assist in the assessment of pedicle screw 
length. 
 
1.5 mm Guide Wire  
A ball-tipped guide wire. May be used to 
maintain trajectory during tapping and 
reaming. 
 
1.1 mm Guide Wire  
May be used to maintain trajectory for the 
insertion of the cannulated pedicle screw. 
 
Bone Taps  
Cannulated taps, with diameter range of 4.5 - 
7.5 mm. Used with a dedicated handle, to 
prepare the pedicle screw canal. May be used 
over the guide wire. The taps are marked to 
 
 
 
 
 
 

                                                                                                                         
 
 
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assist in the assessment of pedicle screw 
length.  
 
Pedicle Surface Reamer  
May be used, if required, to ream the surface 
of 
the 
pedicle 
in 
order 
to 
allow 
accommodation of the pedicle screw head and 
tulip. The reamer is cannulated to enable 
reaming over the guide wire. 
 
X-Ray Markers 
May be used for radiographic verification of 
pathway positioning. Available in notched or 
smooth options, to distinguish right or left 
placement and to assess screw length.  
The markers are used with a dedicated 
inserter. 
 
Pedicle Screw Screwdriver  
A dedicated screwdriver, intended for the 
insertion of the pedicle screw into the pedicle. 
It is cannulated and may be used over the 
guide wire.  
 
Tulip Adjusters  
Used in case adjusting of the tulip orientation 
is required. 
 
 
 
X-Ray Marker, Left 
X-Ray Marker, Right 
 
 

                                                                                                                         
 
 
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Rod Measuring Templates  
Straight and curved bendable rods, in several 
lengths, used to aid in selecting the proper 
rod. May be used with the Rod Holding 
Forceps. 
 
Rod Holding Forceps (& X-Ray Marker 
Inserter)  
May be used to securely hold the rod for its 
placement and positioning within the implant 
construct.  
 
Rod & Locking Elements Holder  
Used to securely hold the locking elements 
and the rod, for their placement and 
positioning within the implant construct. 
 
Rod Pusher  
Used to push the rod for its location in place, 
if required.  
  
Distractor 
Used to perform distraction, in case required.  
 
Persuader  
The persuader may be used for partial 
locking.  
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
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Locking Device 
Used to press the locking element against the 
screw's tulip, in order to lock the screw-rod 
construct at a desired angle.  
 
Disassembly Device  
Used to open (disconnect) the locked rod-
screw construct, in case re-positing or 
removal of the implant is required.  
The unlocker component is connected to the 
distal end of the Locking Device.  
 
Pedicle Screw Extractor (for damaged 
screw) 
The screw extractor, assembled to the T-
handle, may be used in case removal of a 
damaged (e.g., broken) pedicle screw is 
required. The handle should be counter-
clockwise rotated, to remove the pedicle 
screw. The extractor is available in three 
dimensions, to comply with the different 
diameters of the pedicle screw. 
 
Additional surgical instruments, such as mallet may also be provided, to assist in the 
procedure, when required. 
 
Unlocker  
Component 
 
Pedicle Screw 
Rod 

                                                                                                                         
 
 
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4.2.3 
PRINCIPLES OF OPERATION 
The implant components of the CarboClear System are implanted in a similar manner to 
that used for the implantation of other pedicle screws systems available on the market, as 
an adjunct to vertebrae fusion procedure.  
 
A detailed operational procedure is described in the Surgical Technique (Appendix A).  
In short, the implants of the CarboClear System are introduced in a standard approach. 
Following preparation of the vertebral pedicles, the screws are inserted into the vertebral 
body via the pedicles. A rod with two or more locking elements is then placed at each side 
over adjacent screws, to longitudinally connect them. The locking elements may slide along 
the rod, to be located at a desired position. Initial (partial) locking is conducted by pressing 
the locking element against the screw' tulip. At this stage, distraction may be performed, if 
required. Following confirmation of implant components position, a final, firm locking of 
the rod to the screws is performed using the locking device.   
 
 
 

                                                                                                                         
 
 
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5. 
INVESTIGATIONAL PLAN 
5.1      PURPOSE 
The purpose of this clinical investigation is to demonstrate the safety and effectiveness of 
the CarboClear Pedicle Screw System ("CarboClear System"), for skeletally mature DDD 
patients undergoing one level spinal fusion, in combination with interbody fusion device, 
and requiring immediate, rigid, posterior spinal stabilization of the lumbar and/or sacral 
spine.  
  
5.1.1   OUTCOME MEASURES  
The following outcome measures will be evaluated in subjects participating in the study: 
Primary Effectiveness and Safety Outcome Measures:   
 
Fusion: evaluated radiographically (by AP, lateral and flexion/extension X-Rays) at 
24 months; fusion is defined as:    
a. 
Angular motion ˂ 3º 16; AND  
b. Translational motion ˂ 3 mm; AND 
c. 
Presence of continuous bridging bone between the involved motion 
segment 17, i.e.: 
 
Presence of interbody (between endplates) bridging bone and 
absence of radiolucency > 50%; OR 
 
Presence of left posterolateral 18 bridging bone; OR 
 
Presence of left posterolateral 18 bridging bone.  
                                                 
16  In addition to angular motion of 3 degrees, the Company will provide fusion data and analysis using a 
threshold of 5° of angular motion. Additional information is provided in Section 3.10.1.  
17  The definition above calls for “continuous” bridging bone (with or without trabeculation). That is, solid 
bridging with no intervening fractures or discontinuities. Conventional plain film imaging rarely supports 
visualization of trabeculae. 
18  Right posterolateral - between the right facets, pedicle and/or transverse processes; left posterolateral - 
between the left facets, pedicle and/or transverse processes. 

                                                                                                                         
 
 
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 
Pain (low back and/or leg/s): assessed based on Visual Analogue Scale (VAS), at 
24 months; defined as an improvement of at least 20 mm on a 100 mm VAS from 
the baseline level. 
 
Function: assessed by Oswestry Disability Index (ODI), at 24 months; defined as 
an improvement of at least 15 points from the baseline level. 
 
Safety:  
 No worsening in neurological status (motor, sensory, reflex, straight leg 
raising, and tenderness assessments) and no new permanent neurological 
deficits present for at least 2 successive visits at or beyond 6 months (out to 
24 months); 
 Absence of device-related serious adverse events through 24 months. 
 Absence of subsequent surgical interventions at the index level through 24 
months. 
  
Secondary Outcome Measures:   
 
Subject's Overall Well-Being: assessed by 12-Item Short Form Health Survey (SF-
12), at 24 months; 
 
Satisfaction: assessed based on VAS, at 24 months; 
 
Donor Site Pain: assessed based on VAS, at 24 months; 
 
Operation time; 
 
Blood loss. 
 
5.2      STUDY DESIGN 
A prospective, multi-center, confirmatory, single arm, study.  
A total of up to 55 subjects with DDD at one level from L2 to S1, who have failed to 
improve with conservative treatment for at least six months prior to enrollment, will 
participate in this study. At least 30 patients will be enrolled at US sites with the rest being 
enrolled in sites outside the US. 
 

                                                                                                                         
 
 
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All patients will be implanted with the investigational device and an FDA cleared PEEK 
interbody fusion device (Medtronic's Capstone PEEK Spinal System (K073291, K103731, 
and more); or Medtronic's Crescent PEEK Spinal System (K094025, K133216, and more)), 
using PLIF or TLIF approach, and undergo interbody spinal fusion. According to the 
physician discretion, posterolateral spinal fusion may also be performed, using autogenic 
bone graft (from local and/or iliac crest bone) and/or allogenic bone graft comprised of 
cancellous and/or corticocancellous bone graft. As Medtronic's Capstone and Crescent 
Systems are cleared only with autogenous bone graft, only autogenous bone graft will be 
packed into the cage. In case posterolateral fusion is also conducted, either autogenous 
bone graft or allogenic bone graft, as detailed above, may be used at this location.  
 
Pre-clinical data (bench testing), as described in the Investigator Brochure, demonstrated 
equivalency to cleared, rigid, metal, pedicle screw systems with similar intended use, both 
in terms of test results values and tests failure modes. In addition, clinical data regarding 
the use of the subject device, which is currently available from an on-going, out-of-the-US 
(OUS), multi-center study, and is summarized in the Investigator Brochure, also supports 
the effective and safe use of the investigational device. The discussed confirmatory clinical 
study is designed to further support the safety and effectiveness of the CarboClear System.  
 
The results of the suggested study will be evaluated in relation to historical-based data, 
derived from the literature and described in Section 5.2.1.  
Comparison to retrospective data from the literature regarding metal pedicle screw systems 
used in conjunction with interbody fusion device will be made in terms of efficacy and 
safety.  
Individual patient success (i.e., overall success) is defined as a composite endpoint. A 
patient will be considered a "success" if all primary effectiveness and safety outcome 
measures listed above are met. As detailed later in this document, the statistical analyses of 
the suggested study will be descriptive in nature. 
 

                                                                                                                         
 
 
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During the clinical investigation, the patients will be evaluated preoperatively (baseline), 
intraoperatively, at discharge, and postoperatively at 6 weeks, 3 months, 6 months, 12 
months and 24 months, and then annually, until the last patient completed 2-year follow-up. 
Radiographic endpoints will be evaluated by two independent reviewers at an imaging core 
laboratory (Medical Metrics, Inc., Texas). In the case of a disagreement between the two 
radiographic assessors, a third independent reviewer will evaluate the radiographic images 
to adjudicate the findings. In addition, a CT scan will be acquired for subjects in which 
bridging bone status could not be determined form X-Rays, at each time point starting at 6 
months post-operatively. 
 
At each evaluation time point, as applicable, the primary and secondary endpoints shall be 
evaluated (e.g., pain and function evaluations based on patient questionnaires shall be 
performed pre-operatively and starting at 6-week follow-up visit; fusion assessment will be 
made starting at 6-month). Complications and adverse events will be evaluated at each 
follow-up visits and over the course of the clinical trial. Detailed evaluation schedule is 
provided in Table 8. 
 
5.2.1   LITERATURE CONTROL 
In order to identify studies for the literature control, a poly-phasic approach was used: 
First, Table 6 of the FDA Executive Summary, Prepared for the May 22, 2013 Meeting of 
the Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory 
Committee, 2013 – Classification Discussion, Pedicle Screw Spinal Systems (Certain Uses 
– Class III Indications for Use) ("FDA Executive Summary") was used for extracting 
articles believed to have valid scientific evidence. 
The FDA Executive Summary was reviewed. This document includes a survey of literature 
aimed at establishing the safety and effectiveness of pedicle fixation systems as an adjunct 
to lumbar fusion for treatment of DDD patients. Table 6 of the said document 
(“Effectiveness Data for Posterior Pedicle Screw Spinal Systems for Class III Degenerative 
Indications”) outlines key manuscripts identified by the Agency. All manuscripts reported 

                                                                                                                         
 
 
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in that table were extracted and carefully reviewed. Of these, prospective studies which 
focused on circumferential lumbar fusion and pedicle screw fixation or posterolateral 
fusion with pedicle screw fixation for DDD patients, and which provide, at a minimum, 
fusion definition and fusion rate results, were selected for the review. Thus, retrospective 
studies presented in Table 6 (e.g., Acosta, Barnes and Al-Masry), and studies that did not 
report fusion definition and/or fusion results (e.g., Glassman), were excluded. Where 
applicable, both arms of randomized studies were captured for the literature control. 
Next, a computerized search of the National Library of Medicine MEDLINE database 
utilizing the online search engine PubMed 19 was carried out, to cross-reference these 
results. 
The first search was carried out during November-December 2014, and was 
complemented by a second search during April-May 2015. 
The following search terms were utilized: "fusion" [Title/Abstract], OR “arthrodesis” 
[Title/Abstract], OR “Interbody” [Title/Abstract], OR "Posterolateral" [Title/Abstract];  
AND "lumbar" [Title/Abstract], OR "lumbosacral" [Title/Abstract]; AND “degenerative 
disc disease” [Title/Abstract], OR “disc degeneration” [Title/Abstract], OR "DDD" 
[Title/Abstract], OR "spondylosis" [Title/Abstract], OR “back pain” [Title/Abstract]. 
The searches were limited to articles published in "English" [Language], “Humans” 
[Medical Subject Headings], NOT “case report” [Title], NOT "cadaver" [Title] OR 
"anatomical" [Title], NOT "children" [Title] OR "adolescent" [Title], NOT kinematic 
[Title/Abstract] OR “finite element” [Title/Abstract], from April 1997 to 2015.  
A total of 3,990 reports were obtained. 
 
Eleven eligible studies were selected for the analysis, according to the following criteria:  
(1) subjects were skeletally matured and had undergone spinal fusion for the lumbar 
and/or sacral spine;  
(2) the intervention included instrumented fusion (interbody and/or posterolateral 
fusion), in at least one arm of the study;  
                                                 
19 http://www.ncbi.nlm.nih.gov/pubmed 

                                                                                                                         
 
 
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(3) indications were DDD with or without degenerative spondylolisthesis (up to Grade 
I);  
(4) the study reported at least fusion definition and results of fusion rate;  
(5) patients were followed up to at least one year after surgery; 
(6) number of patients was at least 20; 
(7) manuscripts were given priority if published in high ranking journals and quoted in 
meta-analysis. 
(8) high level of evidence manuscripts (I and II levels). 
The flowing manuscripts were selected: 
1. Fritzell P, Ha¨gg O, Wessberg P, Nordwall A, and the Swedish Lumbar Spine Study 
Group. Chronic Low Back Pain and Fusion: A Comparison of Three Surgical 
Techniques. A Prospective Multicenter Randomized Study from the Swedish 
Lumbar Spine Study Group. Spine 2002;27(11):1131–1141. 
2. Zigler J, Delamarter R, Spivak JM, Linovitz RJ, Danielson GO, Haider TT, 
Cammisa F, Zuchermann J, Balderston R, Kitchel S, Foley K, Watkins R, Bradford 
D, Yue J, Yuan H, Herkowitz H, Geiger D, Bendo J, Peppers T, Sachs B, Girardi F, 
Kropf M, Goldstein J. Results of the prospective, randomized, multicenter Food and 
Drug Administration investigational device exemption study of the ProDisc-L total 
disc replacement versus circumferential fusion for the treatment of 1-level 
degenerative disc disease. Spine (Phila. Pa 1976) 2007;32:1155-1162. 
3. Anjarwalla NK, Morcom RK, Fraser RD. Supplementary stabilization with anterior 
lumbar intervertebral fusion--a radiologic review. Spine (Phila. Pa 1976) 
2006;31:1281-1287. 
4. Christensen FB, Hansen ES, Eiskjær SP, Høy K, Helmig P, Neumann P, 
Niedermann B, Bu¨nger CE. Circumferential Lumbar Spinal Fusion with Brantigan 
Cage 
versus 
Posterolateral 
Fusion 
with 
Titanium 
Cotrel–Dubousset 
Instrumentation. A Prospective, Randomized Clinical Study of 146 Patients. Spine 
2002;2(23):2674–2683. 

                                                                                                                         
 
 
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5. Brantigan JW, Steffee AD, Lewis ML, Quinn LM, Persenaire JM. Lumbar 
interbody fusion using the Brantigan I/F cage for posterior lumbar interbody fusion 
and the variable pedicle screw placement system: two-year results from a Food and 
Drug Administration investigational device exemption clinical trial. Spine (Phila. Pa 
1976) 2000;25:1437-1446. 
6. Hackenberg L, Halm H, Bullmann V, Vieth V, Schneider M, Liljenqvist U. 
Transforaminal lumbar interbody fusion: a safe technique with satisfactory three to 
five year results. Eur. Spine J 2005;14:551-558. 
7. Brox JI, Sorensen R, Friis A, Nygaard O, Indahl A, Keller A, Ingebrigtsen T, 
Eriksen HR, Holm I, Koller AK, Riise R, Reikeras O. Randomized Clinical Trial of 
Lumbar Instrumented Fusion and Cognitive Intervention and Exercises in Patients 
with Chronic Low Back Pain and Disc Degeneration. Spine 2003;28:1913-1921. 
8. Delamarter R, Zigler JE, Balderston RA, Cammisa FP, Goldstein JA, Spivak JM. 
Prospective, randomized, multicenter Food and Drug Administration investigational 
device exemption study of the ProDisc-L total disc replacement compared with 
circumferential arthrodesis for the treatment of two-level lumbar degenerative disc 
disease: results at twenty-four months. J Bone Joint Surg. Am. 2011;93:705-715. 
9. Christensen FB, Hansen ES, Laursen L, Thomsen K, Bu¨nger CE. Long-Term 
Functional Outcome of Pedicle Screw Instrumentation as a Support for 
Posterolateral Spinal Fusion Randomized Clinical Study With a 5-Year Follow-up 
Spine 2002;27(12):1269–1277. 
10. Narayan P, Haid RW, Subach BR, Comey CH, Rodts GE. Effect of spinal disease 
on successful arthrodesis in lumbar pedicle screw fixation. J Neurosurg Spine 
2002;97:277–280. 
11. Arnold PM, Robbins S, Paullus W, Faust S, Holt R, McGuire R. Clinical outcomes 
of lumbar degenerative disc disease treated with posterior lumbar interbody fusion 
allograft spacer: a prospective, multicenter trial with 2-year follow-up. Am. J 
Orthop. (Belle Mead NJ.) 2009;38, E115-E122. 
  

                                                                                                                         
 
 
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Data from the studies was extracted from full text articles and is summarized in the tables 
presented in Appendix B, in accordance with the requirements of the "FDA Guidance 
Document for the Preparation of IDEs for Spinal Systems; issued on January 13, 2000".   
It is noted, that where an article describes a randomized clinical trial (RCT), only the study 
arm/s regarding circumferential fusion and pedicle screw and/or posterolateral fusion with 
pedicle screw was taken for the following analysis. 
Please note, that in order to prevent misinterpretation, whenever possible the text in the 
fields of the tables in Appendix B was copied from the articles, to use the exact wording 
used by the authors.  
 
The following paragraphs display the results regarding fusion rate, pain (VAS), function 
(ODI), and safety (adverse events), as presented in the literature control manuscripts (and in 
the FDA Executive Summary). 
 
A. 
Fusion 
The following table summarizes the fusion rates, as described in ten of the 11 articles 
referenced above. One study (Arnold) was not included in the fusion analysis due to 
discrepancies in fusion rates reported in the article. Please see detailed explanation in 
Appendix B, page 65.  
 
A total of ten level I and II studies (556 patients) reported radiographic fusion outcome for 
DDD patients who underwent circumferential lumbar arthrodesis with pedicle screws, or 
posterolateral fusion with pedicle screws, and are used as historical controls.  
Nine of those ten studies reported fusion outcome for homogenous cohorts or sub-cohorts 
(i.e., stratified for DDD patients) using x-ray methods and are therefore analogous to the 
subject IDE.  
In four studies (Brantigan, Christensen, Christensen II and Brox), subgroup stratification 
for single- and double level was not provided for fusion outcome parameter. One study 
(Delamarter) report fusion rates for two level surgery DDD cohort. 

                                                                                                                         
 
 
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In one study (Hackenberg), the results refer to a mixed cohort (DDD and isthmic 
spondylolisthesis). Nevertheless, most of the patients were DDD patients, and as the non-
stratified fusion rate is similar to studies evaluating only DDD patients, it is believed the 
results of these studies are appropriate to be included in the control group as well. 
Therefore, this study can also be included when determining the control fusion rate. 
Several of the studies evaluated fusion using tools and definitions less rigorous than those 
suggested for the proposed IDE study (e.g., without flexion-extension radiographs, and thus 
with no motion assessment). Therefore, the reported fusion rates of those articles may be 
regarded as worst case for the purpose of comparison. On the other hand, one study 
(Anjarwalla) used thin cut CT to evaluate fusion, which is expected to yield a slightly 
lower fusion rate. Although the proposed study uses radiographs to assess fusion, both 
studies use x-rays to assess fusion. Therefore, the slight difference in imaging modalities 
does not preclude using the results of the study when determining the control fusion rate.  
Please note, that the ten studies utilized autogenous bone graft (mainly iliac crest bone 
graft), which is associated with higher fusion rates than allograft.  
Overall, the compilation of these ten articles, reporting fusion results for a total of 556 
DDD patients, provides for reliable control group for comparison of fusion rate. It is 
emphasized that all of the mentioned studies were regarded as appropriate for the review of 
DDD patients in the FDA Executive Summary, and thus are reported in Table 6 of the said 
document.   
Seven of the ten studies report fusion rates at two years, while two studies (Christensen and 
Nrayan) reports rates at one year. One study (Christensen II) reports fusion rate at both one 
and two years. Slightly higher fusion rates are expected at two years as compared to one 
year. As the fusion rate of the subject device is assessed at one year, it is either analogous 
or worst-case compared to the literature control. Therefore, despite differences in time 
points, a valid comparison can be made. 
Fusion success rates reported in the ten manuscripts, and calculated weighted average of 
values, are presented in the tables below. The weighting factor is the number of patients in 
each study. 

                                                                                                                         
 
 
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Table 2: Literature Control - Radiographic Fusion Outcome 
*  Results refer to several diagnoses. In addition, subgroup stratification for single- and double level (or more) is not provided for 
fusion outcome parameter. 
‡    Subgroup stratification for single- and double level (or more) is not provided for fusion outcome parameter. 
☼  The number of DDD patients available for radiographic evaluation is assumed to be 22. The authors report the number of operated 
patients (73) and their stratification to the following 3 sub-groups: 24 with primary degeneration; 25 with secondary 
degeneration; and 24 with isthmic spondylolisthesis. Of these 73 patients, radiographic evaluation was performed for 67 patients 
(no stratifications to the 3 sub-groups). As the number of patients in each of the 3 sub-groups is similar, we arbitrary decided that 
2 patients in each group were not available for the radiographic evaluation. 
♦   The number of DDD patients available for radiographic evaluation is assumed to be 22. The authors report the number of operated 
patients (72) and their stratification to the following 3 sub-groups: 19 with primary degeneration; 27 with secondary 
degeneration; and 27 with isthmic spondylolisthesis. Of these 72 patients, radiographic evaluation was performed for 57 patients 
(no stratifications to the 3 sub-groups). As the number of patients in each of the 3 sub-groups is similar, we arbitrary decided that 
5 patients in each group were not available for the radiographic evaluation. 
§     Per CT.  
♣    According to FDA Summary of Safety and effectiveness.  
As shown in the table, the fusion rates reported in the literature control range from 77% to 
97%. 
 
 
 
Single Level 
 Double Level 
Procedure 
Diagnosis 
Cohort Size 
Fusion 
Nfused/Nchhort 
Fusion 
Rate [%] 
Fritzell 
2002 (Arm I) 
N24=43 
N24=21 
ALIF or PLIF 
+ PLF + PSS 
DDD 
N24=64 
58 
64 
91 
2 years 
Fritzell 
2002 (Arm II) 
N24=35 
N24=27 
PSF + PSS 
DDD 
N24=62 
54 
62 
87 
2 years 
Zigler 
2007 
N24=69 
- 
ALIF + PLF  
+ PSS 
DDD 
N24=69 
67 
69 
97 
2 years 
Anjarwalla 
2006 
N24=14 
N24=10 
ALIF + PLF  
+ PSS 
DDD 
N24=24 
21 
24 
88 § 
2 years 
Christensen ‡ 
2002 (Arm I) 
Cohort comprised 1-2 level 
surgeries; data not stratified 
ALIF + PLF  
+ PSS or facet 
joints screws 
DDD 
N12=22 
(only DDD  
patients) ☼ 
19 
22 
86 
1 year 
Christensen ‡  
2002 (Arm II) 
Cohort comprised 1-2 level 
surgeries; data not stratified 
PLF + PSS 
DDD 
N12=22 
(only DDD  
patients ) ♦ 
19 
22 
86 
1 year 
Brantigan ‡ 
2000 
Cohort comprised 1-3 level 
surgeries; data not stratified 
PLIF + PLF  
+ PSS 
DDD 
N24=91 
82 
91 
90 ♣ 
2 years 
Hackenberg *   
2005 
N36=39 
N36=11 (2-level) 
N36=2 (3-level) 
TLIF + PLF  
+ PSS 
30 DDD +  
22 isthmic  
spondyloli-
sthesis 
N36=52 
 
46 
52 
89 
2 years 
Brox ‡  
2003 
Cohort comprised 1-2 level 
surgeries; data not stratified 
PLF + PSS 
DDD 
N12=35 
29 
35 
84 
2 years 
Delamarter  
2009 
- 
N24=61 
ALIF + PLF  
+ PSS 
DDD 
N24=61 
47 
61 
77 
2 years 
Christensen II ‡  
2002 
Cohort comprised 1-2 level 
surgeries; data not stratified 
PLF + PSS 
DDD 
N=20 
15 
20 
77 
1 year 
Naryan  
1997 
N
12
=
34
 
- 
PLF + PSS 
DDD 
N12=34 
31 
34 
91 
1 year 

                                                                                                                         
 
 
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The following sections provide for calculation for the control group fusion rates. 
For dichotomy (binary) outcome parameters, the following formulas were used to compute 
weighed average and standard deviation:  
 
𝑊𝑒𝑖𝑔ℎ𝑡𝑒𝑑 𝑎𝑣𝑒𝑟𝑎𝑔𝑒= 𝑛1𝑝1 + 𝑛2𝑝2 … 𝑛𝑋𝑝𝑋
𝑛1 + 𝑛2 … 𝑛𝑋
 
𝑣𝑎𝑟𝑖𝑎𝑛𝑐𝑒=
𝑛1𝑝1𝑞1+𝑛2𝑝2𝑞2…𝑛𝑋𝑝𝑋𝑞𝑋
(𝑛1+𝑛2…+𝑛𝑋)2
  
SD=√𝑣𝑎𝑟𝑖𝑎𝑛𝑐𝑒
2
  
 
Where: 
p = success probability (fusion) 
q = failure probability (1-P) 
 
𝑊𝑒𝑖𝑔ℎ𝑡𝑒𝑑 𝑎𝑣𝑒𝑟𝑎𝑔𝑒: 
=0.8779 
 
Standard deviation: 
= 0.0136 
Table 3: Literature Control - Average Fusion Rate 
 
To conclude, the average fusion rate for the control group is 87.79 % ± 1.36%. 
 
Range 
SD 
Weighted 
Average 
1 or 2 
Level 
Double 
Level 
Single 
Level 
Number of 
Patients 
Number of 
Manuscripts 
97% 
77% 
1.36% 
87.79% 
127 
195 
234 
488/556 
10 
(a total of 12 
study arms) 

                                                                                                                         
 
 
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A recently published systematic literature review, which analyzed published literature to 
evaluate the efficacy of lumbar arthrodesis for DDD patients 20, reported "As a whole, these 
12 studies including 1420 fusion patients showed…., the fusion rate was 89.3% (95% CI, 
84.4–94.2)" [emphasis added]. This correlates with the above values. 
 
It should be stressed that part of the studies reported in the literature used less stringent 
definitions of fusion than those used in various IDE studies for lumbar fusion, including the 
suggested IDE. For example, fusion rate of 74.6% was reported for the control group 
(Silhouette Spinal Fixation System) of the Dynesys Spinal System (Zimmer Spine) 
(P070031), and a fusion rate of 88.1% was reported for the control group (LT-CAGE 
Lumbar Tapered Fusion Device filled with ICBG) in P000058. Use in less stringent fusion 
definitions results in the relatively higher fusion rates reported in the literature. Further, per 
FDA’s recommendations, the definition of the angular motion in the proposed IDE is even 
more rigorous (i.e. 3° versus 5°) than the fusion definition of previous IDE studies.   
 
B. 
 ODI 
The following tables summarize the ODI results, as described in the articles referenced 
above.  
The ODI (also known as the Oswestry Low Back Pain Disability Questionnaire) is a 
validated tool used to measure a patient's level of pain and functional disability. The test is 
considered the ‘gold standard’ of low back functional outcome tools 21. Past IDE studies 
success criterion required 15-point improvement.  
 
A total of five level I and II studies (321 patients) from the control group reported the 
outcome of the Oswestry Disability Index (ODI) for DDD patients who underwent lumbar 
arthrodesis with pedicle screws, and are used as historical controls.   
                                                 
20   Phillips FM1, Slosar PJ, Youssef JA, Andersson G, Papatheofanis F.Spine (Phila Pa 1976). Lumbar Spine 
Fusion For Chronic Low Back Pain Due TO Degenerative Disc Disease: A Systematic Review. Spine 
2013;38(7):E409-422. 
21   Fairbank JC, Pynsent PB. The Oswestry Disability Index. Spine 2000 Nov 15;25(22):2940-52. 

                                                                                                                         
 
 
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One study (Zigler) reported outcome for homogenous single level DDD cohort and is, 
therefore, directly comparable to the proposed IDE study. In three studies (Fritzell, 
Hackenberg and Brox), subgroup stratification for single- and double level DDD was not 
provided for ODI outcome parameter (please note, that Hackenberg et al. provide ODI 
results stratification for one/two-level for all subjects (a total of 30 DDD patients and 22 
isthmic spondylolisthesis patients); the overall ODI improvement is relatively similar for 
patients undergoing one- or 2-level surgery). Delamarter reported outcome for 
homogenous 2-level DDD cohort. Overall, the final ODI value for all five studies is similar, 
suggesting that the differences in patient population do not preclude their pooling to enable 
a general comparison between the literature control and IDE study group. 
 
Results from three studies (Zigler, Hackenberg and Delamarter) that evaluated ODI at one 
and two-year follow-up visits suggest that the number of patients that experienced a 
clinically meaningful change in ODI does not change significantly from one to two years, 
allowing pooling of both one and two year results. 
 
ODI outcome reported in the five manuscripts, and calculated weighted average of values, 
are presented in the tables below. The weighting factor was the number of patients in each 
study. 
 

                                                                                                                         
 
 
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Table 4: Literature Control - Oswestrey Disability Index (ODI) Outcome 
 
Single 
Level 
Double 
Level 
Procedure 
Diagnosis 
Cohort 
Size 
ODI 
Baseline 
ODI 
12 Months 
ODI 
24  Months 
Improvement (Δ) 
(ODIbl-ODIlast f. u.) 
% Improvement 
(Δ ODI/ ODIbl) 
Fritzell 
2002 (Arm I) N24=43 * 
N24=21 * 
ALIF or PLIF 
+ PLF + PSS 
DDD 
N24=65* 
47.3 ± 10.9 
- 
38.5 ± 18.9 
8.8 
(19%) 
Fritzell 
2002 (Arm 
II) 
N24=35♦ 
N24=27 ♦ 
PSF + PSS 
DDD 
N24=59 ♦ 
48.4 ± 11.6 
- 
33.6 ± 17.9 
14.8 
(30%) 
Zigler 
2007 
N24=71 
- 
ALIF + PLF  
+ PSS 
DDD 
N24=71 
62.7 ± 10.3 
40.7 
39.8 ±  24.3 
22.9 
(37%) 
Hackenberg 
2005 
No level stratification 
TLIF +  PLF  
+ PSS 
DDD 
N36=30 
58.4 ± 18.4 
37.5 ± 19.3 
37.0 ± 24.8 
21.4 
(37%) 
Delamarter 
2009 
- 
N24=61 
ALIF + PLF 
+ PSS 
DDD 
N24=61 
64.8 ± 9.5 
41.1 ± 23.0 
38.7 ± 24.1 
26.1 
(40%) 
Brox 
2003 
No level stratification 
PLF + PSS 
DDD 
N12=35 
42.0 ± 11.0 
26.4 ± 16.4 
- 
15.6 
(37%) 
 
*  The ODI evaluation was conducted for 65 patients, however the stratification to one and two-level was given to 64 patients that were radiographically evaluated. 
♦   The ODI evaluation was conducted for 59 patients, however the stratification to one and two-level was given to 62 patients that were radiographically evaluated. 
 

                                                                                                                         
 
 
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Table 5: Literature Control - ODI Reference Results 
 
As can be seen, the similar values were reported for one- and 2-level and for one- and two years, 
justifying the pooling of the results. 
 
In addition, the recently published systematic literature review (Phillips et al.) mentioned above 
analyzed published literature to evaluate the efficacy of lumbar arthrodesis for DDD patients, 
reported "As a whole, these 12 studies including 1420 fusion patients showed a weighted average 
improvement in ODI function of 24.7 ± 6.2/100 (47.2% change; 95% CI, 41.3–53.1)" [emphasis 
added]. This correlates with the values listed in the tables. 
 
 
Points 
Range 
Number of Manuscripts 
Number of 
Patients 
Weighted 
Average 
12m Δ Improvement 
(single level) 
22.0  
1 
71 
22.0 
24m Δ Improvement 
(single level) 
22.9  
1 
71 
22.9 
12m Δ Improvement 
(double level) 
23.7 
1 
61 
23.7 
24m Δ Improvement 
(double level) 
26.1 
1 
61 
26.1 
12m Δ Improvement  
(1 & 2 levels ) 
20.9 – 
23.7 
4 
197 
23.4 
24m Δ Improvement  
(1 & 2 levels ) 
8.8 - 26.1 
4 
(total of 5 study arms) 
286 
18.5 
Range 
Weighted Average 
Improvement (%) 
Weighted Average 
Improvement (Δ) 
Number of 
Patients 
Number of 
Manuscripts 
26.1 
(40%) 
8.8 
(19%) 
32.63% 
18.22 
321 
5 
(a total of  
6 study arms) 

                                                                                                                         
 
 
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C. 
VAS Pain  
The following table summarizes the VAS (pain) results, as described in the articles referenced 
above.  
 
A total of five level I & II studies (321 patients) from the control group reported pain outcome 
for DDD patients who underwent circumferential lumbar arthrodesis with pedicle screws, and 
are used as historical controls.  
 
The Visual Analog Scale (VAS) for Pain is a unidimensional measure of pain intensity, which 
has been widely used in diverse adult populations 22. It is a continuous scale comprised of a 
horizontal visual analog scale of 100 mm length. It is anchored by two verbal descriptors (No 
Pain and Severe Pain). Values here refer to back pain as VAS leg pain is reported in only one 
study (Fritzell). Please note that also in Frizell study the back pain was the dominant pain 
component (compared to leg pain). 
 
One study (Zigler) reported VAS pain outcome for homogenous single level DDD cohort and 
was therefore analogous to the proposed IDE study. In the three studies (Fritzell and Hackenberg 
and Brox), subgroup stratification for single- and double level was not provided for VAS pain 
outcome parameter. Please note, that Hackenberg et al provided VAS (pain) results stratification 
for one/two-level for all subjects (a total of 30 DDD patients and 22 isthmic spondylolisthesis 
patients); the overall VAS improvement is relatively similar for patients undergoing one- or 2-
level surgery). Overall, the final VAS score for most of the studies is similar, suggesting that the 
differences in patient population do not preclude their pooling to enable a general comparison 
between the literature control and IDE study group. 
 
 
                                                 
22  Mc Cormack HM, Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. 
Psychol Med 1988;18:1007–1019. 

                                                                                                                         
 
 
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As can be seen in the table below, VAS improvement results for the same patients at 12 months 
and 24 months postoperatively are very similar and results can be pooled from one to two years. 
 
VAS pain outcome reported in the five manuscripts and calculated weighted average of values 
are presented below. The weighting factor was the number of patients in each study. Where 
applicable (Hackenberg), VAS score results were converted to a 100-point score, for consistent 
interpretation.  
 
 

                                                                                                                         
 
 
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Table 6: Literature Control - Visual Analogue Scale (VAS) Outcome 
 
 
Single 
Level 
Double 
Level 
Procedure 
Diagnosis 
Cohort 
Size 
VAS 
Baseline 
VAS 
12 m 
VAS 
24 m 
Improvement (Δ) 
(VASIbl-VASlast f.u.) 
% Improvement 
(Δ VAS/VASbl) 
Fritzell 
2002 (Arm I) N24=43* 
N24=21* 
ALIF or PLIF 
+ PLF + PSS 
DDD 
N24=65* 
65.6 ± 15.2 
- 
45.7 ± 26.7 
19.9 
(30%) 
Fritzell 
2002 (Arm 
II) 
N24=35♦ 
N24=27 ♦ 
PSF + PSS 
DDD 
N24=59 ♦ 
63.3 ± 13.3 
- 
40.4 ± 23.9 
22.9 
(36%) 
Zigler 
2007 
N24=71 
- 
ALIF + PLF  
+ PSS 
DDD 
N24=71 
75 ± 14.6 
42 ± 28 
43 ± 31.6 
32 
(43%) 
Hackenberg 
2005 
No level 
stratification 
TLIF +  PLF  
+ PSS 
DDD 
N36=30 
83 ± 26 
45 ± 23 
48 ± 28 
35 
(42%) 
Delamarter 
2009 
- 
N24=61 
ALIF + PLF 
+ PSS 
DDD 
N24=61 
74.7 ± 13.6 
40.3 ± 27.9 
38.4 ± 29.8 
36.3 
(49%) 
Brox 
2003 
No level 
stratification 
PLF + PSS 
DDD 
N12=35 
62.1 ± 14.5 
39.4 ± 25.5 
- 
22.7 
(37%) 
 
*  The ODI evaluation was conducted for 65 patients, however the stratification to one and two-level was given to 64 patients that were radiographically 
evaluated. 
♦  The ODI evaluation was conducted for 59 patients, however the stratification to one and two-level was given to 62 patients that were radiographically 
evaluated. 

                                                                                                                         
 
 
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Table 7: Literature Control - VAS Reference Results 
 
 
As can be seen, the overall patient population had a VAS improvement of around 30 points. 
In addition, similar values were reported for one- and 2-level and for one- and two years, 
justifying the pooling of the results. 
 
 
In addition, Phillips et al. published recently systematic literature review, which analyzed 
published literature to evaluate the efficacy of lumbar arthrodesis for DDD patients, and 
reported that "As a whole, these 12 studies including 1420 fusion patients showed a weighted 
average improvement in back pain of 36.5 ± 17.2/100 points (43.3% change; 95% CI, 31.5–
55.1)." 
    
 
 
 
Point  
Range 
Number of 
Manuscripts 
Number of 
Patients 
Weighted 
Average 
12m Δ Improvement 
(single level) 
33  
1 
71 
33  
24m Δ Improvement 
(single level) 
32  
1 
71 
32  
12m Δ Improvement 
(double level) 
34.4 
1 
61 
34.4  
24m Δ Improvement 
(double level) 
36.3 
1 
61 
36.3  
12m Δ Improvement  
(1 & 2 levels ) 
22.7 - 38 
4 
197 
32.4 
24m Δ Improvement  
(1 & 2 levels ) 
19.9 – 36.3 
4 
(total of 5 study arms) 
286 
28.6 
Range 
Weighted Average 
Improvement (%) 
Weighted Average 
Improvement (Δ) 
Number of 
Patients 
Number of 
Manuscripts 
36.3 
(49%) 
19.9 
(30%) 
39.47% 
27.96 
321 
5 
(a total of  
6 study arms) 

                                                                                                                         
 
 
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D. 
Adverse Events  
The description of adverse events in the manuscripts used for the literature review is not 
uniform; some authors describe the adverse events in detail, while other do not (see the tables 
in Appendix B, listing all adverse events mentioned in the control articles). In light of this 
limitation, the Company used the safety data provided in Table 7 of the FDA’s Executive 
Summary for DDD patients (n=1,350; complications=921; re-operation=814). The relevant 
section (i.e., DDD patients) of the said table is presented below: 
 
It is not possible to simply sum the event rates for each adverse event to establish a control 
adverse event rate for several reasons. The table above does not specify the adverse event 
severity or device relatedness. Further, the same type of adverse event, such as skin irritation, 
may be categorized with various degrees of severity depending on the actions taken to resolve 
ADEVERSE EVENT 
RATE 
Screw Malposition  
0.5% 
Screw Loosening  
0.4% 
Rod/Plate/Screw Breakage  
1.3% 
Construct Disassembly  
0.1% 
Bone Fracture  
- 
Graft Settling/Displacement 
0.1% 
Pseudoarthrosis  
5.9% 
Bleeding/Vascular Injury  
0.7% 
Neurologic Injury  
0.8% 
Nerve Root injury 
0.3% 
Spinal Cord Injury  
0.0% 
Back/Leg Pain (Radiculopathy)  
0.7% 
Dural Tear/CSF Leak  
1.0% 
Wound problems (Hematoma/Seroma)  
0.3% 
Infection/Sepsis  
3.9% 
Superficial  
2.6% 
Deep  
0.9% 
Skin Irritation  
0.3% 
Cardiac  
0.2% 
Respiratory  
0.4% 
Gastrointestinal  
0.3% 
Urologic/Reproductive  
0.1% 
Reoperation/Revision 
10.9% 
Removal of Hardware 
5.5% 

                                                                                                                         
 
 
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the event. In addition, it is possible that several adverse events occurred in the same patient, 
which means summing the rates would lead to an erroneously high adverse event rate. 
Therefore, the Company believes that a conservative estimate of relevant adverse events can 
be obtained by summing all device-related serious adverse events, all reoperations/revisions 
and all neurological injuries.  
Therefore, the rate of failure of devices in the control group for safety reasons is 13.5% which 
includes all device-related serious adverse events (including screw loosening, implant 
breakage and construct disassembly), reoperations/revisions and neurologic injuries.  
 
5.3     INCLUSION CRITERIA 
A subject will be considered eligible for inclusion in this study only if all of the following 
criteria apply: 
1. Subject has degenerative disc disease (DDD) at one level, from L2 to S1 vertebrae, 
with up to Grade I spondylolisthesis.   
DDD is defined as back pain and/or radicular leg pain with degeneration of the disc 
confirmed by patient history, radiographic studies, and physical examination, with 
one or more of the following factors (as measured radiographically, either by CT, 
MRI or plain film, myelography, discography, etc.): 
 
osteophyte formation of facet joints or vertebral endplates; 
 
decreased disc height, on average by > 2 mm;  
 
scarring/thickening of ligamentum flavum, annulus fibrosis, or facet joint 
capsule; 
 
herniated nucleus pulposus; 
 
facet joint degeneration/changes;  
 
vacuum phenomenon. 
2. 
Subject is candidate for single level intervertebral fusion, with or without posterolateral 
fusion, with implantation of intervertebral body fusion device and supplemental 
fixation.  
3. 
Subject age is between 21 – 72 years, and subject is skeletally mature.  

                                                                                                                         
 
 
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4. 
Pre-operative low back and/or leg/s pain (debilitating pain that causes a significant 
disturbance of the routine daily physical activities) ≥ 40 mm on a 100 mm Visual 
Analogue Scale (VAS).   
5. 
Pre-operative Oswestry Disability Index (ODI) score ≥ 40 percentage-point, 
indicating at least moderate disability (interpreted as moderate/severe disability). 
6. 
Low back and/or leg/s pain is unresponsive to prior non-surgical management for a 
minimum of six months. Non-operative treatment includes pain medication, physical 
therapy and/or injections.  
7. 
Patient must understand and sign the informed consent. 
8. 
Patient is willing and able to meet the proposed follow-up schedule including return 
to follow-up visits and complete necessary study paperwork.  
9. 
Patient is willing and able to follow the postoperative management program.  
 
 
5.4       EXCLUSION CRITERIA   
A subject will not be considered eligible for inclusion in this study if any of the following 
criteria applies: 
1. 
Previous fusion or fusion attempts, including anterior fusion or posterolateral 
fusion, at the index level. 
2. 
Previous fusion or fusion attempts at the adjacent levels. 
3. 
Prior decompression procedures that include removal of soft and bone tissue at the 
index or adjacent levels. 
4. 
Patient is not skeletally mature. 
5. 
Degenerative spondylolisthesis greater than Grade I.  
6. 
Spinal instability at the index level with ≥ 3 mm translation and/or ≥ 5 degrees 
angulation. Determination of instability will be assessed using flexion/extension 
lateral view radiographs. 
7. 
Isthmic spondylolisthesis. 
 
 
  

                                                                                                                         
 
 
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8. 
Radiographically confirmed moderate or severe spinal stenosis with associated 
neurogenic claudication. 
Definitions: 
 
Radiographically confirmed moderate/severe stenosis is defined as 
reduction of ˃50% of central and/or foraminal canal diameter compared to 
the adjacent uninvolved levels.  
 
Neurogenic claudication is leg, groin, or buttock pain and/or numbness that 
worsens with walking or erect posture and is relieved with flexion of the 
spine. 
9. 
Systemic infection or infection at the site of surgery. 
10. 
Metabolic bone disease, such as osteopenia, osteoporosis, and osteomalacia. A 
screening Questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis 
Risk Estimation), will be used to screen patients who require a DEXA bone mineral 
density measurement. If DEXA is required, exclusion will be defined as measured T-
score less than or equal to -2.5 (WHO definition). 
11. 
History of Paget’s disease or other bone pathologies, whether acquired or 
congenital, 
including 
renal 
osteodystrophy, 
untreated 
or 
uncontrolled 
hyperthyroidism, 
hypothyroidism, 
or 
hyperparathyroidism, 
Ehrlers-Danlos-
syndrome, osteogenesis imperfecta, achondroplasia, tuberculosis. 
12. 
Personal and/or familial history NF2, and/or spinal tumor. 
13. 
Ankylosing spondylitis. 
14. 
Diffuse idiopathic skeletal hyperostosis (DISH) syndrome.  
15. 
Active hepatitis (viral or serum) or HIV positive, renal failure, systemic lupus 
erythematosus, or any other significant medical conditions which would substantially 
increase the risk of surgery. 
16. 
Immune deficiency disease.   
17. 
Patient is receiving immunosuppressive or long-term steroid therapy. 
18. 
Active malignancy or other significant medical comorbidities. 
19. 
All concomitant diseases that can jeopardize the functioning and success of the 
patient.  

                                                                                                                         
 
 
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20. 
Allergy to any component of the investigational device, including carbon fiber-
reinforced polyetheretherketone (CFR-PEEK), titanium, and tantalum. 
21. 
Pregnancy, or female subject interested in become pregnant during the duration of the 
study.  
22. 
Current chemical dependency (e.g., drug and/or alcohol abuse, according to DSM-V 
definition), as well as those with a history of such abuse. 
23. 
Uncontrolled depression, psychosis, or other symptoms of a mental disorder that, in 
the investigator’s opinion, likely would make the subject unable to comply with the 
study procedures and could affect the study outcome. 
24. 
Treatment with drugs that may interfere with bone metabolism, such as 
glucocorticosteroids, calcitonin, bisphosphonates, bone therapeutic doses of 
fluoride, bone therapeutic doses of vitamin D or vitamin D metabolites, and 
treatment by chemotherapy.  
25. 
Morbid obesity (BMI ≥ 40). 
26. 
Current smokers (including 3 months prior to surgery). 
27. 
Scoliosis, Cobb angle greater than 11°.  
28. 
Vertebral fractures. 
29. 
Severe muscular, neural or vascular diseases that endanger the spinal column.  
30. 
Missing bone structures, due to severely deformed anatomy or congenital anomalies, 
which make good anchorage of the implant impossible.  
31. 
Paralysis. 
32. 
Current use of other investigational drug or device. 
33. 
The patient is involved in a worker’s compensation case or spine-related litigation. 
34. 
The patient is a prisoner. 
Note: The time elapses between the diagnostic studies required for entry and enrolment into 
the study is limited to up to three months.  
 
5.5     NUMBER OF PATIENTS AND PATIENT SELECTION 
Patients Number: 
A total of 55 patients will be recruited for the study (up to 15 subjects will be recruited in this 
site). Their results will be combined with an additional 45 patients from the ongoing OUS 

                                                                                                                         
 
 
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study, the details of which are presented in the Investigator Brochure. When combined with 
the patients from the ongoing OUS study, 55 patients was deemed sufficient for this 
confirmatory, single-arm study. Therefore, the total effective sample size is about 100 
patients.  
Patients Selection:  
In order to be included in this study, patients will have to fulfill all the Inclusion Criteria and 
none of the Exclusion Criteria, as well as to sign and date the Informed Consent Form. 
All patients' full medical history will be recorded and all patients will undergo a complete 
general physical and neurological examination. Plain A-P and lateral X-Ray films, as well as 
lateral flexion-extension X-Rays, will be performed prior to surgery.  
Neurological examination will be performed to confirm that the patient' clinical signs and 
symptoms are consistent with the baseline disease level/s demonstrated per imaging.  
An anesthesiologist will assess the patient for general anesthesia, according to the routine 
practice. 
 
5.6      STUDY SITES 
Up to eight sites may participate in the study. At least two sites will be in the USA, recruiting 
at least 30 patients.  
 
5.7      STUDY DURATION  
The study is expected to last up to 36 months (total duration), including patient enrollment 
and a post-operative follow-up period of 24 months per subject.  
 
The primary safety and effectiveness analyses will be performed at 24 months. The collected 
information will be submitted to the FDA as part of a 510(k) Premarket Notification after all 
patients have completed 24 months of follow-up. In case of satisfactory results, the Company 
intends to submit the results of the study to the FDA, after all patients have completed the 12 
months follow-up, as part of a Premarket Notification (510(k)). It is emphasized, that all 
patients will be additionally followed at 24-month time point, and afterwards annually, until 
the last patient completed 2-year follow-up. It is noted, that at the time all subjects from IDE 

                                                                                                                         
 
 
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study reach 12-month follow-up, it is expected that 2-year supportive data from the original, 
ongoing OUS clinical study with the investigational device will be available. 
Patients will be followed and assessed both clinically and radiographically after surgery at 
follow-up visits.  
Evaluation time points shall be conducted at the following intervals: 
 
Preoperatively (with up to 3 months between the diagnostic studies to enrolment); 
 
Operatively; 
 
Postoperatively, at discharge from hospital; 
 
Postoperatively, at 6 weeks ± 2 weeks from surgery;  
 
Postoperatively, at 3 months ± 2 weeks from surgery;  
 
Postoperatively, at 6 months ± 1 month from surgery;  
 
Postoperatively, at 12 months ± 2 months from surgery. 
 
Postoperatively, at 24 months ± 2 months from surgery. 
Afterwards, subjects will be clinically evaluated annually, until the last patient has completed 
2-year follow-up. 
 
At baseline, discharge, and at follow-up sessions, radiographic evaluation, pain and 
functionality evaluations, and subject's overall well-being assessment shall be performed. 
Assessment of subject' satisfaction shall be performed postoperatively, starting at 6-week 
follow-up.    
Complications/adverse events shall be evaluated operatively and at each evaluation time 
points, as well as throughout the study.   
 
Refer to Sections 5.9 and 5.10 for a detailed schedule and assessment description, 
respectively. 
 
5.8       MISSING DATA 
Incomplete information may be available for a subject for various reasons: 
 
Subject stopped participation in the study at its own request; 
 
Continuing the follow-up is not possible/subject lost to follow-up; 

                                                                                                                         
 
 
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 
Subject stopped participation in the study at the Investigator’s discretion. 
 
In general, in cases where information will be available for a certain missing data point from a 
previous and from the next follow-up, an interpolation of the values shall be performed. 
Missing data from patients that were lost to follow-up will be handle by "last value carried 
forward" approach (i.e., the last value obtained from a subject will be used for the analysis).  
 
5.9         PROCEDURES 
5.9.1       PREOPERATIVE MANAGEMENT 
a. 
The Investigator will select the subjects according to the inclusion and exclusion 
criteria, as described in Sections 5.3 and 5.4, respectively.  
b. 
The Investigator will be acquainted with the technique and instrumentation required 
for the procedure. Training will be provided by the Sponsor or its authorized 
representatives in accordance with the Training Protocol (Appendix C). 
c. 
The Investigator will be familiar with the Protocol of the clinical trial. 
d. 
Signed written Informed Consent must be obtained for all subjects. 
e. 
The patients shall be instructed to refrain from the use of NSAIDS for two weeks 
prior to surgery. 
f. 
All female subjects who are of child bearing age should present a negative beta-
HCG blood (pregnancy) test or submit a signed statement that she is using at least 
one conventional contraceptive method and that to the best of her knowledge she is 
not pregnant. Such woman shall be informed of the risks involved in participating in 
the study while pregnant and cautioned to inform the study personnel if she becomes 
pregnant during the timeframe of the study.  
 
Pre-procedure assessment will be conducted according to the outline provided in the Case 
Report Forms (CRFs) booklet.  
Pre-procedure examination includes (refer also to Table 8 below): 
 
Demographic data 
 
Full medical history, including concomitant medications  

                                                                                                                         
 
 
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 
Physical examination  
 
Neurological examination  
 
X-Ray evaluation 
The results of the said examinations shall be recorded. 
During the pre-operative session, the following forms shall be completed (refer also to Table 
9 below): 
 
Pre-operative CRF 
 
Patient baseline questionnaires (Visual Analogue Scale (VAS, for back and leg 
pain assessment), Oswestry Disability Index (ODI), and 12-Item Short Form Health 
Survey (SF-12) 
 
5.9.2      SURGICAL PROCEDURE 
The surgical procedure is described in the system Surgical Technique (Appendix A).  
The Operative CRF shall be completed. 
In case of an adverse event, the appropriate CRF should be filled. 
 
5.9.3       POSTOPERATIVE MANAGEMENT 
In general, postoperative management shall be conducted according to the description in the 
CRFs.  
 
Immediate post-operative management should be as per routine hospital standard of care.  
 
Prior to discharge, the following examinations/tests shall be performed (refer also to Table 8 
below and to the description in the Discharge CRF):  
 
Physical examination   
 
Neurological Examination  
 
X-Ray evaluation 
The results of the said examinations shall be recorded on the Discharge CRF. 
In addition, the patient shall be interviewed regarding adverse events; in case of an adverse 
event, the appropriate form should be filled. 

                                                                                                                         
 
 
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The patients shall be instructed to refrain from the use of NSAIDS for three months post-
operatively. 
 
During follow-up visits, the following post-operative examinations/tests shall be performed 
(refer also to Table 8 below and to the description in the post-operative CRFs):  
 
Physical examination  
 
Neurological Examination   
 
X-Ray evaluation 
The results of the said examinations shall be recorded. 
At every follow-up visits the following forms shall be completed (refer to Table 9): 
 
Post-operative CRF  
 
Patient follow-up questionnaires (VAS (pain), ODI, SF-12, VAS (donor site pain, if 
applicable), and VAS (satisfaction))  
In addition, the patient shall be interviewed at each follow-up visit regarding adverse events, 
and the appropriate form should be filled. If a non-scheduled postoperative visit results from 
such an event, it should be noted on the form.  
 
Table 8 below lists the assessment schedule and examinations. 

                                                                                                                         
 
 
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Table 8: Assessment Schedule 
Description 
Pre-
Procedure 
Operation Discharge 6 Weeks 
Visit 
3 Months 
Visit 
6 Months  
Visit 
 12 Months 
Visit  
24 Months  
Visit  
Annual  
Visit § 
Unscheduled 
Visit 
Inclusion/Exclusion Criteria 
√ 
 
 
 
 
 
 
 
 
 
Informed Consent  
(signed & dated) 
√ 
 
 
 
 
 
 
 
 
 
Demographic & Medical 
History  
√ 
 
 
 
 
 
 
 
 
 
Physical Examination 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Neurological Examination 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
X-Rays (AP, Lateral and 
Flexion/Extension) 
√          Fluoroscopy 
√ * 
√ * 
√ * 
√ 
√  
√  
√  
√ ** 
Patient Questionnaires 
(VAS (Pain), ODI, SF-12, 
VAS (Satisfaction)) 
√ ¤ 
 
 
√ 
√ 
√ 
√ 
√  
√  
 
CT Scan 
 
 
 
 
 
√ ¥ 
√ ¥ 
√ ¥ 
√ ¥ 
 
AE Recording 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
§     Will be performed after the 24-month follow-up, until the last patient completes 2-year follow-up. 
*    Except for flexion/extension X-rays.  
**  Will be performed only if required according to the physician discretion.  
¤    Except for patient satisfaction VAS. 
¥    CT scan will be conducted for patients in whom bridging bone status cannot be determined in X-Rays. 
Table 9 below lists the Questionnaires and Forms that need to be completed during baseline and postoperatively evaluations. 

                                                                                                                         
 
 
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Table 9: Forms/Questionnaires to be Completed at Pre-Op. and Follow-Up Visits 
Form Type 
Pre- 
Operation 
Operation Discharge 
6 weeks 
Post-Op. 
3 Months 
Post-Op. 
6 Months 
Post-Op. 
12 Months 
Post-Op. 
24 Months 
Post-Op.  
Annual  
Visit * 
Unscheduled 
Visit 
Pre-Op. CRF 
(Enrollment and 
Baseline Forms) 
 
 
 
 
 
 
 
 
 
 
Operative CRF 
 
 
 
 
 
 
 
 
 
 
Discharge CRF 
 
 
 
 
 
 
 
 
 
 
Post-Op. CRF 
 
 
 
 
 
 
 
 
 
 
Unscheduled Visit 
CRF 
 
 
 
 
 
 
 
 
 
 
Medications CRF – 
Follow Up  
 
 
Medications Form should be completed at discharge and follow-up sessions, 
in case any concomitant medication was used during hospitalization or since last visit, respectively 
Adverse Event CRFs 
(AEs, SAE, 
Additional Surgery) 
 
When applicable 
Protocol Deviation 
 
When applicable 
Conclusion CRF 
 
 
At 24 Months, or when applicable 
VAS (Pain),  
ODI & SF-12 
 
 
 
 
 
 
 
 
 
 
VAS (Donor Site 
Pain), if applicable 
 
 
 
 
 
 
 
 
 
 
VAS (Satisfaction)  
 
 
 
 
 
 
 
 
 
 
*    Will be performed annually after reaching the 24-month follow-up, until the last patient completes 2-year follow-up         

                                                                                                                         
 
 
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Subjects who shall withdraw from the study will have the Conclusion CRF completed 
for them upon their request to withdraw from the study. The reason for withdrawal 
and any alternative treatment suggested to the patient shall be indicated on the form. 
In case a subject who is lost to follow up returns at a later stage, this will be indicated 
as a remark on the Conclusion CRF along with the reason the patient missed the 
previous follow-up session(s). 
 
5.10       EVALUATION OF PRIMARY OUTCOME MEASURES  
5.10.1     FUSION EVALUATION 
Fusion will be evaluated radiographically, by A-P, lateral and flexion/extension X-
Rays (flexion/extension films will be used for the assessment of angular and 
translational motions). As detailed below, in case of inconclusive findings regarding 
bridging bone, a CT scan will also be performed, and evaluated by the core lab.  
 
Fusion assessment shall be made postoperatively, starting at 6 months and at each 
follow-up session afterwards.   
 
Each fusion area (between the endplates, at right posterolateral, and at left 
posterolateral, as applicable) will be assessed separately.  
 
All radiographs will be read by two independent, board-certified, radiologists from 
Medical Metrics, Inc., with experience in musculoskeletal imaging, blinded to clinical 
outcomes, and without any financial interest in CarboFix Orthopedics, to ensure 
consistent reading of the radiographs and elimination of bias. In the case of a 
disagreement between the two radiographic assessors, a third independent reviewer 
will evaluate the radiographic images to adjudicate the findings.  
 
Please refer to Appendix D for radiographic protocols, including Image Acquisition 
Protocol, Image Transfer Protocol, and Radiographic Evaluation Protocol. All said 
protocols were provided to CarboFix by Medical Metrics, Inc.   
 

                                                                                                                         
 
 
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Fusion Radiographic Patient Success is defined when all the following radiographic 
endpoints are met at 24 months: 
a. Angular motion ˂ 3º; AND  
b. Translational motion ˂ 3 mm; AND 
c. Presence of continuous bridging bone between the involved motion segment, 
i.e.: 
 Presence of interbody (between endplates) bridging bone and absence of 
radiolucency > 50%; OR 
 Presence of left posterolateral bridging bone; OR 
 Presence of left posterolateral bridging bone.  
 
Regarding angular motion, reporting of subjects will be provided in the following 
three groups:  
1.  those with ≤ 3º total angular motion,  
2.  those between 3º and 5º of motion, and  
3.  those with ≥ 5º of motion.  
 
In case bone graft would be placed in the interbody space as well as posterolaterally, 
on both sides, bridging would be assessed in each of the three areas. Bridging in any 
one area would be considered adequate to document the presence of affirmative 
bridging. 
 
Radiolucency will be evaluated as the percent coverage of radiolucent lines along the 
graft / endplate interface. There will be a single assessment for the superior and 
inferior bone / graft interfaces combined. Radiolucency will be evaluated primarily 
from lateral views. The view (neutral, flexion or extension) showing the most severe 
extent of radiolucency will be used to document the assessment.  
Radiolucency will be used to document bone resorption. Particularly in the early 
stages of healing, poor conformance of the graft with the endplate geometry, i.e. poor 
“fit and fill”, will not be identified as radiolucency.   
 
 

                                                                                                                         
 
 
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Radiolucency will be graded in accordance with the following definitions: 
None: No radiolucent lines along the interbody graft / endplate interface. 
Mild:  ≤ 25% radiolucent lines along the interbody graft / endplate interface. 
Moderate: 26% - 50% radiolucent lines along the interbody graft / endplate 
interface. 
Severe: > 50% radiolucent lines along the interbody graft / endplate interface. 
 
Non-fusion will be indicated in the following cases:  
Angular motion ≥ 3° OR translational motion ≥ 3 mm OR absence of continuous 
bridging bone, i.e.: 
 Absence of interbody bridging bone and presence of radiolucency >50%; 
AND  
 Absence of left posterolateral bridging bone; AND 
 Absence of right posterolateral bridging bone. 
 
Possibly fusion: Patients in whom the status of bridging bone is inconclusive will 
undergo fine cut CT scan to determine bridging bone and fusion status. At each 
timepoint, starting at 6 months, any inconclusive X-Rays assessment relates to 
bridging bone shall be repeated within window, using CT.  
 
Information regarding the CT scans (including the procedures for obtaining and 
transmitting the CT scans) is presented in the Radiographic Protocol (Appendix D).  
Definition of bridging bone evaluated in CT scan is as follows (on top of motion 
evaluated by flexion/extension X-Rays):  
Presence of continuous bridging bone between the endplates; or between the right 
facets, pedicle and/or transverse processes; or between the left facets, pedicle and/or 
transverse processes, as applicable.  
 
The fusion rate obtained in the study shall be compared to the fusion rates reported in 
the literature (as summarized in Section 5.2.1). 
 

                                                                                                                         
 
 
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5.10.2    PAIN AND FUNCTION EVALUATION 
Pain and functionality will be assessed using dedicated questionnaires.  
VAS (Back, Right Leg, and Left Leg Pain): The assessment of pre- and post-
operative pain shall be performed using scores determined from measurements of 
responses to pain question for each location (i.e., low back, right leg, and left leg), 
provided on a 100 mm Visual Analog Scale (VAS). The anchor points are “No Pain” 
(0 mm) and “Severe Pain” (100 mm). Patients will be instructed to draw a single line 
across the scale at the point that best described their level of pain.  
The pain VAS assessment will be administered preoperatively as well as at each 
postoperative visit, starting at 6 weeks. 
  
ODI (Functionality): The Oswestry Disability Index (ODI) will be used to assess 
function. The ODI questionnaire is based on patient’s responses to ten questions, 
which focus on pain intensity, personal care, lifting, walking, sitting, standing, 
sleeping, sex life, social life, and traveling. Each question has six possible answers. 
The responses to each question ranges from zero to five points. A lower numeric 
score represents a better pain and disability status regarding that variable (0 points for 
functionality with no associated pain or no extra pain; 5 points for inability to perform 
function due to pain). A total ODI score is determined by adding the scores of the 
individual questions and dividing that total by the maximum possible total score (50 if 
all questions are answered); this yields a percentage. Therefore, ODI scores shall be 
presented ranging from 0% to 100%, with a lower percentage indicating less pain and 
disability.  
The ODI questionnaire will be administered preoperatively as well as at each 
postoperative visit, starting at 6 weeks visit.  
 
Clinically Meaningful Improvements –  
 Individual patient clinically meaningful improvement with respect to pain is 
defined as postoperative improvement at 24 months of at least 20 mm on a 100 
mm VAS from the baseline level. Data regarding pain improvement will be 
provided for all pain components (i.e., low back, right leg and left leg). The 

                                                                                                                         
 
 
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above improvement criterion of 20/100 mm refers to the dominant pain 
component for each patient. For example: if the preoperative VAS (pain) for a 
given patient was 90 (low back), 60 (right leg), and 40 (left leg), improvement 
of at least 20 mm will be required for the back pain component. Improvement 
in both legs, though, will be also reported. 
 Individual patient clinically meaningful improvement with respect to 
functionality is defined as postoperative improvement at 24 months of at least 
15 points on the ODI graded on a 100-point scale as compared to baseline 
assessment.  
 
It is noted, that the indicated improvement values in pain and function are regarded 
clinically meaningful and were used in other, IDE studies for similar devices.  
 
Average improvement and standard deviation for VAS (pain) and ODI, as well as the 
proportion of patients that met the success criterion for VAS and ODI, will be 
reported. The VAS and ODI results obtained in the study shall be also compared to 
VAS and ODI results reported in the literature (as summarized in Section 5.2.1).   
 
5.10.3 SAFETY EVALUATION 
The safety evaluation will be based on the reported complications and adverse events 
(AEs), including subsequent surgical interventions and neurological status. 
Complications/Aes shall be evaluated at each follow-up session, as well as throughout 
the study. 
  
1. 
Complications/Adverse Events 
All the reported complications/adverse events, whether device-related or not, 
including "anticipated" complications, will be recorded.  
Refer to Section 5.14.4.1 for adverse event definitions.   
 
 
 

                                                                                                                         
 
 
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2. 
Subsequent Surgical Intervention  
Information regarding subsequent interventions will include category of procedure, as 
defined below, the reason for the procedure and whether or not the subsequent 
procedure constitutes a study failure.  
Subsequent surgical intervention will be categorized as a revision, removal, re-
operation, or supplemental fixation at the affected level/s, as defined hereinafter.  
Revision – a second procedure that adjusts or in any way modifies or removes part of 
the original implant configuration, with or without replacement of a component. A 
revision may also include adjusting the position of the original configuration. 
Removal – a procedure where all of the original system configuration are removed 
with or without replacement. 
Reoperation – any surgical procedure at the involved level/s that is not removal, 
modification, or addition of any components to the system (e.g., irrigation and 
debridement).  
Supplemental Fixation – a procedure in which additional instrumentation not under 
study in the Protocol is implanted. 
Subsequent interventions in spinal studies include epidural injections, the 
implantation of spinal stimulators, and rhizotomies.  
 
3. 
Neurological Status 
A neurological examination will be performed preoperatively and at discharge, and at 
all postoperatively visits, to assess neurological status. The evaluation of neurological 
status will include motor, sensory, reflex, straight leg raising, and tenderness 
assessments, as hereby described. Each component shall be assessed separately on 
each anatomical side (left, right). The following paragraphs describe the five 
neurological examinations.  
The motor evaluation measures the muscle strength in major muscle groups (Gluteus 
Maximus (hip extension); Iliopsoa (hip flexion); Quadriceps (knee extension); 
Hamstrings (knee flexion); Anterior Tibial Group (ankle dorsiflexion); Extensor 
Hallucis 
Longus 
(great 
toe 
extension); 
Posterior 
Tibial 
(ankle 
plantar 
flexion/eversion); and Flexor Halluces (great toe flection)). Muscle strength is 
evaluated on a 6-point scale ranging from 0 to 5 according to the following key 

                                                                                                                         
 
 
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describing the ability of the patient to move the lower extremities against resistance 
provided by the examiner:  
 
0 – no movement;  
 
1- muscle contraction;  
 
2 – lateral movement;  
 
3 – against gravity;  
 
4 – against moderate resistance;  
 
5 – against full resistance.  
 
Light-touch will test sensation for all lumbar and sacral dermatomes in comparison to 
the contralateral site. The sensation shall be graded as equivalent (normal), impaired, 
absent, as compared to the contralateral side. 
 
Reflexes (Patella and Achilles) are evaluated according to Bate’s Reflex Scale (a 5-
point scale ranging from 0 to 4) as follows:  
 
0 – no reflex;  
 
1 – somewhat diminished, low normal;  
 
2 – average, normal reflex;  
 
3 – brisker than average;  
 
4 – very brisk, hyperactive.  
 
Straight leg raising is assessed by measurement of the degree of movement required 
to reproduce symptoms. A positive test is considered when the patient reports 
worsening of pain between 30 and 70 degrees of hip passive flexion while knee is 
extended. 
 
Tenderness will be evaluated by palpation of the lower spine area – lumbar 
paraspinal region, lumber spinous process, sacroiliac joint, and sciatic notch. 
Tenderness shall be graded as negative or positive (i.e., palpation provokes painful 
sensation). 
 
 

                                                                                                                         
 
 
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Patient Success –  
Individual patient success with respect to safety is defined as: 
 
No worsening in neurological status (motor, sensory, reflex, straight leg 
raising, and tenderness assessments) and no new permanent neurological 
deficits present for at least 2 successive visits at or beyond 6 months (out to 
24 months); 
 
Absence of device-related serious adverse events through 24 months; 
 
Absence of subsequent surgical interventions at the index level through 24 
months. 
 
5.11 EVALUATION OF SECONDARY OUTCOME MEASURES 
A. 
Patient's Overall Well-Being and Satisfaction 
Subject's overall well-being and satisfaction will be assessed using dedicated 
questionnaires. 
 
SF-12 (Subject Overall Well-Being): 
Subject's overall well-being (quality of life) will be assessed using the 12-Item Short 
Form Health Survey (SF-12), which is a multipurpose short-form quality of life 
instrument with 12 questions selected from the SF-36 Health Survey. SF-12 
questionnaire is designed to measure general health status from the patient's point of 
view. Results are expressed in terms of two meta-scores: the Physical Component 
Summary (PCS) and the Mental Component Summary (MCS). The PCS Score is a 
composite of the Physical Functioning, Role Functioning, Bodily Pain and General 
Health Scales within the SF-12 instrument. The MCS is a composite of the Vitality, 
Social Functioning, Role-Emotional and Mental Health Scales within the SF-12 
instrument. The SF-12 is a normative based instrument. PCS and MCS are computed 
using the rating on 12 questions from 0 to 100, where a 0 score indicates the lowest 
level of health and 100 indicates the highest level.  
The SF-12 questionnaire will be administered preoperatively as well as at each 
postoperative visit, starting at 6 weeks visit.  
 

                                                                                                                         
 
 
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VAS (Patient Satisfaction):  
Patient satisfaction will be assessed using a 100 mm VAS, completed by the patient. 
Satisfaction scores shall be obtained from patient responses, and shall be expressed in 
millimeters (mm). The anchor points are “Completely Not Satisfied” (0 mm) and 
“Completely Satisfied” (100 mm). Patients shall be instructed to draw a single line 
across the scale at the point that best described their level of satisfaction.  
VAS questionnaire for satisfaction will be administered at each postoperative visit, 
starting at 6 weeks visit. 
 
B. 
Donor Site Pain  
The assessment of pain at the donor site (iliac crest) shall be performed using scores 
determined from measurements of responses to pain question, provided on a 100 mm 
VAS. The anchor points are “No Pain” (0 mm) and “Severe Pain” (100 mm). Patients 
for which bone graft was harvested from their iliac bone will be instructed to draw a 
single line across the scale at the point that best described their level of pain at the 
donor site.  
VAS questionnaire for donor site pain will be administered at each postoperative visit, 
starting at 6 weeks visit.  
 
C. 
Operative Information 
Parameters related to the surgery, such as blood loss and operation time will be also 
evaluated for all patients participating in the study.  
The volume of blood loss during operation will be recorded for each patient, and 
average blood loss and standard deviation will be reported in cubic centimeter (cc). 
Operation time (skin-to-skin) will be recorded for each patient, and average operation 
time and standard deviation will be reported in minutes. 
  
5.12       STUDY SUCCESS CRITERIA  
The results of the study at 12 months and 24 months postoperatively for all 
participating subjects will be evaluated, with reference to the reported results from the 

                                                                                                                         
 
 
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literature, as summarized in Section 5.2.1. In addition, assessment of success rate will 
be conducted at each time point, as applicable. 
In addition to evaluating individual patient success as the primary composite 
endpoint, each element of the composite will be evaluated individually as secondary 
endpoints, as described below. 
Fusion – Success for the fusion outcome measure will be defined as two year fusion 
rate comparable to the two and one year fusion rates presented in the literature. The 
pooled results of the Company literature research (for patients with DDD treated with 
pedicle screws with PLIF/ALIF/TLIF and/or PLF), as presented in Section 5.2.1, 
demonstrated at 12 and 24 months postoperatively fusion rates in the different studies 
ranging from 77% to 97%.   
As discussed in Section 5.2.1.A, the weighted average for the fusion rate of the ten 
articles is 87.79%.  Based on the literature, we believe our fusion rate will be 88%.    
The assumed fusion rate of 88% has a 95% confidence interval of ±6.4% for 100 
patients. Notably, the lower bound of this confidence interval, 81.6%, is within the 
range of the fusion rates reported in the selected literature. 
 
Safety – Success with regard to safety outcome measure is defined as no worsening in 
neurological status (motor, sensory, reflex, straight leg raising, and tenderness 
assessments) and no new permanent neurological deficits (present for at least 2 
successive visits at or beyond 6 months), absence of device-related serious adverse 
events, and absence subsequent surgical interventions at the index level, through 24 
months, comparable to neurological deficit, device-related serious adverse events, and 
subsequent surgical interventions rates presented in the literature.  
Based on the literature review in FDA’s Executive Summary, the rate of these events 
in the literature control is 13.5%.  
Therefore, the Company estimates that the adverse event rate for these events will be 
13.5%. With a sample size of 100 patients, this adverse event rate has a 95% 
confidence interval of ±6.7%.   
As indicated above, it is believed that at the time all subjects from the IDE study 
complete one year follow-up, supporting safety data for 24 months will be available 
for about 45 patients from the ongoing, OUS study.  

                                                                                                                         
 
 
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Pain - Individual patient, clinically meaningful, improvement with respect to pain is 
defined as postoperative improvement at 24 months of at least 20 mm on a 100 mm 
VAS from the baseline level.  
Value of 73% of patients with ≥20 mm improvement. This value is selected as it is 
consistent with the performance of the Silhouette Spinal Fixation System reported in 
P070031. 
 
Function - Individual patient, clinically meaningful, improvement with respect to 
function is defined as postoperative improvement at 24 months of at least 15 points on 
the ODI graded on a 100-point scale as compared to baseline assessment.  
Value of 55% of patients with ≥15 points improvement. This value is selected as it is 
consistent with the performance of the control group reported in P050010. 
 
Individual Patient Success (Overall Success) 
Individual patient success (i.e., overall success) will be determined at 24 months and 
is defined as a composite primary endpoint. An individual subject will considered a 
success if all of the following criteria are met:  
 
Presence of continuous bridging bone between the involved motion segment at 
24 months, i.e.: 
 
Presence of interbody bridging bone and absence of radiolucency > 
50%; OR 
 
Presence of left posterolateral bridging bone; OR 
 
Presence of left posterolateral bridging bone.  
 
No motion on flexion/extension films at 24 months (success is defined as 
angular motion ˂ 3º and translational motion ˂ 3 mm); 
 
Improvement of at least 20 mm on a 100 mm VAS from baseline level at 24 
months;  
 
Improvement of at least 15 points on the ODI graded on a 100 point scale at 
24 months as compared to baseline; 
 
No worsening in neurological status (motor, sensory, reflex, straight leg 
raising, and tenderness assessments) and no new permanent neurological 

                                                                                                                         
 
 
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deficits present for at least 2 successive visits at or beyond 6 months (out to 24 
months); 
 
Absence of device-related serious adverse events through 24 months; 
 
Absence of subsequent surgical interventions at the index level through 24 
months.  
The study will be considered a success if the overall success rate for the CarboClear 
Device is 41%. This value is selected as it is consistent with the performance of the 
control groups reported in P050010 and P070031. 
 
5.13      STATISTICAL ANALYSIS 
5.13.1   SAMPLE SIZE JUSTIFICATION 
Fifty five (55) patients will participate in the IDE study. However, the statistical 
analysis will be conducted for a total sample size of 100 patients as the Company is 
adding data from ongoing OUS sites to data collected according to this IDE. FDA 
confirmed that the proposed IDE sample size, in addition to the ongoing OUS data, 
would be sufficient. It is emphasized, that prospectively enrolled patients at OUS sites 
will participate in the study presented in this IDE (i.e., will be part of the 55 patients 
of the IDE study), and will follow the same protocol that representing homogenous 
cohort of DDD patients with up to Grade I spondylolisthesis and no greater than mild 
stenosis. Only currently enrolled patients in the ongoing OUS sites that are adequately 
per IDE protocol (about 45 patients) will be considered in the statistical analysis. 
Adequacy for OUS study patients being included in the statistical analysis will be 
based, mainly, on patient meeting the eligibility criteria (inclusion/exclusion) for the 
IDE study, i.e., DDD patients, with up to Grade I spondylolisthesis and/or with up to 
mild stenosis (the ongoing OUS study was approved for more heterogenic 
population). Other parameters, as detailed below, are very similar when comparing 
the ongoing OUS study and the study suggested in this IDE: The same system and 
surgical technique are used in both studies. The IDE study includes the use of an 
interbody fusion device while the OUS study does not. Thus, the data from the OUS 
study may be regarded as worst case in terms of fusion rates as only posterolateral 
fusion was made and interbody fusion device was not used. Patient population is 

                                                                                                                         
 
 
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considered similar in both studies (demographically, as well as indications wise, as 
non-DDD patients will not be included in the statistics for the IDE study). The 
endpoints for the IDE study are also evaluated in the ongoing OUS study, using the 
same assessment tools: fusion (radiographs), safety, pain (VAS), function (ODI), and 
patient well-being (SF-12). Follow-up time points are similar in the ongoing OUS 
study (4 weeks, 3 months, 6 months, 12 months and 24 months) and the suggested 
IDE study (6 weeks, 3 months, 6 months, 12 months, and 24 months, and then 
annually, until the last patient completed 2-year follow-up).   
As it is estimated that data for about 45 patients will be available from the ongoing 
OUS study, the total sample size is effectively 100 patients.  
 
It is noted, that the suggested investigation is a confirmatory study, aimed at 
supporting the safety and effectiveness of the CarboClear System. As indicated 
before, comprehensive pre-clinical testing was conducted for the system, with good 
results, substantially equivalent to the results of cleared predicate devices (metal, 
rigid, pedicle screw systems). In addition, interim results from the ongoing, OUS 
study with the CarboClear System support the safety and effectiveness of the system 
for DDD patients (as summarized in the Investigator Brochure, the OUS trial enrolls 
DDD patients, as well non-DDD patients/patient with DDD and other pathologies. 
The latter may be regarded as worst case with respect to pedicle screw 
instrumentation and fusion in comparison to DDD patients). 
Based on the above, and taking into account the selection of narrow indication for the 
study that results in homogenous population, the number of 55 subjects for this 
confirmatory study is thought to be sufficient (with statistical analysis of 100 
patients).   
 
5.13.2 POOLABILITY OF DATA 
All data obtained from up to 8 sites participating in this study will be pooled into a 
single database for which data analysis will be performed.  
Poolability is considered to be appropriate as all sites will use the same study Protocol 
and Appendices (such as Case Report Forms). Also, all investigational teams will 

                                                                                                                         
 
 
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receive the same training by the Sponsor representative. The appropriateness of 
pooling data from multiple centers is necessarily enhanced by training all 
participating centers to follow the same protocol, with, among other things, clearly 
defined inclusion and exclusion criteria for study participation. Periodic monitoring 
visits shall be conducted to verify full understanding and fulfillment of the procedure 
at all sites. In addition, performance and evaluation of X-Rays images will be 
performed using the same means and definitions, according to written radiographic 
protocol, by the same independent reviewers. Likewise, independent reviewers 
(clinical events committee) will assess all adverse events to determine the severity of 
the events and their relationship to the procedure and investigational device (please 
refer to Section 5.14.4). Thus, this multi-center study includes standardization of 
subject enrollment, data collection and evaluation, and adverse event reporting and 
evaluation, with all sites following the requirements of the same Protocol.  
Prior to pooling the data, the demographic information items will be reviewed to 
verify that their average values for all sites are within one standard deviation. 
Furthermore, the Company will perform poolability analyses of baseline 
characteristics and cage type in order to confirm the homogeneity of the entire patient 
population.  
In particular, before combining the US and OUS data (e.g., patients from US and 
patients from OUS in the proposed study; as well as patients from the proposed IDE 
study and patients from the ongoing OUS study) the baseline demographics and 
prognostic characteristics between the groups will be compared to evaluate the 
poolability of the US and OUS data. The characteristics to be compared include: 
•   Age 
•   Gender 
•   Pre-operative VAS 
•   Pre-operative ODI 
•   Diagnosis (DDD, Degenerative Spondylolisthesis ≤ Grade I, Spinal Stenosis < 
40%, or other) 
•   Previous spinal surgical treatment (yes/no) 
•   Type of interbody fusion device used (for subjects participating in the IDE 
study) 

                                                                                                                         
 
 
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These characteristics will be compared using a t-test or a Wilcoxon rank sum test for 
continuous variables and a Chi-square test or a Fisher’s exact test for categorical 
variables, as appropriate. If the OUS data is similar to the US data then the data will 
be pooled and analyzed as a single group. If the US and OUS data are dissimilar, then 
the combining of the two datasets may need to be reevaluated. The reasons for 
dissimilarity will be investigated and the effect of investigational treatment in the 
presence of the disparate results will be discussed. In addition, primary analysis 
results stratified by US and OUS sites will be presented.    
 
With regards to the ongoing OUS study – as described in the above Section 5.13.1, 
poolability of data for the statistical analysis is deemed eligible.  
  
5.13.3 ANALYSIS POPULATIONS 
Intent-to-Treat (“ITT”): All patients treated with the device. 
Per-Protocol (“PP”): All patients who did not have a major protocol violation and 
who completed all study visits. 
The primary analysis will be based upon the ITT population. Additional analyses 
using the PP population will also be presented in the final report. 
 
5.13.4 STATISTICAL ANALYSIS OF DATA 
In general, the statistics for numerical variables shall be presented as mean ± standard 
deviation, median, minimum and maximum values (range), and sample size 
(continuous data). Categorical data will be presented as counts (numbers) and 
percentage of the total (rate). In addition, 95% confidence intervals will be presented 
for the fusion and adverse events rates. Furthermore, subgroup summary statistics will 
be calculated where necessary.  
Where adequate, comparison between subgroups (e.g., with/without mild stenosis; 
with/without prior discectomy) shall be presented with differences (e.g., P-values). It 
should be noted that comparisons between subgroups are supportive analyses; these p-
values will not be adjusted for multiplicity.  

                                                                                                                         
 
 
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Adverse events (AE) data will be listed individually and summarized. Overall AE 
results will be presented both on a per-subject basis and per-event basis (i.e., total 
number of subjects with each event and total number of events reported).   
Results of AE seriousness and device-relatedness will be presented as well.  
The report of AEs based on specific type of event will be according to the following 
AE terms, listed in the table below, and in accordance with FDA list of risks 
applicable for pedicle screw spinal systems (FDA’s Executive Summary, Table 11). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In addition, as per the FDA recommendation, the adverse events will be further 
analyzed according to the Adverse Events table provided in Section 5.14.4.2. 
 
Patients who withdraw from the study (following implantation of the investigational 
device), are lost to follow-up, or for whom data is missing, will be analyzed 
individually based on the information already available for the patient. In general, if 
sufficient data will be available for the patient based on previously gathered 
ADEVERSE EVENTS 
Implant Malposition  
Implant Loosening  
Device Breakage  
Construct Disassembly  
Bone Fracture  
Graft Settling/Displacement 
Loss of Correction 
Pseudoarthrosis  
Bleeding/Vascular Injury  
Neurologic Injury  
Back/Leg Pain (Radiculopathy)  
Dural Tear/CSF Leak  
Wound problems  
Infection/Sepsis  
Skin Irritation  
Cardiac  
Respiratory  
Gastrointestinal  
Reoperation/Revision 
Death 

                                                                                                                         
 
 
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information (e.g., at previous follow-up sessions) or if, in cases where fusion occurs 
prior to withdrawal and no adverse events have been observed, the patient may be 
regarded as a success.  
 
5.14 
SUMMARY OF RISK ANALYSIS 
5.14.1 POSSIBLE HAZARDS 
The risks and possible adverse events associated with the use of CarboClear Pedicle 
Screw System and the discussed procedure are expected to be similar to- and are not 
expected to be at a higher rate than those related to other pedicle screw-based devices 
and procedures available on the market.  
Those risks/possible adverse events include: 
(a) risks associated with undergoing surgery; 
(b) risks associated with spine surgery; 
(c) risks associated with fusion surgery of the lumbar spine; and 
(d) risks associated with the use of the CarboClear Pedicle Screw System. 
The individual risks associated with each of the above groups are provided below. 
 
Risks Associated with Undergoing Surgery 
 Infection/Sepsis. 
 Development of respiratory problems, e.g. atelectasis, bronchitis, pneumonia, 
etc. 
 Haemorrhage of blood vessels and/or haematomas occlusion, seroma, edema, 
hypertension, embolism, stroke, excessive bleeding, phlebitis, wound necrosis, 
wound dehiscence, damage to blood vessels, or other types of cardiovascular 
system compromise. 
 Deep venous thrombosis, thrombophlebitis and/or pulmonary embolus. 
 Damage to lymphatic vessels and/or lymphatic fluid exudation. 
 Reactions to the drugs or anesthetic agent used during and after surgery. 
 Ileus, gastritis, bowel obstruction or loss of bowel control or other types of 
gastrointestinal system compromise. 

                                                                                                                         
 
 
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 Reactions to transfused blood. 
 Incisional pain. 
 Change in mental status.  
 Death. 
 
Risks Associated with Spine Surgery  
 Loss of neurological function (e.g., sensory or motor), including paralysis 
(complete or incomplete), appearance of radiculopathy, dysesthesias, 
hyperesthesia, anesthesia, paresthesia, and/or the development or continuation 
of pain, numbness, neuroma, spasms, sensory loss, tingling sensation, and/or 
visual deficits. 
 Cauda equina syndrome, neuropathy, neurological deficits (transient or 
permanent), paraplegia, paraparesis, reflex deficits, irritation, arachnoiditis, 
and/or muscle loss. 
 Dural tear experienced during surgery could result in the need for further 
surgery for dural repair, a chronic cerebral spinal fluid leakage or fistula, and 
possible meningitis. 
 Herniated nucleus pulposus, disc disruption or degenerative changes or 
instability at, above, or below the level of surgery. 
 Loss of or decrease in spinal mobility or function. 
 Loss of proper spinal curvature, correction, height and/or reduction. 
 Bone fracture or bone loss or decrease in bone density, possibly caused by 
stresses shielding at, above, or below the level of surgery. 
 Tissue or nerve damage caused by improper positioning and placement of 
implants or instruments. 
 Vascular damage due to surgical trauma or presence of the device could result 
in catastrophic or fatal bleeding. Malpositioned implants adjacent to large 
arteries or veins could erode these vessels and cause catastrophic bleeding in 
the late postoperative period. 
 Bursitis.  

                                                                                                                         
 
 
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 Scar formation possibly causing neurological compromise or compression 
around nerves and/or pain. 
 Inability to resume activities of normal daily living. 
 Reproductive system compromise, including sterility, retrograde ejaculation, 
and sexual dysfunction. 
 Urinary retention or loss of bladder control or other types of urological system 
compromise. 
 Risk of radiation exposure preoperatively, during surgery and following 
operation, during follow-up sessions (e.g., fluoroscopy, X-Rays, and optionally 
CT scans). 
The series of radiographs required for this study are similar to the standard of 
care for patients with similar traditional surgical procedures. The risk of any 
side effects from this low level of exposure is very small. It is estimated that 
the total millirems will be less than 200 millirems per visit (for a 4 view x-ray) 
or no more than 1300 millirems for the duration of this study. This exposure 
can be compared to the allowable annual radiation dose for nuclear 
medicine/radiation oncology workers of 1800 millirems per year.23 The 
consequences of this radiation are small, but can include developing cancer 
later in life from the radiation.24 Radiation exposure associated with computed 
tomography (CT) scans of the lumbar spine is higher, and may approach 6 
milliSieverts, or the equivalent of approximately 730 days of natural 
background radiation (at 3 mSv/year). The consequences of CT scans are 
small, but can include developing cancer later in life, and potential reactions to 
contrast agent.24 
 
 
 
                                                 
23http://www.fda.gov/RadiationEmittingProducts/RadiationEmittingProductsandProcedures/Medicallm
aging/MedicaiX-Rays/ucm175028.htm 
24http://www.fda.gov/RadiationEmittingProducts/RadiationEmittingProductsandProcedures/Medicallm
aging/MedicaiX-Rays/ucm115317.htm 
 

                                                                                                                         
 
 
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Risks Associated with Fusion Surgery of The Lumbar Spine 
 Graft settling/displacement. 
 Non-union (or pseudarthrosis), delayed union or mal-union. 
 Donor site pain. 
 Risks pertaining to the use of allograft (if applicable), including infection, 
fever, incomplete bone ingrowth, delayed fusion or non-union, hypercalcemia 
or transient hypercalcemia, disease transmission and undesirable immune 
response. 
 
Risks Associated with The Use of The CarboClear Pedicle Screw System. 
 Disassembly, loosening, bending or fracture of any or all of the implant 
components. 
 Implant migration. 
 Foreign body (allergic) reaction to the implants, debris, including possible 
staining, autoimmune disease, tumor formation and/or scarring. 
 Pressure on the surrounding tissues or organs. 
 Pressure on the skin from component parts in patients with inadequate tissue 
coverage over the implant, possibly causing skin penetration, irritation, 
fibrosis, neurosis, and/or pain. 
 
Additional surgical intervention may be necessary to correct some of the possible 
adverse events. Surgical intervention may be a revision surgery, a removal procedure, 
re-operation, or supplemental fixation. 
 
This list of potential risks is presented, in the same manner, in the patient Informed 
Consent document, in the Case Report Forms, and in the IFU (Package Insert) for the 
system.  
 
5.14.2 RISK REDUCTION MEASURES 
Risk management activities are carried following the guidelines provided in ISO 
14971 Standard (Medical Devices – Application of Risk Management to Medical 

                                                                                                                         
 
 
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Devices). The analysis of risks was performed using the Failure Mode and Effect 
Analysis (FMEA) in its extended version (FMECA), in accordance ISO 14971 and 
IEC 812 (Failure Mode and Effects Analysis).  
 
CarboFix activities, from initial design stages, are aimed at minimizing as possible 
faults, malfunctions, incidents, etc., related to the device. In order to reduce the risk of 
patient (or user) harm or a fault/damage to the device during its usage, the following 
measures are taken: 
a. 
Design activities according to written design control procedures; 
b. Risk management activities, including risk analysis; 
c. 
Biocompatibility evaluation;  
d. Conducting pre-clinical, comprehensive bench testing and cadaveric study;  
e. 
Manufacturing according to quality system requirements (e.g., production 
according to approved specifications, drawings and instructions; performing 
quality controls to incoming raw material, following production stages, and to 
finished devices; etc.); 
f. 
Providing a clear Instructions for Use document (IFU) and Surgical 
Technique. Among other things, these documents include description of the 
system and its components (including figures), indications for use and 
contraindications, possible adverse events, warnings and precautions, 
instructions regarding system preparation, surgical procedure description, 
information regarding the compatibility of the product with other devices, and 
information regarding product packaging and sterilization.  
g. Conducting additional validations and verifications, as applicable, such as 
sterilization validation. 
 
The following paragraphs specifically address the risks indicated above, and the 
measures by which those potential risks are minimized. 
 
A. Risks Associated with Undergoing Surgery 
General operative-related complications (such as infection/sepsis, bleeding/vascular 
injury, respiratory and cardiac complications, anesthesia, wound complications and 

                                                                                                                         
 
 
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pain, etc., as listed above) are expected to be similar in nature and not in higher rates 
compared to those seen with other pedicle screw systems, as the surgical procedure is 
the same.  
As the implantation procedure is similar to that used for other pedicle screw system 
implantation, using similar surgical instruments, and as cleared interbody fusion 
device is used, no additional/special hazards are expected to rise from the operation 
procedure itself.  
It is noted, that the implantation procedure and the performance of the surgical 
instruments were also evaluated during cadaveric study. 
 
In addition, the CarboClear System is currently under multi-center study conducted 
out-of-the-US. So far, 47 patients were already treated with the system, with a follow-
up duration of up to over one year (40 of which had diagnosis that complies with the 
indications proposed in the IDE (i.e., DDD patients with up to Grade I 
spondylolisthesis). The following adverse event, which may be categorized as related 
to undergoing surgery, was reported in the said study: 
In one patient, fever was developed following uneventful operation and discharge (5 
days following surgery). CT images revealed well-positioned implants with no root 
irritation. The surgical wound was healed, with no infection. Blood cultures were 
negative. The patient was hospitalized and treated with intra-venous antibiotics for 
three days, and was then discharge from the hospital with additional 2 weeks of 
antibiotics. Fever was probably related to pneumonia. The patient healed and is doing 
well.  
 
B. Risks Associated with Spine Surgery  
Complications associated with spine surgery (as listed above) are expected to be 
similar in nature and not in higher rates compared to those seen with other pedicle 
screw systems, as the implant components design and dimensions, and the surgical 
procedure for their implantation (as well as the use of the cleared intervertebral fusion 
device), are similar.  
As the implantation procedure is similar to that used for other pedicle screw system 
implantation, using similar surgical instruments, no additional/special hazards are 

                                                                                                                         
 
 
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expected to rise from the spinal procedure in comparison to other, similar spinal 
surgeries.  
It is noted, that the implantation procedure and the performance of the surgical 
instruments were evaluated during cadaveric study. 
Regarding the risk of radiation exposure, no additional risk of radiation exposure is 
expected prior to-, during the implantation of the CarboClear device as well as during 
follow-up sessions, compared to radiation exposure associated with similar spinal 
implants that are being investigated in clinical studies. The risk of radiation exposure 
during implantation procedure is also expected to be the same as that for cleared 
pedicle screw systems. It is expected, though, that subjects participating in a clinical 
study for spinal implants may undergo additional imaging at follow-up sessions and 
thus the risk of radiation exposure may be slightly higher for this population 
compared to patients undergoing spinal surgery with a cleared device.  
 
In addition, data from the on-going OUS clinical investigation (for the 40 patients that 
comply with the indications for the proposed IDE study) supports the similarity 
between the CarboClear spinal surgery parameters with those of other, similar 
devices: 
Operation Time - Average total operation time recorded during the said 40 surgeries 
with the CarboClear System was 115.1 minutes (±23.4 minutes), ranging from 72 to 
185 minutes. Operation time reported for the surgeries carried to date is similar to that 
reported by others for this type of surgeries (for example, Kim et al. 25 report average 
operation time of 196 minutes, and Dimar et al. 1 – 174 minutes).  
Blood Loss - Average blood loss recorded during the 40 surgeries was 379.4 cc 
(±125.6 cc), ranging from 200 cc to 600 cc. Blood loss reported for the surgeries 
carried to date is similar to that reported by others for this type of surgeries (for 
example, Dimar et al. 26 report average blood loss of 448.6 mL, and Kang at al. 27 - 
512.5 mL).  
                                                 
25  Kim KK, Lee SH, Lee YH, Bae SC, Suk KS, Clinical Outcomes of 3 Fusion Methods through the 
Posterior Approach in the Lumbar Spine. Spine 2006; 31 (12): 1351 – 1357. 
26  Dimar JR, Glassman SD, Burkus JK, Pryor PW, Hardacker JW, Carreon LY. Two-year fusion and 
clinical outcomes in 224 patients treated with a single-level instrumented posterolateral fusion with 
iliac crest bone graft. The Spine Journal 2009;9:880–885. 

                                                                                                                         
 
 
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Fluoroscopy Time - Average fluoroscopy time recorded during the 40 surgeries was 
38.7 seconds (±18.9 seconds), ranging between 20 and 100 seconds. Fluoroscopy time 
reported for the surgeries carried to date is similar to that reported by others for this 
type of surgeries (for example, Jones et al. 28 report fluoroscopy time of 1.4 minutes 
(i.e., 84 seconds) per case or 0.33 minutes per screw, in a series of 140 patients who 
underwent pedicle screw fixation; Mulconrey 29 reported mean fluoroscopic time of 
1.74 minutes (104.4 seconds) with lumbar spine instrumentation). 
 
The on-going clinical investigation with the CarboClear device also supports the 
proper visualization of implant components, either during operation or at follow-up 
period. This minimizes the risk of pedicle screws malpositing, and subsequent adverse 
events such as nerve tissue injury and possible additional surgical intervention. Pre-
clinical evaluation of implant components was conducted during cadaveric study, 
using three imaging modalities (X-Rays, CT and MRI).     
In addition, the following adverse event, that may be categorized as related to spinal 
surgery, was reported in the OUS study (for the 40 DDD patients): 
About 1 week post-operation the patient complained of radicular pain, with no motor 
deficiency and no fever. CT demonstrated mild compression and edema, with no 
nerve root irritation. The implants seemed well positioned and intact. The patient was 
re-operated (exploratory surgery), revealing mild compression at the surgery site. The 
instruments were well positioned and stable. During this surgery additional 
decompression at one level above the surgery was performed. All symptoms resolved 
after second operation, with improvement in pain and functionality parameters at 3 
months follow-up as compared to pre-operation data. 
                                                                                                                                            
27  Kang J, Howard A, Hilibrand A, Yoon ST, Kavanagh E, Boden S. Grafton and Local Bone Have 
Comparable Outcomes to Iliac Crest Bone in Instrumented Single-Level Lumbar Fusions. Spine 
2012;37(12):1083–1091. 
28  Jones DP, Robertson PA, Lunt B, Jackson SA, Radiation exposure during fluoroscopically assisted 
pedicle screw insertion in the lumbar spine. Spine 2000; 25 (12): 1538-41. 
29 Mulconrey DS, Fluoroscopic Radiation Exposure in Spinal Surgery: In Vivo Evaluation for 
Operating Room Personnel. J Spinal Disord Tech. 2013 Nov 7 [Epub ahead of print]. 
 
 
 

                                                                                                                         
 
 
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The event was categorized as not related to the device, and possibly related to the 
procedure. 
 
C. Risks Associated with Fusion Surgery of The Lumbar Spine 
Complications associated with lumbar fusion include, on top of spinal surgery risks 
indicated above, graft settling/displacement, non-union (pseudarthrosis), delayed 
union or mal-union, and donor site pain. Additional risks may be associated with the 
use of allograft (if used), as listed above. It is noted, that the CarboClear device may 
be implanted with autogenous and/or allogenic bone graft. 
 
Those complications are expected to be similar in nature and not in higher rates 
compared to those seen with other pedicle screw systems, as the surgical procedure 
and instruments used for fusion, as well as the cleared interbody fusion device and 
bone graft materials, are similar.  
 
Data from the on-going OUS clinical investigation accumulated so far (for the 40 
patients that comply with the indications for the proposed IDE study) support the 
safety and effectiveness of the CarboClear System and indicate the following fusion 
rates:  
 At 6 months (1 level): 25/26 patients (96.2%); 
 At 12 months (1 level): 3/3 patients (100%); 
 At 6 months (2 levels): 1/1 (100%).  
It is noted, that comparative bench testing conducted for the system (as detailed in the 
Investigator Brochure) supports the similar performance of the system and cleared, 
metal, pedicle screw systems in terms of both test results and failure modes. In 
particular, with respect to the ability of the CarboClear rods to provide for adequate 
stiffness to support fusion - long-term stability and stiffness of the CFR-PEEK rods 
were successfully evaluated in static and dynamic tests conducted for the entire 
implant construct, as well as in 4-point bending test and creep test conducted for the 
rods.  
 

                                                                                                                         
 
 
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As it is postulated, based on all the above, that the risk of non/delayed/mal fusion 
would not be at a higher rate than that seen for other cleared, rigid, pedicle screw 
systems, it is expected that the risk of re-operation due to those risks will also be at 
similar rate as the rate reported for other rigid pedicle screw systems.  
 
D. Risks Associated with The Use of The CarboFix Pedicle Screw System  
In general, risks related to the use of the device are mitigated by the following 
measures: 
 Implant components are similar in design and dimensions to those of other, 
cleared, rigid pedicle screw systems. As with other pedicle screw systems, the 
CarboClear components allow the surgeon to build an implant construct to fit 
the patient’s anatomical and physiological requirements (e.g., the screws and 
rods are provided in various dimensions, the pedicle screws comprise a 
polyaxial head, and the rods are provided either straight or curved, all of which 
provide for an implant construct that meets the anatomical needs of the 
patient); 
 The surgical instruments of the system and the surgical procedure are similar 
to those used with other, cleared, pedicle screw systems; 
 Extensive biomechanical study was performed, as summarized below and 
detailed in the Investigator Brochure, with results and failure modes equivalent 
to those of the predicate devices; 
 Supportive clinical data are available from OUS clinical trial, as summarized 
in the Investigator Brochure; 
 Training of the study investigators;  
 Providing IFU (Package Insert) and Surgical Technique documents, as 
detailed below; 
 The use of the system is limited to only experienced spinal surgeons with 
specific training in the use of this system; 
 The system is designed, processed, assembled, tested, and packaged according 
to the Company approved procedures. Wherever required, processes are being 

                                                                                                                         
 
 
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verified and validated according to the Company approved procedures and 
international standards. 
The specific risks are detailed below, with the manner of their mitigation. 
 
Implant Mechanical Failure - Disassembly, Loosening, Bending, Fracture or Migration 
The CarboClear device was tested in a comprehensive in-vitro study and a cadaveric 
study, to validate its design and to assess its performance (e.g., bone purchase and 
function) and integrity (of the components and construct). Pre-clinical testing included 
the following tests: 
 Static axial compression bending test (ASTM F 1717) 
 Static torsion test (ASTM F 1717) 
 Fatigue axial compression bending test (ASTM F 1717) 
 Fatigue lateral bending-axial rotation test 
 Wear debris evaluation following fatigue testing (ASTM F 1877) 
 Axial gripping capacity test (ASTM F 1798) 
 Flexion-extension moment test (ASTM F 1798) 
 Axial torque gripping capacity test (ASTM F 1798) 
 Pull-out test (ASTM F 2193, ASTM F 543) 
 Rod 4-point bend test (ASTM F 2193) 
 Titanium shell shear test (ASTM F 1044) 
 Rod creep test  
 Cadaveric study  
Where applicable, tests were conducted in a comparative manner, to FDA-cleared 
predicate devices (rigid pedicle screw systems). Bench testing demonstrated 
substantial equivalent results and same failure modes. Please refer to the Investigator 
Brochure, for detailed description of the said tests. 
Various tests, and in particular fatigue tests, were performed to verify no failure of the 
implant (e.g., breakage, deformation, or disassembly) will occur prior to fusion. In 
fatigue axial compression bending test, the device construct successfully completed 
five million cycles under a load of 300 N, corresponding to 83% of its ultimate load. 
Lateral bending-axial rotation fatigue tests, conducted to further support the system 

                                                                                                                         
 
 
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mechanical properties and the equivalency to rigid, metal, pedicle screw systems, 
demonstrated the device completed 5x106 cycles at high moment of at least 8.5 Nm 
with no failure.  
Macroscopic and microscopic examination of the devices following the said fatigue 
tests indicated no plastic deformation of the rods. No scarring formation was detected. 
Wear debris analysis following fatigue tests indicated that only small amount of CFR-
PEEK debris was generated following successful completion of 5x106 fatigue cycles at 
relatively high loads and/or moments.  
 
Regarding loosening/disconnection of implant components - the CarboClear device is 
designed to prevent movement between its components, immediately upon locking. 
The rod is secured to the screw using a taper locking element, that accommodates the 
rod and is introduced within the screw tulip. Loosening/disconnection of components 
was assessed in several tests following the guidelines set in ASTM F 1798, which 
were designed to evaluate the interconnection mechanism of the device. Additional 
tests which evaluated the entire CarboClear construct, including fatigue tests, also 
demonstrated that the locking mechanism of the system is effective and comparative to 
cleared rigid pedicle screw systems.  
 
It is noted, that the screw is provided with a thin titanium shell, thus bone-implant 
interface is similar to that of other, cleared, pedicle screws. 
Shear test was successfully conducted to verify the integrity and connection of the 
titanium shell to the CFR-PEEK screw.  
As for implant migration - pullout tests performed to the CarboClear pedicle screws 
demonstrated that their pullout strength is similar to that of cleared predicate devices. 
 
Nonunion, Delayed Union or Malunion 
 
Long-term stability and stiffness of the CFR-PEEK rods (adequate stiffness to achieve 
fusion) were evaluated in static and dynamic tests conducted for the entire construct 
(i.e., four screws and two rods), as well as in 4-point bending test and creep test 
conducted for the rods.  

                                                                                                                         
 
 
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The results of the said tests indicated excellent fatigue properties and similar stiffness 
as compared to titanium pedicle screw constructs and titanium rods. 
The results obtained for the creep test, following more than five weeks under a high 
continuous load of 450 N and at a temperature of 70° C (conditions which simulate a 
year at 37° C and extreme loading), demonstrate no plastic deformation to any of the 
rods and high creep resistance.   
 
Implant Malposition  
Similarly to implantation of other pedicle screw systems, the surgical procedure is 
monitored radiographically, to verify, among other things, proper location of the 
screws and final construct positioning. Radiographic evaluation is also performed 
post-operatively.  
The implant components of the CarboClear System are made of radiolucent material - 
CFR-PEEK, with metal radiopaque markers intended to enable implant visualization 
under imagine. Especially, the threaded portion of the pedicle screws is encased 
within a thin layer titanium shell. The titanium shell mark the borders of the screw 
thread and distal tip, thus facilitating proper insertion of the screws under fluroscopy 
visualization, as well as monitoring their location (e.g., relative to nerve tissue) and 
integrity post-operatively. The other implant components comprise a tantalum marker.   
In accordance with FDA recommendation, the Company has conducted cadaveric 
study in a human spine, demonstrating the visualization of the CarboClear implants 
using the following imaging modalities: MRI, CT and X-rays.  
It is emphasized, that due to the relative small metal content, the screws do not 
interfere with CT and MRI imaging while allowing screw visualization under X-rays. 
In addition, the implantation procedure and the performance of the surgical 
instruments were also evaluated during cadaveric study. 
 
Foreign Body Reaction to the Implant 
The implant components are made of CFR-PEEK (Ultra Reinforced-PEEK-
OPTIMA® (Endolign), by Invibio), with radiopaque markers.  

                                                                                                                         
 
 
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The screw threaded portion is encased within a thin shell made of pure titanium 
(conforming to ASTM F 67). The other CFR-PEEK components include a tantalum 
(per ASTM F 560) marker, embedded within the CFR-PEEK during molding process. 
The said materials are acceptable for use in long-term implants and exist in other, 
cleared spinal implants (including their combination).  
In addition, the different manufacturing processes (e.g., compression molding) do not 
include the use of any additive, releasing agent, etc. For a detailed biocompatibility 
evaluation, please refer to the Investigator Brochure.  
As indicated before, evaluation of wear debris generation was conducted following 
successful completion of five million fatigue cycles at relatively high loads and 
moments, as well as following device failure. Analysis of collected material 
demonstrated that only a small amount of CFR-PEEK debris was generated. The 
description of the wear debris tests is provided in the Investigator Brochure. 
 
Infection (Non-Sterile Device) 
Regarding the risk of infection due to non-sterile device - the implants will be 
supplied sterile (by moist-heat steam) and labeled for single use. The multi-use 
surgical instruments will be supplied non-sterile, to be steam sterilized by the user. 
The steam sterilizations for the system components were validated to assure SAL of 
10-6, and bioburden tests are conducted periodically. 
Information regarding the sterilization of the implants and the cleaning and 
sterilization of the reusable surgical instruments is provided in the Investigator 
Brochure. 
 
Regarding the ongoing OUS study - it is emphasized, that no device-related adverse 
events or device malfunctions were reported in any of the 47 patients implanted with 
the system. No failure was observed to any of the components implanted (about 180 
pedicle screws (and locking elements), with about 90 rods for all 47 patients 
operated).  
In addition, as indicated earlier, fusion - determined by X-Ray images indicating 
continuous fusion in between transverse processes and/or facet joints (AP and lateral 
X-Rays) – was indicated in the following rates (for the 40 DDD patients; please note 

                                                                                                                         
 
 
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that for part of the patients, evaluation of translational and angular motion using 
flexion/extension radiographs was also conducted): 
 At 6 months (1 level): 25/26 patients (96.2%); 
 At 12 months (1 level): 3/3 patients (100%); 
 At 6 months (2 levels): 1/1 (100%). 
 
The on-going clinical investigation with the CarboClear device also supports the 
proper visualization of implant components, either during operation or at follow-up 
period.  Also, no allergic reaction to the implant was reported.  
 
As it is postulated, based on all the above, that the risk of device 
breakage/loosening/disassembly/migration; non/delayed fusion; or foreign body 
reaction to the device, would not be at a higher rate than seen for other cleared, rigid, 
pedicle screw systems, it is expected that the risk of re-operation due to these risks 
will be at similar rate as the rate reported for other pedicle screw systems.  
 
On top of the above, all the operating instructions are described in the IFU and 
Surgical Technique documents (refer to Appendix A). The intended use, as well as 
inclusion/exclusion criteria for the clinical trial, are defined and detailed. The IFU 
(Package Insert) and Surgical Technique describe the safety and protective measures 
required when handling the system as well as providing a description of the system, 
all the procedures regarding system preparation, and operation procedures. Possible 
adverse events are described in the IFU. Relevant packing and sterilization data are 
also provided in the IFU as well as in the Company's Instrumentation Handling 
Instructions. The IFU and Surgical Technique provide specific information relating to 
implant selection and patient selection.  
Safe use of the system with other devices is established by using items that comply 
with the requirements set in the Surgical Technique/IFU, where applicable, and in the 
manner detailed in the Surgical Technique. Reference is made in the Surgical 
Technique to the IFU and vice versa.  

                                                                                                                         
 
 
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Please note, that the different components of the system (including surgical 
instruments), as well as the Surgical Technique and IFU, are designed in a similar 
manner, and include similar information to that provided with other pedicle screws 
systems available on the market. This further contributes to reducing the possibility of 
new hazards related to use of the system, and the risk of insufficient or inadequate 
information provided. 
The IFU and Surgical Technique documents are reviewed prior to their release, and 
are approved according to the Company's procedures. 
The device labels are also reviewed prior to their release, and are approved according 
to the Company's procedures. Wherever applicable, warnings regarding single use of 
components and the sterility of components are provided. The name of the 
component/content list, and catalogue and lot numbers are indicated on the items’ 
labels as well. 
 
5.14.3 POTENTIAL BENEFITS 
In general, patients may not experience any direct benefits.  
Based on the performance of other cleared pedicle screw systems that have 
successfully relieved symptoms of degenerative disc disease, and clinical experience 
with the investigational device outside the United States, there is reason to believe 
that the CarboClear Pedicle Screw System could also relieve DDD symptoms.  
 
5.14.4 ADVERSE EVENTS 
5.14.4.1 Definitions  
Adverse Event (AE) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs in subjects, users or other persons, whether or not related to the investigational 
medical device (including events related to the investigational medical device; and 
events related to the procedures involved).  
 
 
 

                                                                                                                         
 
 
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Serious Adverse Event 
Defined as one of the following events: 
a. 
Death;  
b. 
Serious deterioration in the health of the subject, that either resulted in: 
 
a life-threatening illness or injury, or 
 
a permanent impairment of a body structure or a body function, or 
 
in-patient or prolonged hospitalization, or 
 
medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
c. 
Event that led to fetal distress, fetal death or a congenital abnormality or birth 
defect. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required 
by the protocol, without serious deterioration in health, is not considered a 
serious adverse event. 
 
Adverse Device Effect  
Adverse event related to the use of an investigational medical device (including 
adverse events resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device, and any event resulting from use error or from 
intentional misuse of the investigational medical device).  
 
Serious Adverse Device Effect (SADE)  
Adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event.  
 
Device Deficiency  
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance (including malfunctions, use errors, and inadequate 
labeling). 
 

                                                                                                                         
 
 
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Unanticipated Adverse Device Effect  
Unanticipated adverse device effect means any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
 
5.14.4.2 Assessing and Reporting of Adverse Events 
All adverse events, adverse device effects and device deficiencies (collectively: 
“Adverse Events”) will be documented using the relevant Adverse Events Report 
Forms. In addition, each subject will be questioned about Adverse Events at each 
follow-up visit. Adverse Events discovered during a routine follow-up will be 
documented additionally on the relevant follow-up CRF.  
Adverse Events occurring during the study will be treated by established standards of 
care that will protect the life and health of the study subjects. 
Signs and symptoms of each Adverse Event should be described in detail and include 
start and stop dates, intensity, correlation with investigational device, action taken and 
outcome. 
The Investigator shall evaluate and document the following: 
1. whether any Adverse Events have occurred; 
2. the nature of the event; 
3. date of Adverse Event onset and duration; 
4. seriousness of the event (serious, moderate, mild/minor);  
5. relation to the investigational device (not related, possibly related, definitely 
related); 
6. Adverse Event outcome and the course taken to reach the outcome. 
The report of AEs based on specific type of event will be classified according to the 
following AE terms, listed in the table below, and in accordance with FDA list of risks 
applicable for pedicle screw spinal systems (FDA’s Executive Summary, Table 11). 
 
 

                                                                                                                         
 
 
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In addition, as per the FDA recommendation, the adverse events will be further 
classified according to the following Adverse Events table (as applicable to this study, 
e.g., no control group): 
 
 
ADEVERSE EVENTS 
Implant Malposition  
Implant Loosening  
Device Breakage  
Construct Disassembly  
Bone Fracture  
Graft Settling/Displacement 
Loss of Correction 
Pseudoarthrosis  
Bleeding/Vascular Injury  
Neurologic Injury  
Back/Leg Pain (Radiculopathy)  
Dural Tear/CSF Leak  
Wound problems  
Infection/Sepsis  
Skin Irritation  
Cardiac  
Respiratory  
Gastrointestinal  
Reoperation/Revision 
Death 

                                                                                                                         
 
 
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Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
All Adverse Events1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
(x %) 
x 
x 
(x %) 
x 
Operative Site/Implant/Spine Surgery Focused Events 
 (Includes Perioperative Systemic Events Related to the Operative Site Occurring within 6 weeks of any spine procedure (initial or subsequent) at the index or 
adjacent level) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Implant (Total) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Breakage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Loosening 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Migration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Malposition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subsidence 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar Spinal Event Target Level 
 (Total) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spinous Process Bone Erosion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spinous Process Bone Reactive 
Change / Sclerosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
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Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Spinous Process Fracture 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Facet Joint Degenerative Changes 
(Weishaupt) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote)£ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar Spinal Event Adjacent 
Contiguous Level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar Spinal Event Adjacent 
Non-Contiguous Level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nonoperative Control Group Event 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nonunion (pseudarthrosis) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraoperative Events 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anatomic/Technical Difficulty 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar –Initial Surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
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Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Lumbar – Subsequent Surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Device Unable to be Implanted 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraoperative Device Revision 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dural Tear/Leakage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraoperative Vascular Injury 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anesthesia, Airway,Ventilation  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visceral Injury 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraoperative Neurologic Injury 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intraoperative hypotension 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood transfusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Excessive blood loss 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Major allergic reaction 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                             Perioperative Systemic Events (Occurring ≤ 6weeks of operation) 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deep vein thrombosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
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Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Pulmonary embolism 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Retrograde Ejaculation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anesthesia, Airway,Ventilation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac arrest/failure/arrhythmia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myocardial infarction 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dysphagia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dysphonia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gastrointestinal bleeding 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pneumonia 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pressure sores 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinary tract infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CSF leak/meningocele 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sepsis unrelated to operative site 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Post-Surgical Spinal Injections / Needle Based Procedures /Rhizotomies / Spinal Stimulators 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Epidural 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Nerve root block 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Facet Joint injection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medial branch block 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sacroiliac injection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Trigger point 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rhizotomies 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 98 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Spinal Stimulators 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incision-Related, Non-Infectious (Lumbar) 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Posterior  Lumbar 
Study Surgical Incision  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dehiscence 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematoma 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematoma Evacuation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CSF Leakage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Posterior Lumbar  Non-Study 
Incision (Specify AE type) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infection 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Superficial Wound – Posterior      
Lumbar Study Incision 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deep Wound – Posterior Lumbar   
Study Incision 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visceral / Organ space (Index level) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Superficial Wound – Posterior      
Lumbar Non-Study Incision 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deep Wound – Posterior Lumbar     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 99 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Non-Study Incision 
Visceral / Organ space (Non-Index 
Spinal level) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   Other (i.e., cellulitis, erythema) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subsequent Surgical Interventions (Lumbar) 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reoperation: Index level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reoperation: Adjacent Contiguous 
Level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reoperation: Index level and 
Adjacent Contiguous Level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reoperation: Adjacent Non-
Contiguous Level 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Neurological† 
Neurological 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total (Upper extremity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper Extremity – Sensory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 100 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Upper Extremity – Motor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper Extremity – Reflex 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total (Lower extremity) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity – Sensory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity – Motor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity – Reflex 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Spinal Cord / Cauda Equina      
Disturbance 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper extremity nerve   
compression (i.e. carpal tunnel) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjective*  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Non-specific or Other** 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pain Events 
Pain Events Considered as Spine-Related 
Cervical Spine/Upper Extremity  
Pain (Total) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cervical Pain (Cervical Region) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper Extremity Pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Combined Cervical and Upper   
Extremity Pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thoracic Pain (Thoracic Region) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 101 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Lumbar Spine/Lower Extremity 
Pain (Total) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low Back Pain (Lumbar Region) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity Pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Combined Low Back and Lower  
Extremity Pain 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (Non-Spinal) Pain 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper Extremity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Torso/Mediastinal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Headache 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pelvic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Musculoskeletal Events 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cervical 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thoracic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lumbar 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upper Extremity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lower Extremity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sacroiliac 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 102 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Systemic Events (Total, Includes Systemic Events Occurring Within 6 Weeks of Index Surgery) 
Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Respiratory 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiac 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gastrointestinal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infection (Systemic) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cancer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dermatologic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urogenital 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ear, Nose, Throat 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Endocrine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hepatobiliary 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunologic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Metabolism/Nutrition 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gynecologic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Opthalmologic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psychological 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical Procedure: Non-Spinal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wound Infection (other f1spinal 
region: thoracic, cervical) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wound Infection (non-spine related 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 103 of 117 
 
 
Surgery 
to 
Discharge 
Discharge 
to Week 6 
Week 6 
to Month 3 
Months 
3 to 6 
Months 
6 to 12 
Months 
12 to 18 
Months 
18 to 24 
Investigational 
group 
Control 
Group 
Adverse Event Category 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
I 
C 
#Subjects 
(% of xx) 
Total 
Events 
#Subjects 
(% of xx) 
Total 
Events 
incision) 
Incision-Related, Non-Infectious 
(other spinal region: thoracic, 
cervical) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Incision-Related, Non-Infectious 
(non-spine related incision) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Spinal Event Thoracic 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    Spinal Event Cervical 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other (please specify in footnote) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Totals 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
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Classification of Adverse Events by their seriousness and relationship to the 
investigational device shall be performed according to the following definitions.  
Seriousness of Adverse Event  
 Serious Adverse Event – an undesirable event that is fatal or life-threatening, 
or serious deterioration in the patient health that results in disabling 
(permanent impairment) or which necessitates prolonged hospitalization or 
medical or surgical intervention to prevent said life-threatening illness/injury 
or permanent impairment. Examples of serious adverse events are nerve root 
injury leading to significant and permanent paralysis, and vascular damage to 
major vessel.  
 Moderate Adverse Event - an undesirable event that does not fall into any of 
the serious adverse event definitions, and that may cause non-severe 
deterioration in the patient health (without significant permanent harm); 
moderate adverse event may require medical or minimal invasive surgical 
intervention or prolonged hospitalization. Examples of moderate adverse events 
are seroma or hematoma that mandate drainage, or dehiscence mandating 
revision of wound.       
 Minor Adverse Event – an undesirable event that did not result in any of the 
serious- or moderate adverse event outcomes, that is transient and does not 
lead to permanent disability or mandating prolonged hospitalization, invasive 
intervention, or prolonged medical treatment. Examples of minor adverse 
events are post-operative fever that resolved spontaneously, or wound problem 
that does not mandate drainage or surgical intervention.   
 
Device Relatedness 
An assessment regarding the causal relationship between the investigational device 
and an adverse event (device relatedness) should result in classifying the adverse 
event as Definitely Related-, Possibly Related-, or Unrelated to the investigational 
device, as hereby described. 
 Definitely Related - The adverse event is clearly related to the investigational 
device, and no alternative cause is present. Such events may be due to device 
malfunction or direct injury of the device to the surrounding tissue.  

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
CARBOCLEAR P_CLD 2492_US_IRBs_003_05/2017              CONFIDENTIAL          Page 105 of 117 
 
 
 Possibly Related - There is a reasonable possibility that the adverse event may 
have been caused by or is linked in a significant way to the investigational 
device, but an alternative cause is present. 
 Unrelated - The adverse event is clearly not related to the investigational 
device, and an alternative cause is present. Such events may be associated with 
the surgery and general anesthesia or hospitalization, e.g., not related to the 
anatomic surgical site.     
 
In addition, an independent Clinical Events Committee (CEC) will be established, to 
review all Adverse Events and determine the following:  
a) Appropriate category for Adverse Events;  
b) Severity, including whether or not the event should be classified as life-
threatening;  
c) Relationship to the device;  
d) Relationship to the procedure. 
The CEC will be composed of three members, US orthopedic surgeons, experienced 
in lumbar spinal fusion and pedicle screws fixation, who had conducted in the past 
similar clinical studies and similar adverse events evaluations. 
 
All Adverse Events shall be reported to the Sponsor at: Fax: +972-9-9548939; Tel: 
+972-9-9511511; E-mail: hila@carbo-fix.com. This shall be done as soon as possible 
and no later than 5 working days after the event was first discovered. In case of a 
verbal report, a written notification, using the relevant CRF (Adverse Events Report 
Form), shall be followed within 5 calendar days. 
Serious adverse events, serious adverse device effects, and device deficiencies that 
could have led to a serious adverse device effects should be reported to the Sponsor 
within 24 hours after knowledge to the Investigator or any study-related study center 
staff. Verbal report shall be followed by a detailed written notification within two 
calendar days, using the relevant form in the CRF.  
Language of the reports shall be English.  
 

                                                                                                                         
 
 
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The Sponsor is responsible for the classification of Adverse Events and ongoing 
safety evaluation of the clinical investigation, and shall review the Investigator's 
assessment of all Adverse Events and determine and document in writing their 
seriousness and relationship to the investigational device.  
In case of device deficiency, the Sponsor shall determine and document in writing 
whether it could have led to a serious adverse device effect. 
The Investigator shall supply the Sponsor, upon Sponsor's request, with any additional 
information related to the safety reporting of a particular event. 
 
The Sponsor shall report to the Institutional Review Board (IRB), or ensure the 
reporting by the Investigator, of serious adverse events, serious averse device effects, 
and device deficiencies that could have led to a serious adverse device effect, if 
required by national regulations or by the IRB/EC. Where required, the Sponsor is 
responsible for reporting such events to the relevant regulatory authorities. 
 
5.15 
INFORMED CONSENT 
Each subject enrolled into the study must give a written and signed informed consent 
to participate in the study, prior to entrance into the study.  
Each subject must be informed about the investigation, and must sign and date, prior to 
any procedure specific to the clinical study applied to him/her, an Informed Consent 
Form, acknowledging that participation is voluntary and that the follow-up visits are 
essential to complete data collection. The Investigator shall also sign and date the Form.   
The Investigator will carefully explain the research nature of the study to the subject, 
avoiding any coercion or undue influence on the subject to participate the study.  
A copy of the signed Informed Consent Form will be given to the subject; the 
Investigator shall retain an original copy.  
The IRB must approve the Informed Consent Form used. 
 
The Informed Consent materials are provided in Appendix E. 
 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
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5.16 
CASE REPORT FORMS 
The data reported on the Case Report Forms (CRF) shall be derived from source 
documents and be consistent with these source documents; any discrepancies shall be 
explained in writing.  
Source data is all information, original records of clinical findings, observations, or 
other activities in a clinical study necessary for the reconstruction and evaluation of the 
study. Source data are contained in source documents.  
Examples of these original documents and data records include hospital records, 
clinical and office charts, laboratory notes, memoranda, patients’ evaluation checklists, 
recording media such as DVD, x-rays, patient files, and records kept at the laboratories. 
The Investigator shall assure the accuracy, completeness, legibility and timeliness of the 
data reported to the Sponsor on the CRFs and in all required reports. Where copies of 
the original source document as well as printouts of original electronic source 
documents are retained, these shall be signed and dated by a member of the 
investigation site team with a statement that it is a true reproduction of the original 
source document. 
All data requested on the CRFs must be recorded. Missing data shall be explained. The 
CRFs shall be filled in English, and signed and dated by the Investigator. Any change 
or correction to data reported on a CRF shall be dated, initialed and explained if 
necessary, and shall not obscure the original entry. 
 
The Case Report Forms (as well the Patient Questionnaires) are provided in 
Appendix F. 
 
5.17 
CONFIDENTIALITY  
The privacy of each subject participating in the study and confidentiality of his/her 
information shall be preserved. The patient’s full name will be removed from any 
study document to maintain confidentiality. Subject number and initials will identify 
patients. Data shall be secured against unauthorized access.  
 

                                                                                                                         
 
 
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5.18 
MONITORING 
Monitoring of the study will be performed according to the Sponsor’s approved 
monitoring procedures.  
The Sponsor shall appoint a monitor to oversee the clinical study. The monitor shall 
be qualified by training and experience to monitor clinical studies, and shall be 
knowledgeable on the use of the investigational device, as well as the relevant 
regulation and requirements, the investigational plan, and the informed consent 
process. Training of the monitoring shall be documented in the Sponsor's files. The 
monitor may be an employee of the Sponsor or an independent contractor consultant.  
The Sponsor, together with the monitor, will set a specific plan for the conduction of 
monitoring activities and schedules. This plan may be modified during study 
progression as deemed necessary by the Sponsor and monitor, based on the monitor 
periodic site visits/communication reports. 
 
Prior to initiation of the study, the monitor will visit or otherwise contact each site of 
the clinical investigation and will assure that the Investigator: 
1. 
has adequate qualifications; 
2. 
understands the investigational status of the system and the investigational 
plan; 
3. 
understands and accepts the obligations related with conducting the clinical 
investigation and the requirements set by the applicable regulations; 
4. 
understands and accepts the obligation to obtain IRB approval prior to 
initiation of the study and the obligation to notify the Sponsor of any changes 
to that approval status; 
5. 
signed the Investigator Agreement and forwarded a signed copy to the 
Sponsor; 
6. 
understands and accepts the obligation to obtain an informed consent 
according to the relevant regulations;  
7. 
has the adequate number of subjects suitable for the project, adequate 
facilities and resources, and sufficient time to carry the responsibilities of an 
investigator; and 
8. 
was (with his/her team) trained for the use of the investigational device; 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
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9. 
understands the importance of a timely report of any adverse events. 
 
The monitor will be responsible for initiating the study and verifying that all the 
protocol and regulatory authority requirements are met prior to the initiation of the 
study (e.g., the study protocol and other study documents were received and are 
understood to the investigator and his/her staff; the investigator and his/her team were 
trained for the use of the investigational device and are familiar with the investigator 
responsibilities, etc.).  
Upon site initiation, a log shall be established identifying names, initials, signatures, 
functions, and designated authorities for the investigator and members of the 
investigation site team. In addition, a log for patient identification shall be issued.  
The findings of the study initiation visit shall be documented 
 
During the course of the investigation, the monitor shall conduct periodic monitoring 
visits, and where applicable discussions, to the investigational sites, according to 
predetermined schedule or as required. During those visits, the study monitor shall 
audit the site and shall verify that: 
1. 
the facilities are still acceptable for the study; 
2. 
the 
study 
Protocol/Investigational 
Plan, 
requirements 
of 
relevant 
International Standards, regulations and regulatory authorities (e.g., FDA), 
any condition imposed by IRB, and the Investigator Agreement, are being 
followed; 
3. 
any Protocol changes have been reported to the Sponsor and the IRB, and 
have been approved by the IRB, and, where applicable, other regulatory 
authorities; 
4. 
accurate, complete and current records are maintained and are consistent 
with source documents; 
5. 
special care should be taken to verify that the Informed Consent Forms are 
completed and signed accurately (i.e., signed and dated informed consent 
forms have been obtained at the point of enrolment or before any clinical-
investigation-related procedures were undertaken), and that adverse events 
are carefully monitored and reported; 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
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6. 
reports to the Sponsor and to the IRB are accurate, complete and made in 
timely manner; 
7. 
appropriate corrections, additions or deletions are made to the CRFs, dated, 
explained if necessary, and initialed by the Investigator (or by his/her 
authorized designee); the monitor shall not make corrections, additions or 
deletions to the CRFs; 
8. 
the Investigator has not delegated activities to other staff which were not 
specified and authorized previously; 
9. 
the investigational device is being used according to the protocol and 
Instructions for Use and that, where modifications are required to the device 
or its method of use, these are reported to the Sponsor; 
10. 
storage and investigational device accountability are correct and the 
traceability process is being followed;  
11. 
the investigator continues to have access to an adequate number of subjects 
and investigational devices; 
12. 
the investigator and investigation site team are informed and knowledgeable 
of all relevant document updates concerning the clinical investigation;  
13. 
any corrective and preventive actions, as needed, have been implemented and 
are effective. 
During the audit, study monitor may request study records, including source 
documents (individual subjects' records) for inspection and copying, and will compare 
them to the contents of reports made to the Sponsor by the Investigator to assure 
accuracy and completeness of the data. Any deficiencies noted will be corrected on 
site, if possible, according to correction instructions and adding the correct 
information. The correction shall be signed and dated by the Investigator. The finding 
of deficiencies may call for a review of a larger number of files or to rescheduling of 
the monitoring visits. Such decisions and the rationale for them will be recorded on 
the report made by the monitor to the Sponsor.  
In general, the said comparison will ensure that: 
i. 
the information recorded in the Investigator’s report to the Sponsor is 
complete, accurate and legible; 
ii. 
there are no omission of data elements in the reports; 

                                                                                                                         
 
 
                                                                                                                            CARBOCLEAR PEDICLE SCREW SYSTEM  
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iii. 
missing visits and data elements are noted as such in the reports; 
iv. 
subjects failing to complete the study and the reason for that are documented 
in the reports; 
v. 
informed consent is documented in accordance with the relevant regulations. 
 
The Investigator guarantees direct access to the study files, patient CRFs, and patient 
medical records, to staff of the Sponsor/monitor.  
 
The last monitoring visit to the site shall be the Site Closure/Study Termination Visit, 
during which the monitor shall verify, in addition to all the above, that the 
Investigator records are complete, all documents needed for the Sponsor's files are 
retrieved, and previously identified issues have been resolved. In addition, the monitor 
shall verify that the Investigator returned all the devices to the Sponsor, according to 
the Sponsor instructions, unless this action would jeopardize the rights, safety or 
welfare of the subjects.  
 
The findings of the study periodic and last monitoring visits shall be documented. 
All monitoring activities shall be forward in a written report to the Sponsor. A copy of 
the monitoring report or a summary of key findings shall be shared with the 
Investigator in writing. The records will include, at a minimum, the following 
information: 
1. 
date of the visit; 
2. 
name of the monitor; 
3. 
Investigator and site visited details, and of any other staff members present at 
the visit; 
4. 
a summary of the findings, conclusions, and any actions taken to correct any 
deficiencies noted during the visit. 
 
The monitor shall document and maintain a copy of all the records and reports of 
each visit/audit or other contact/communication with the site and Sponsor during the 
investigation and for a period of 2 years after the latter of the following: (i) the date 
on which the investigation is terminated or completed; or (ii) the date that the records 

                                                                                                                         
 
 
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are no longer required to support a regulatory notification to the authorities for the 
purpose of receiving a marketing clearance for the system in question. 
 
Adverse events resulting from malfunction of the Investigational Device, or any other 
clinical complications, should be reported to the Sponsor/study monitor as described 
above (see Section 5.14.4.2). 
In case of any unanticipated adverse device effect, the Sponsor shall immediately 
conduct an evaluation.  
If suspicion of an unacceptable risk to subjects arises during the clinical investigation, 
or when so instructed by the IRB or regulatory authorities, the Sponsor shall suspend 
the clinical investigation while the risk is assessed.  
The Sponsor shall terminate the clinical investigation if an unacceptable risk is 
confirmed (e.g., in case the sponsor determines that an unanticipated adverse device 
effect presents an unreasonable risk to subjects). The termination will occur within 5 
working days after the decision to terminate the study is taken and no later than 15 
working days after first becoming aware of the adverse event. If the suspension or 
premature termination was in the interest of safety, the Sponsor shall inform all other 
investigators. 
If resumption of the suspended study is desired – the Sponsor shall notify the 
investigator and the IRB (and if relevant – the regulatory authority) and provides them 
with the rational and supporting data. Study resumption shall be only following a 
written approval of the IRB. In the USA, resumption of terminated study is subjected 
to the regulation of CFR 21 part 812.46(c).   
 
The monitor shall immediately (and no later than 5 days following the discovery of 
such an occurrence) notify the Sponsor of any conditions of non-compliance with the 
signed Agreement, Protocol, Investigational Plan, conditions of IRB, FDA and/or 
other regulatory authority approval and/or regulations. In case compliance cannot be 
secured, the Sponsor will discontinue shipments of the device to the non-complying 
investigator and terminate its participation in the investigation. The Sponsor shall also 
require such an Investigator to return the devices, unless this action would jeopardize 
the rights, safety, or welfare of a subject. 

                                                                                                                         
 
 
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5.19 
OPERATIONAL ISSUES 
5.19.1 TRAINING 
Investigators should be fully experienced with the use of pedicle screw systems and 
interbody fusion devices, and the required specialized spinal surgery techniques.  
Training of the investigating team regarding the investigational device and the study 
Protocol will be provided by the Sponsor personnel or its authorized representative(s) 
prior to commencing any study-related procedure.  
In particular, training of the Investigator will include a lecture and demonstration 
(possibly electronically), as well as simulation of the use of the system in sawbones, 
according to the Training Protocol (Attachment D). Training, and Investigator 
competency with the device and compliance with training, will be documented.  
 
5.19.2 SUPPLY AND STORAGE (ACCOUNTABILITY) 
The Sponsor will supply the CarboClear System (implants and surgical instruments), 
for the performance of the procedures within the scope of this study, for as long as the 
study is carried. 
The CarboClear System shall be used only in the clinical investigation and according 
to this Protocol.  
The Sponsor shall keep records to document the physical location of all 
investigational devices to the investigation sites until return or disposal.  
All investigational devices received and used by the Investigator will be inventoried 
and accounted for throughout the study. The devices will be stored in a secure area 
with restricted access, separate from other medical devices. When instructed by the 
Sponsor, the Investigator will return any remaining devices to the Sponsor. The 
Investigator will not supply the investigational device to any person except those 
designated by him/her as co-investigator(s). If a device is explanted from a patient for 
any reason, it should be returned to the Sponsor following instructions provided by 
the Sponsor and/or the study monitor. 
The Investigator shall keep records documenting the receipt, use, return and disposal 
of the investigational devices, which shall include the following details: 
1. 
Date of receipt; 

                                                                                                                         
 
 
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2. 
Identification of each investigational device (e.g., lot number); 
3. 
Date of use; 
4. 
Subject identification; 
5. 
Date of return of unused, expired or malfunctioning investigational devices, 
if applicable. 
6. 
Date of investigational device disposal, if applicable. 
 
5.19.3 TRACEABILITY OF DEVICES AND DOCUMENTS 
Complete traceability of all devices will be maintained during the study. Records will 
include raw materials, manufacturing and inspection data, as well as implantation 
data. 
All documents and data shall be produced and maintained in a way that assures 
control and traceability. All documents, and subsequent versions, related to the 
clinical investigation shall be identifiable, traceable and appropriately stored to 
provide a complete history of the clinical investigation. 
Each device shall be assigned with a lot number. The Sponsor will be responsible for 
product delivery, monitoring (CRF, etc.) and traceability records.  
The investigational site shall maintain a log of all the subjects enrolled in the clinical 
investigation, assigning an identification code linked to their name. The Investigator 
will also maintain product inventory with traceability records and subject records.  
 
5.19.4 RECORD RETENTION 
Records related to the clinical study are subject to inspection by regulatory authorities 
and must be retained by the Sponsor and Investigator for a period as per regulations. The 
files may be discarded only upon notification from Sponsor.  
 
The Investigator is responsible for retention (and where applicable, for the 
preparation, review and/or signing) of the following records: 
 All correspondence, which pertain to the investigation; 
 Device use/disposition and accountability records (as detailed above); 
 Subject's case history records, including: 

                                                                                                                         
 
 
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a. Signed Informed Consent Form;  
b. All Protocol required evidences/observations; 
c. Observations of adverse events; 
d. Medical history; 
e. Documentation of the dates and reasons for any deviation from Protocol; 
f. Case Report Forms (CRFs): 
g. Patient Questionnaires. 
 
5.19.5 AMENDMENTS 
The Protocol, CRFs, Informed Consent Form and other subject information, or other 
clinical investigation documents, may be amended as needed throughout the clinical 
investigation, and a justification statement shall be included with each amended 
section of a document. The version number and date of amendments shall be 
documented.  
 
Proposed amendments to the Protocol shall be agreed upon between the Sponsor and 
Principle Investigator, and the Sponsor shall incorporate the amendment into the 
document. The amendments to the Protocol and the subject’s Informed Consent Form 
shall be notified to the IRB by the Sponsor, or approved by the IRB (and regulatory 
authorities, if required).  
Non-substantial changes that do not affect the rights, safety and well-being of human 
subjects, or that are not related to the clinical investigation objectives or endpoints, 
should be simply notified to the IRB.  
 
5.19.6 DEVIATIONS FROM PROTOCOL 
The Investigator is not allowed to deviate from the Protocol, except as specified 
below. 
Request for deviation from Protocol shall be agreed between the Sponsor and 
Investigator and communicate to the IRB by the Sponsor.  
Under emergency circumstances, deviations from the Protocol to protect the rights, 
safety and well-being of human subjects may proceed without prior approval of the 

                                                                                                                         
 
 
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Sponsor and the IRB. Such deviations shall be documented by the Investigator and 
reported to the Sponsor as soon as possible and to the IRB. 
 
5.19.7 PUBLICATION 
The results of this study may be submitted for publication. In case the study results 
are published, the participating subjects' identity will not be disclosed.  
The ownership of the data shall, at all times, be held by the Sponsor.  
The Sponsor reserves the right to include the report of this clinical investigation in 
any regulatory documentation or submission or in any informational materials 
prepared for the medical profession.  
Upon approval by the Sponsor, Investigators are permitted to present the data at 
symposia, professional meetings, and to publish in journals, theses or dissertations 
methods and results of the study. Investigators agree to delay presentation or 
publication of study results until agreed to by all contributing centers, and by the 
Sponsor. 
 
 
 
 
 

                                                                                                                         
 
 
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APPENDICES 
Appendix A – Surgical Technique 
Appendix B – Control Table 
Appendix C – Training Protocol 
Appendix D – Radiographic Protocol 
Appendix E – Patient Informed Consent 
Appendix F – CRFs and Patients Questionnaires