A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE in Adults With Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
Phase: NA
Conditions: Fused Vertebrae, Ankylosing Spondylitis, Sagittal Deformities, Thoracolumbar Kyphosis
Sponsor: Abyrx, Inc.

A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of 
MONTAGE in Adults with Spinal Deformity Undergoing Pedicle Subtraction 
Osteotomy 
PROTOCOL 
NUMBER: 
ABYRX- MONTAGE 001-2017 
PRINCIPAL 
INVESTIGATOR(S): 
William Lavelle, MD 
INDICATION: 
Hemostasis after Pedicle Subtraction Osteotomy 
for Adult Spinal Deformity 
PRODUCT: 
MONTAGE 
DEVELOPMENT 
PHASE: 
Phase 4 – Post-market 
SPONSOR: 
Abryx, Inc. 
1 Bridge Street, Suite 121, 
Irvington, NY  10533 
MEDICAL 
MONITOR: 
Jan Lessem, M.D., Ph.D., FACC 
Consultant Medical Officer 
ABYRX 
Mobile: 857-891-6525 
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20182341
IRB Approved at the 
Protocol Level 
Jan 08, 2019

Table of Contents 
Protocol Approval ....................................................................................................................................... 7 
Investigator Agreement .............................................................................................................................. 7 
1.
INTRODUCTION .................................................................................................................................. 8 
1.1 
STATEMENT OF INTENT ........................................................................................................... 8 
1.2    
TITLE ........................................................................................................................................... 8 
1.3    
BACKGROUND INFORMATION ................................................................................................ 8 
1.4    
OBJECTIVES .............................................................................................................................. 9 
2.1    
DESCRIPTION OF INVESTIGATIONAL PRODUCT UNDER TEST ......................................... 9 
2.2 
PACKAGING AND LABELING .................................................................................................. 10 
2.3 
METHOD OF DISTRIBUTION .................................................................................................. 10 
2.4 
ACCOUNTABILITY ................................................................................................................... 10 
The investigator or designated individual will maintain inventories that will detail receipt, use, 
return and collection of Montage trial supplies by the company.  The use inventory log will be 
used to document which products (batch, expiry, and quantity) were used on which subjects for 
traceability.................................................................................................................................................. 10 
3.
TRIAL SUBJECT POPULATION ....................................................................................................... 10 
3.1 
NUMBER OF SUBJECTS ......................................................................................................... 10 
3.2 
SUBJECT SOURCES ............................................................................................................... 10 
3.3 
SELECTION CRITERIA ............................................................................................................ 10 
3.3.1 
Inclusion Criteria ............................................................................................................. 10 
3.3.2 
Exclusion Criteria ............................................................................................................ 11 
3.4 
WITHDRAWAL .......................................................................................................................... 12 
4.
TRIAL DESIGN AND METHODOLOGY ............................................................................................ 12 
4.1   
TRIAL DESIGN .......................................................................................................................... 12 
4.2.1   
Screening and Pre-Treatment Regimen ........................................................................ 13 
4.2.1.1
Visit #1:  Screening Evaluation and Enrollment (Week -2) ........................................................................... 13
4.2.2 
Randomization ........................................................................................................................... 14 
4.2.2.1
Visit #2:  Randomization ................................................................................. Error! Bookmark not defined.
4.2.3 
Treatment ......................................................................................................................... 14 
4.2.3.1
Visit #3:  Treatment Phase (Week 0) ........................................................................................................... 14
4.2.3.2
Visit #4:  Follow-up Visit (Week 2) ............................................................................................................... 14
4.2.3.3  Visit #5:  Follow-up Visit (Week 6) ....................................................................................................................... 14
4.2.3.4  Visit #6:  Follow-up Visit (Week 12) ..................................................................................................................... 14
4.2.3.5
Visit #7:  Follow-up Visit (Week 24) ............................................................................................................. 14
4.2.3.6  Visit #8: Follow-up visit (Week 52) ....................................................................................................................... 15
5.
ADVERSE EVENTS (DEFINITIONS AND REPORTING) ................................................................. 15 
5.1 
ADVERSE EVENT .................................................................................................................... 15 
5.1.1 
Reporting of Adverse Events ......................................................................................... 15 
5.1.2 
Subject Follow-up ........................................................................................................... 16 
5.2 
SERIOUS ADVERSE EVENT ................................................................................................... 16 
5.2.1 
Reporting Serious Adverse Events ............................................................................... 17 
5.3 
UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) ........................................................ 17 
5.3.1 
Reporting UADEs ............................................................................................................ 17 
6.
STATISTICAL DESIGN...................................................................................................................... 17 
6.1 
DESIGN ..................................................................................................................................... 18 
6.2  
SAMPLE SIZE ........................................................................................................................... 18 
6.3 
ANALYSIS PLAN ....................................................................................................................... 18 
6.3.1 
Subject Analysis Sets ..................................................................................................... 18 
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6.3.2 
Secondary Variables and Analyses ............................................................................... 19 
6.3.3 
Safety ................................................................................................................................ 19 
6.3.4 
Other Data Summaries .................................................................................................... 19 
7.
ADDITIONAL INFORMATION ........................................................................................................... 19 
7.1 
USE OF ADDITIONAL MEDICAL SERVICES .......................................................................... 19 
7.2 
SOURCE DATA VERIFICATION (SDV) ................................................................................... 19 
7.3 
TRIAL MONITORING ................................................................................................................ 19 
7.4 
USE OF TRIAL FINDINGS ........................................................................................................ 20 
8.
ETHICAL AND LEGAL ISSUES ........................................................................................................ 20 
8.1 
GOOD CLINICAL PRACTICES (GCP) ..................................................................................... 20 
8.2 
APPROVAL OF PROTOCOL .................................................................................................... 20 
8.3 
CONFIDENTIALITY ................................................................................................................... 20 
8.4 
INSURANCE/FINANCIAL.......................................................................................................... 20 
8.5 
SUBJECT CONSENT ................................................................................................................ 20 
9.
REFERENCES ................................................................................................................................... 22 
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List of Abbreviations 
AE 
Adverse Event 
cm 
Centimeter 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
FDA 
U.S. Food & Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
in 
Inch 
IRB 
Institutional Review Board 
ITT 
Intention-to-Treat 
ODIv2.1a 
Oswestry Disability Index version 2.1a 
QoL 
Quality-of-Life 
SAE 
Serious Adverse Event 
SRS-22 
Scoliosis Research Society -22 Outcomes 
UADE 
Unexpected Adverse Device Effect 
VAS 
Visual Analog Scale back and leg pain
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SUMMARY 
Title: 
A Prospective, Multicenter, Randomized, Controlled 
Clinical Investigation of MONTAGE in Adults with 
Spinal Deformity undergoing Pedicle Subtraction 
Osteotomy 
Short Title: 
MONTAGE in PSO for Adult Spinal deformity 
Protocol Number: 
Montage 001-2017 
Phase: 
Phase 4-postmarketing 
Methodology: 
Prospective, randomized, open, controlled study 
Study Duration: 
2 years from entry of last subject 
Follow-up: 
2 years 
Study Centers: 
Multicenter study with up to 4-6 centers 
Objectives: 
Primary: To assess the safety and effectiveness of 
MONTAGE in reducing post-operative blood loss  
Secondary: To assess the PSO stability 
Number of Subjects: 
50 subjects 
Diagnosis and Main Inclusion Criteria: 
1. Presence of spinal deformity requiring a PSO
2. Patients aged 18-80 and
3. Non-smokers (must have quit smoking 6 months
prior to surgery) and current smokers
Study Product, Dose, Regimen: 
After surgically creating the wedged PSO defect, prior 
to closure of the osteotomy, patients will be 
randomized 1:1 to receive either MONTAGE applied to 
the cut surfaces for the osteotomy site or no hemostatic 
material. 
Duration of Administration: 
1 application during surgery 
Reference Therapy: 
Standard of care – no bone hemostat. 
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End-points and Statistical Methodology: 
Efficacy Endpoint: 
Safety Endpoints: 
The primary efficacy outcome variable for the study is 
the amount of post-operative bleeding compared 
between patients randomized 1:1 to MONTAGE or 
standard of care (no bone hemostat).  Blood loss will 
be measured indirectly by formulae that provide an 
estimate through changes in hematocrit.  A 2-sided “t” 
test will be used for the analysis. 
Consistent with the standard of care, successful 
reconstruction of the osteotomy site requires 
observation of the residual angle of the osteotomy and 
any gap that may be present.  In order to demonstrate 
that the use of Montage does not negatively impact the 
desired outcome, any residual gap will be measured in 
millimeters and compared between the groups. This 
will be done by including a CT scan performed at 1-
year post surger A 2-sided “t” test will be used for the 
analysis. 
NRS back pain and NRS leg pain, SRS-22 and 
Oswestry Disability Index (ODIv2.1a) will be compared 
between the two groups and also reported as 
secondary outcome scores. Descriptive statistics will 
be reported.  
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PROTOCOL APPROVAL  
 
 
Date ................................. 
,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 
 
 ........................................ 
William Lavalle, MD 
 
 
 ........................................ 
…………………………………………………… 
 
Date 
Jan Lessem, MD, Ph.D 
 
 
Consultant Medical Officer  
 
ABYRX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
INVESTIGATOR AGREEMENT  
 
 
The signing of this protocol by the Investigator signifies that the contents have been laid down in full 
agreement and that the trial will be conducted according Good Clinical Practice and to the procedures 
described. 
 
 
 
 
 
 
 ........................................ 
 ....................................................................... 
 
Date 
<Investigator> 
 
 
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1.
INTRODUCTION
1.1 
STATEMENT OF INTENT 
The design, conduct and reporting of this trial shall be undertaken in compliance with the protocol, ICH/GCP 
and all appropriate regulatory requirements. 
1.2    
TITLE 
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE in Adults 
with Spinal Deformity undergoing Pedicle Subtraction Osteotomy  
1.3     
BACKGROUND INFORMATION 
PEDICLE SUBTRACTION OSTEOTOMY - ASSOCIATED BLOOD LOSS 
Pedicle Subtraction osteotomy (PSO) is a surgical option for treating several spinal deformities. It has been 
utilized in alignment disorders of the fused spine, in the lumbar spine to treat large sagittal deformities and 
in patients with ankylosing spondylitis with thoracolumbar kyphotic deformity (1). 
PSO is a procedure most commonly performed in the lumbar and thoracic spinal regions. PSO is often 
avoided in the distal lumbar spine because the risk of the neurologic injury is greater and fewer fixation 
points are available. It has been suggested that some of the ideal candidates for PSO are those patients 
with a substantial sagittal imbalance  > 10 to 12 cm, with a sharp angular kyphosis and patients who have 
circumferential fusion along multiple segments. For most patients with ankylosing spondylitis, PSO could 
be the treatment of choice.  The procedure involves surgical excision of a wedge of bone from the posterior 
spine (osteotomy).  The two cut edges are then drawn together by a system of screws and rods designed 
to apply compression and thus reduce the unnatural forward curvature of the spine.   
PSO typically results in substantial loss of blood (as much as 2L) with a significant portion of the loss likely 
occurring at the osteotomy surfaces post-surgically.  Blood loss-associated morbidities can be direct, 
including hypotension, organ damage (particularly cardiac, pulmonary, renal) and coagulopathy.  Excessive 
blood loss also may require allogeneic blood transfusion, which may further result in acute lung injury, 
hypersensitivity reactions, infections, and immune suppression.  Another concern with regard to post-
operative bleeding in spinal surgery is the risk of spinal epidural hematoma formation, which might lead to 
spinal cord or cauda equina compression.  Therefore, the control of peri-operative blood loss is considered 
a critical issue by spine surgeons (2,3,5). 
A variety of methods have been proposed for the reduction of blood loss during or immediately after spine 
surgery, including preoperative use of erythropoietin, autologous blood, cell salvage, intra-operative 
controlled hypotension, and the use of anti-fibrinolytic drugs (6).  Bone hemostats have traditionally not 
been part of the standard of care to promote hemostasis probably because most available options (e.g., 
bone wax) are nonabsorbable and thus might interfere with fusion at the osteotomy site. 
MONTAGE 
MONTAGE is a settable (hardening) bioabsorbable polymer and hydroxyapatite/beta tricalcium phosphate 
based putty, used in the control of bleeding from bone during spine, orthopedic, craniomaxillofacial, thoracic 
and other surgical procedures.  
It is easy to manipulate and typically results in immediate and complete cessation of bleeding at the bony 
defect. The putty hardens within minutes after application, remaining secure in place, without being 
dislodged or dissolved during the early stages of bone formation.  In animal studies, the use of MONTAGE 
has not been shown to interfere with bone healing or fusion (7). 
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MONTAGE putty was implanted in rabbit diaphyseal femoral defects (N=12) and each defect was evaluated 
after 4 weeks by histopathology (8). The microscopic evaluation demonstrated no significant signs of 
inflammation or fibrosis, while there was indication that new bone formation occurred. MONTAGE is fully 
absorbed within approximately 1 year and is replaced with endogenous bone. 
 
MONTAGE settable putty is FDA cleared as a bone hemostat in skeletal surgical procedures.  
 
 
1.4     
OBJECTIVES 
 
The primary objective of this study is to evaluate the difference in postoperative bleeding between two study 
groups, FDA cleared MONTAGE and standard of care (no bone hemostat), and the extent to which any 
transfusion is needed and blood loss is measured through drop in hematocrit (HCT), as well as wound drain 
output, if utilized.  As an exploratory evaluation of the primary endpoints a calculation will be made of blood 
loss for the first 7 days following surgical procedure as assessed by a multivariate combination of these 
measures of blood loss. 
 
The secondary objective is the stability of the construct, as measured by whether the correction has 
maintained stability at 1-year and 2-years post surgery.  Each incidence of instability will be categorized as 
belonging to one of the following groups: 1) hardware malplacement, 2) loosening or dislodegment, 3) 
nonunion or nonfusion with hardware fracture 4) nonunion or nonfusion without hardware fracture and 5) 
perihardware fracture.   
 
Each osteotomy site will be assessed using X-rays and with computed tomography (CT) scans – performed 
at 12 months post surgery. Failure of fusion will be determined to be present if an area of bone apposition 
lucency greater than 2mm in thickness is present. 
 
Secondary objectives will also include:  
 
- The formation of new bone, as measured by CT scans at 1-year post surgery,  
 
- Evaluation of Visual Analog Scale (VAS) back and leg pain, Oswestry Disability Index (ODIv2.1a), and 
SRS-22 scores, which will be recorded during the study and compared between the two groups.  
 
- Evaluation of work status. 
 
-Antifibrinolytics use and type will be recorded during the study and compared between the two groups 
 
 
 
2.     
INVESTIGATIONAL PRODUCT/TREATMENT 
 
2.1     
DESCRIPTION OF INVESTIGATIONAL PRODUCT UNDER TEST 
 
MONTAGE is a settable (hardening) bioabsorbable polymer and hydroxyapatite/beta tricalcium phosphate 
based putty, used in the control of bleeding from bone during spine, orthopedic, craniomaxillofacial, thoracic 
and other surgical procedures, and has been FDA cleared.  
 
It is easy to manipulate and in all instances, as reported in preclinical studies, resulted in immediate and 
complete cessation of defect bleeding. The putty hardens within minutes after application, remaining secure 
in place, without being dislodged or dissolved. 
 
In rabbit diaphyseal femoral defects (N=12), MONTAGE putty was implanted; and after 4 weeks each defect 
was evaluated by histopathology. The microscopic evaluation demonstrated no significant signs of 
inflammation or fibrosis, while there was indication that new bone formation occurred. 
 
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MONTAGE has been used in many clinical settings, including during spinal and sternotomy procedures. 
Long-term follow-up in various settings has not demonstrated any adverse events of significance. (9, 10, 
11, 12). 
2.2 
PACKAGING AND LABELING 
MONTAGE will be supplied terminally sterilized in individual packaged units of 5cc (10grams). MONTAGE 
should be stored at room temperature. 
2.3 
METHOD OF DISTRIBUTION 
Delivery of all study materials (e.g. product, CRFs, etc.) to the study centers will be arranged by the 
Sponsor’s Clinical Research Associates (CRA).   
2.4 
ACCOUNTABILITY 
The investigator or designated individual will maintain inventories that will detail receipt, use, return and 
collection of Montage trial supplies by the company.  The use inventory log will be used to document 
which products (batch, expiry, and quantity) were used on which subjects for traceability. 
3.
TRIAL SUBJECT POPULATION
3.1 
NUMBER OF SUBJECTS 
A multicenter study will be undertaken in the US, with up to 4-6 centers contributing 50 patients (maximum 
of 20 patients per center). A sample size of 25 randomly assigned patients per study group (50 subjects in 
total) was calculated to detect a clinically significant treatment effect of MONTAGE (90% power; alpha = 
0.05, 2-sided; 10% lost-to-follow up). This calculation was performed with the assumption that subjects 
within the control group lose on average 1,500 mL (+/- 500mL) of blood postoperatively while subjects 
within the treatment group will lose 1,000 mL of blood postoperatively. 
3.2 
SUBJECT SOURCES 
Adult subjects referred to hospital or community-based clinics for treatment of spinal deformity will be 
eligible for the study. 
3.3  
SELECTION CRITERIA 
The following criteria must be met before a subject is recruited to the trial: 
3.3.1 
Inclusion Criteria 
1.
Subject is at least 18 years old, and not more than 80 years old.
2.
Presence of spinal deformity requiring a PSO at a single site level, such as for patients with
thoracolumbar kyphotic deformity, sagittal imbalance, and spinal global malalignment.
3.
Non-smokers (have proven to quit smoking for at least 6 months prior to surgery) and current
smokers
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3. 
Female subjects of childbearing potential must be willing to use acceptable methods of 
contraception (birth control pills, barriers, or abstinence).  A pregnancy test at the Week 0 visit must 
be administered, and must be negative, for inclusion into the study. 
 
4. 
Subject understands and is willing to participate in the clinical study and can comply with required 
visits and the follow-up regimen. 
 
5. 
Subject has read and signed the Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved Informed Consent Form before screening procedures are undertaken. 
 
 
 
 
3.3.2  
Exclusion Criteria 
 
1. 
Subjects whose spinal deformity is deemed by the investigator to be of such severity that a possible 
surgical intervention would be either harmful or not warranted. 
 
2. 
Subjects with morbid obesity (i.e. a Body Mass Index [BMI] ≥ 40). 
 
3. 
Subjects who have a known allergy to the components of MONTAGE. 
 
4. 
Subjects who are non-mobile (i.e. not ambulatory, or have significant impairment of their mobility 
making them completely bedridden).  
 
5. 
Subjects who, in the opinion of the investigator, show evidence of infection, cellulitis, and/or 
osteomyelitis. 
 
6. 
Subjects with abnormally low platelets, abnormal coagulation parameters, or with documented 
bleeding disorders, including a prior history of excessive bleeding during surgery. 
 
6. 
Subjects with a history of a malignancy, not in remission for five years or more, or a newly 
diagnosed  malignancy, treated with cytotoxic therapies or radiation therapy. 
 
7. 
Subjects on any investigational drug(s) within 30 days preceding randomization (i.e. Week 0); or 
subject or physician anticipates use of any of these therapies by the subject during the course of 
the study. 
 
8. 
Subjects with:  
 
 (ii) 
Alcohol abuse as recorded by an average daily intake of > 4 units in females, > 5 units in 
males (i.e. 1 oz. of spirit, glass of wine, or can of beer per unit). 
 
(iii) 
Drug abuse as evidenced by the subject’s use of illegal drugs or prescription drugs that 
have not been prescribed for him/her. 
 
9. 
Subjects with one or more medical conditions, as determined by medical history, including renal, 
hepatic, hematologic, active auto-immune or immune diseases that, in the opinion of the 
Investigator, would make the subject an inappropriate candidate for this study.  
 
 
10. 
Subjects with a history of osteoporosis, as defined by imaging, or on medication for osteoporosis 
or documented fracture of fragility (Hip fracture, osteoporotic compression fracture, distal radius 
fracture).  If there are any concerns these may be arbitrated by the study PI.  
 
11. 
Subject has previously participated in any MONTAGE trial. 
 
12. 
Subjects who are unable to understand the aims and objectives of the trial and/or unwilling to return 
for the follow-up examinations.. 
 
 
 
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3.4 
WITHDRAWAL 
Subjects may drop out or be withdrawn at their own request.  Although subjects need not give a reason for 
requesting withdrawal from the trial, the investigator should make a reasonable effort to ascertain the 
reason(s), while fully respecting the subject's rights.   
4.
TRIAL DESIGN AND METHODOLOGY
4.1    
TRIAL DESIGN 
This study will be an open, prospective, multicenter, randomized, and controlled study to evaluate the 
effects of MONTAGE® on blood loss and maintenance of the PSO corrective surgical procedure. 
Patients will be randomized to receive either standard of care (no bone hemostat) or MONTAGE. Within 
each study group, patients will be stratified according to their smoking status (non-smokers versus current 
smokers).  
4.1.1 
PRIMARY OBJECTIVE 
To assess the effectiveness of MONTAGE in reducing blood loss in the first week after surgery.  A formula 
will be used to calculate blood loss during the post-surgical period up until day 7 or hospital discharge 
(whichever comes first). The following formula from the Harms Study Group, shown at day 3 as an example, 
will be used and comparisons of blood loss between the two groups will be calculated. 
4.1.2 SAFETY OBJECTIVES 
Safety objectives will include: 
- Evaluation of the repaired osteotomy by measuring displacement of the edges of the bone under
compression. The angular measurement is the angle between the superior endplate of the vertebral body
below the PSO and the inferior endplate of the vertebral body above the PSO. Consistent with the
standard of care, successful reconstruction of the osteotomy site requires observation of the residual
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angle of the osteotomy and any gap that may be present.  In order to demonstrate that the use of 
Montage does not negatively impact the desired outcome, any residual gap will be measured in 
millimeters and compared between the groups. This will be done by including a CT scan performed at 1-
year post surger A 2-sided “t” test will be used for the analysis. 
- To demonstrate that Montage does not interfere with the repair, evaluation of the formation of new bone,
as measured by CT scans at 1-year post surgery.
- Evaluation using the VAS back pain and leg pain, Oswestry Disability Index (ODIv2.1a) and SRS-22,
which will be recorded during the study and reported as outcomes scores, and compared between the two
groups.
-Antifibrinolytics use and type will be recorded during the study and compared between the two groups
4.2  TREATMENT METHODOLOGY 
MONTAGE will be used only at a focal site where the osteotomy is performed. It will be applied to the edges 
of the spine defect after removal of the wedge. MONTAGE will be applied immediately prior to placing the 
osteotomy site under compression prior to its hardening so as to ensure no interference with compression 
against the osteotomy edges. Participating investigators, at their discretion, may use autograft and allograft 
bone void fillers for the other parts of the spine fusion as part of standard of care. 
A teaching video will be used to ensure strict adherence to the study procedure at all sites. 
Hematological parameters, such as Hb, Hematocrit, RBC, WBC, platelet counts, MCV, MCHC, and 
differential counts will be recorded and compared between the groups at baseline, immediate post-surgery, 
and daily up until day 7 or discharge (whichever comes first). 
All standard-of-care blood values, including CBC, electrolytes, liver function and kidney function tests during 
the initial hospital admission will be recorded and analyzed at certified laboratories. 
Consistent radiographic parameters will be used to evaluate the angular measurements between the 
superior endplate of the vertebral body below the PSO and the one above it. 
All radiographic images will be read by two reviewers, without knowledge of treatment groups (i.e., blinded). 
The radiographic techniques that will be employed in this study are X-rays and CT scans of the 
thoracolumbar spine without contrast, focusing on the vertebral segments above the osteotomy, the 
osteotomy segment itself, and the spinal area just below the osteotomy procedure. All images during the 
study will be read by the same two reviewers. 
4.2.1    Screening and Pre-Treatment Regimen 
4.2.1.1 Visit #1:  Screening Evaluation and Enrollment (Week -2) 
▪
Signed written Informed Consent Form will be obtained.
▪
Subjects will be enrolled according to the Inclusion and Exclusion criteria listed above.
▪
Subject demographics, medical history, and vital signs will be recorded.
▪
A blood sample will be drawn from the subject for analysis of hematological and biochemical
parameters at a central laboratory consistent with the study institutions preoperative workup
▪
Subjects will undergo pre-operative imaging using CT and radiographs, which are based on
standard of care.
▪
Patient’s co-morbidities will be scored using the Charlson Comorbidity index, the ASA score as well
as ISSG severity scores.
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▪ 
A list of pain medications with dosing will be recorded 
▪ 
VAS back and leg pain, ODIv2.1a and SRS-22 scores will be collected as a baseline. 
 
 
4.2.2 
Randomization  
 
The randomization will occur with the participating center contacting the central study data 
repository after submitting preoperative subject data; random assignment will be generated by 
computer. Patients will be randomized to either PSO with MONTAGE or standard of care 
 
 
4.2.3 
Treatment  
 
4.2.3.1 Visit #2:  Treatment Phase (Week 0) 
 
The patient will undergo the surgical intervention, excising a bone wedge from the vertebral body 
followed by a closure of the defect and re-apposition of the bony edges, creating the correction. 
Just prior to closure of the osteotomy, either MONTAGE or no bone hemostat will be placed on 
the surface of the cut bone. 
Operative parameters, including surgery time (duration of surgery) level of the osteotomy and 
type of surgery, as well as intra-operative blood loss will be recorded.  
The use of anti-fibrinolytics will be recorded.  
Regular blood values, including Hb, Hematocrit, RBC, WBC, platelet count, MCV, MCHC and 
differential counts will be performed on each post operative day while subject is in the hospital, up 
until day 7. 
Number of blood transfusions as well as any wound drain output will also be recorded.  
 
4.2.3.2 Visit #3:  Follow-up Visit (Week 2) 
 
Radiographs- standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected. 
Current Pain medications/dosing will be collected. 
Adverse Events will be recorded. 
 
4.2.3.3  Visit #4:  Follow-up Visit (Week 6) 
 
Radiographs- standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected 
Current Pain medications/dosing will be collected. 
Angular correction and gap will be measured. 
Regular blood chemistry, including Hb, Hematocrit, RBC, WBC, Platelet count, MCV, MCHC and 
differential counts will be performed (as clinically indicated). 
Adverse Events will be recorded 
 
4.2.3.4  Visit #5:  Follow-up Visit (Week 12) 
 
Radiographs- standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected 
Current Pain medications/dosing will be collected. 
Work Status will be recorded 
Angular correction and gap will be measured. 
Adverse Events will be recorded. 
 
4.2.3.5 Visit #6:  Follow-up Visit (Week 24) 
 
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Radiographs- standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected 
Current Pain medications/dosing will be collected. 
Work Status will be recorded 
Angular correction and gap will be measured. 
Adverse Events will be recorded. 
 
 
4.2.3.6  Visit #7: Follow-up visit (Week 52) 
 
Radiographs- standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected 
Current pain medications/dosing will be collected. 
Angular correction and gap will be measured. 
A CT scan will be taken to evaluate screw loosening and other measures of bone healing. 
Adverse Events will be recorded. 
 
 
4.2.3.7  Visit #8: Follow-up visit (Week 104) 
 
Radiographs standing ap and lateral scoli xrays will be completed and centrally  
read by independent evaluators. 
VAS back and leg, ODIv2.1a and SRS-22 scores will be collected 
Current Pain medications/dosing will be collected. 
Angular correction and gap will be measured. 
Adverse Events will be recorded. 
 
 
5. 
ADVERSE EVENTS (DEFINITIONS AND REPORTING) 
All adverse events reported spontaneously by the subject/or in response to questioning or observation by 
the investigator will be recorded. 
 
5.1 
ADVERSE EVENT 
 
An adverse event (AE) is defined as any unfavorable or unintended sign, symptom, or disease temporally 
associated with the use of the study products, or worsening of a pre-existing condition, whether or not it is 
considered related to the study treatment. All AEs and intercurrent illnesses must be recorded in the 
subject’s medical records and on the CRF. 
 
Adverse events will be defined as those events that occur after signing the informed consent until the final 
study visit.  A description of the AE along with the onset date, end date, severity, action taken, treatment, 
outcome, likely cause, and relationship to the study products will be recorded in the CRF.   
 
Local and systemic AEs associated with each treatment arm will be tabulated and compared. AEs will be 
elicited through direct questioning, subject reports, and physical examination. 
 
An abnormal laboratory test result is not by itself considered to be an AE unless the Investigator considers 
the finding of clinical significance that should be reported in such a manner. 
 
5.1.1 
Reporting of Adverse Events 
 
The Investigator will be responsible for assessing the relationship of the adverse event to the investigational 
product, and the seriousness and expectedness of the adverse event at the time of occurrence.  A medically 
ABYRX
Page 15 of 30

qualified person appointed by the Sponsor will also assess this, once the Sponsor has been notified of an 
AE.  All adverse events that occur during the trial will be documented on the supplied adverse event forms. 
 
AEs and serious adverse events (SAEs) reported during the study, or SAEs reported within 30 days of the 
end of the study, will be followed to resolution of the AE/SAE or, within thirty days from the end of the study, 
a further and final assessment of the outcome will be made.  
 
Each AE will be categorized as “serious” or “not serious” based on the definition of an SAE.  An SAE is 
defined as an AE resulting in at least one of the outcomes described in Section 5.2. 
 
The severity of AEs will be classified as “mild”, “moderate”, or “severe”, based on the following definitions: 
 
• 
Mild:  Awareness of sign, symptom, or event, but easily tolerated; does not interfere with usual 
daily activities or tasks. 
• 
Moderate:  Discomfort enough to cause interference with usual daily activity; may warrant 
therapeutic intervention. 
• 
Severe:  Incapacitating; inability to perform usual activities and daily tasks; significantly affects 
clinical status; requires therapeutic intervention. 
AEs will be assigned a relationship (causality) to the study products.  The Investigator will be responsible 
for determining the relationship between an AE and the study product.  The type of event, organ system 
affected, and timing of onset of the event will be factors in assessing the likelihood that an AE is related to 
the treatment.  Relationship of AEs to study products will be classified as follows: 
 
• 
Not Related:  No relationship exists between the AE and the treatment.  The event is attributed to 
a pre-existing medical condition or an intercurrent event unrelated to the study product. 
• 
Possibly Related:  Follows the treatment, but may have developed as a result of an underlying 
clinical condition or treatments/interventions unrelated to the study product. 
• 
Probably Related:  Follows the treatment, but is unlikely to have developed as a result of the 
subject’s underlying clinical condition or other treatment or other interventions. 
• 
Definitely Related:  Follows the treatment and physical evidence shows a convincing relationship 
to the treatment. 
• 
Unknown:  Follows the treatment, but unable to determine the relationship to the treatment. 
5.1.2 
Subject Follow-up 
 
Subjects who experience an AE will be followed until the AE has resolved, if possible. 
 
5.2 
SERIOUS ADVERSE EVENT 
 
A SAE will be defined as any untoward medical occurrence that occur after signing the informed consent 
until the Final Evaluation that: 
 
ABYRX
Page 16 of 30

•
Results in death,
•
Is life-threatening,
•
Requires inpatient hospitalization or prolongation of existing hospitalization,
•
Results in persistent or significant disability/incapacity,
•
Is a congenital anomaly/birth defect,
•
Other (event not covered by SAE categories but in the investigator’s opinion, should be
considered serious).
Important medical events that may not result in death, be immediately life threatening, or require 
hospitalization may be considered an SAE when, based upon medical judgment, if they may jeopardize the 
subject and require intervention to prevent one of the outcomes listed above. 
5.2.1 
Reporting Serious Adverse Events 
The Investigator must report all SAEs (including any subject deaths) occurring during the study (from 
informed consent until the Final Evaluation).  Once the Investigator becomes aware of an SAE, he/she must 
e-mail (preferred method of communication) or telephone the Sponsor within 24 hours:
Dr Jan Lessem, M.D., Ph.D 
Consultant Medical Officer 
Telephone (home):  786-916-2860 
Telephone (Sweden; May through August): 
+46-431-360167
Telephone (mobile):  857-891-6525
Email: jlessem@clinstrat.com
The Investigator is responsible for reporting all SAEs to the appropriate Institutional Review Board (IRB) in 
accordance with local laws and regulations.  The Investigator is responsible for maintaining documentation 
in the study file that indicates the IRB has been properly notified.  
5.3 
UNANTICIPATED ADVERSE DEVICE EFFECT (UADE) 
An unanticipated adverse device effect is defined as 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, or any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
5.3.1 
Reporting UADEs 
The Investigator must report all UADEs (including any subject deaths) occurring during the study (from 
informed consent until the Final Evaluation).  Once the Investigator becomes aware of an UADE, he/she 
must e-mail (preferred method of communication) or telephone the Sponsor within 24 hours: 
Dr Jan Lessem, M.D., Ph.D 
Consultant Medical Officer 
Telephone (home) : 786-916-2860 
Telephone (Sweden):  0431-360167 
Telephone (mobile):  857-891-6525 
Email: jlessem@clinstrat.com  
6.
STATISTICAL DESIGN
ABYRX
Page 17 of 30

6.1 
DESIGN 
This is a parallel group, randomized, open, multicenter, prospective study in subjects with spinal deformities 
requiring a PSO procedure at a single level.  Patients will be randomized 1:1 to receive either MONTAGE 
or no bone hemostat.  Within each randomization study group, patients will be stratified according to their 
smoking status (non-smokers versus current smokers). 
The primary objective of this study is the evaluation of post-operative blood loss in the week following 
surgery.  
The secondary outcome will be the stability of the construct, as measured by the gap between the repaired 
osteotomy edges.  In addition, observations will be made regarding whether the hardware repair has been 
maintained, and if the screws have loosened, and if the inserted rods are intact. Each repair complication 
will be categorized as belonging to one of the following groups: 1) hardware malplacement, 2) loosening or 
dislodegment, 3) nonunion or nonfusion with hardware fracture 4) nonunion or nonfusion without hardware 
fracture 5) peri-hardware fracture.  These complications will be measured with imaging, including CT scans 
performed at 1-year. Fusion failure will be determined to be present if an area of perihardware lucency 
greater than 2 mm in thickness is present. 
Malplacement of hardware will be considered present when an abnormal hardware position with hardware 
impingement on an important structure such as nerve or vessel is present.  
Other secondary objectives will include: 
- The formation of new bone at the osteotomy site, measured in mms at 1-year post surgery at the
osteotomy site.
- VAS back and leg, Oswestry Disability Index (ODIv2.1a), and SRS-22 scores which will be recorded during
the study and reported as outcomes scores, and compared between the two groups.
-Analysis of the MONTAGE/vertebral body interface, evaluating whether bony substitution has occurred at
1-year post-surgery.  The presence or absence of bony resorption around the MONTAGE will also be
reviewed.
-The use and type of antifibrinolytics will be compared between the two groups.
6.2  
SAMPLE SIZE 
A total of 50 subjects will be recruited to this study, with 1:1 randomization, stratified to ensure equal 
distribution of smokers and non-smokers within each group. 
6.3 
ANALYSIS PLAN 
The statistical analysis will be performed in conjunction with Abyrx.  Analyses will be conducted on the 
Intention-to-Treat population (ITT), with additional Per Protocol analyses.  All significance tests will be two-
sided; p-values will be provided with P(H0) < 0.05 indicating a significant difference. 
All other analyses with respect to demographic and clinical parameters will be reported with descriptive 
statistics. 
6.3.1  
Subject Analysis Sets 
The Intention-to-Treat population (ITT) is defined as all subjects receiving study treatment. 
ABYRX
Page 18 of 30

6.3.2 
Secondary Variables and Analyses 
Several secondary analyses will be carried out; the results of any secondary analyses are exploratory. 
6.3.3 
Safety 
All AEs and medications information will be listed in full. The AE information, including the responses for 
severity, seriousness, relationship to investigational product, unexpected, and outcome, will be summarized 
in a table by treatment.  
6.3.4  
Other Data Summaries 
The following variables will be summarized in tables by treatment and overall, using descriptive statistics: 
•
Reasons for discontinuing participation.
•
Treatment duration (by reason for discontinuing participation).
•
Reasons for study discontinuation
•
Study duration.
7.
ADDITIONAL INFORMATION
7.1 
USE OF ADDITIONAL MEDICAL SERVICES 
A radiological laboratory will be used as appropriate. All CT scans will be interpreted by two independent 
reviewers. 
A Certified laboratory will be used for all hematological and chemistry measurements. 
7.2 
SOURCE DATA VERIFICATION (SDV) 
To enable SDV of the trial data, direct access to the subjects’ medical records/data and source notes 
documentation will be granted to the trial monitor and to auditor(s), IRB(s)/IEC(s) and regulatory authority(-
ies), by the subject and institution/Investigator. 
The following data in the Consent form and the CRF will be checked for 100% of subjects, against the 
source notes documentation/medical records/data:  
•
Consent Form
•
Identity Number
•
Subject Initials
•
Date of Birth
•
Sex
•
Date of Subject Entry and Completion/Withdrawal from the Trial
•
CRF Assessment Dates
•
Adverse Events
•
Therapy Modifications
. 
7.3 
TRIAL MONITORING 
The Trial Monitor will telephone and visit the centers at initiation and then as frequently as is deemed 
necessary.  At a minimum, there will be one interim audit and a close-out audit. 
ABYRX
Page 19 of 30

 
7.4 
USE OF TRIAL FINDINGS 
 
The Sponsor, in conjunction with the principal investigator (PI), will prepare an analysis and a report of the 
results of the trial.  The PI shall have the right to include the material contained in this report in relevant 
articles for scientific journals or presentations at scientific meetings provided that 30 days prior to such 
publication by the Investigator the Investigator shall submit a copy of the publication or presentation paper 
to the Sponsor for verification of factual data contained in the publication or presentation paper.  The 
Sponsor shall advise the PI as soon as reasonably practical of any perceived discrepancies within the 
publication or presentation paper. The Sponsor has the right to modify the presentation/publication if in the 
opinion of the Sponsor it is likely to be in conflict with the requirements of the regulatory authorities regarding 
the regulatory status of the product in any of its international markets.  The PI and Sponsor shall conduct 
good faith discussions with the aim of resolving any discrepancies within 21 days of receipt of the proposed 
publication or presentation paper.  The PI shall provide a revised copy (if any) of the publication or 
presentation paper to the Sponsor prior to publication. 
 
 
8. 
ETHICAL AND LEGAL ISSUES 
 
8.1 
GOOD CLINICAL PRACTICES (GCP) 
 
The trial will be performed in accordance with the current ICH Good Clinical Practice Guidance for Industry, 
the Declaration of Helsinki (revised version of Somerset West, Republic of South Africa, 1996), applicable 
FDA regulations including 21 CFR 50, Protection of Human Subjects and 21CFR 56, Institutional Review 
Boards and applicable EU regulations including European Commission Directives 2001/20/EC and 
2005/28/EC. 
 
8.2 
APPROVAL OF PROTOCOL 
 
Before the start of the trial, the investigator will sign the Approval and Agreement page (Section 9) and will 
submit the trial protocol to the appropriate Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC). 
 
The first subject will not be enrolled in the trial until the Trial Monitor has received a copy of the ethics 
approvals in which the protocol is mentioned by name and number. 
 
8.3 
CONFIDENTIALITY 
 
The subject will be identified throughout the evaluation and documentation by the numbers allocated to 
them during the trial and by their initials.  The subjects will be told that all trial findings will be stored on 
computer and handled in strictest confidence.  No record of a subject’s name will be kept by the sponsor 
company. 
 
The signed informed consent forms remain with the investigators.  By signing this protocol, the investigators 
agree to obtain a correctly completed informed consent form from each subject included in the trial.  They 
also agree to keep the forms for 15 years and will allow these to be inspected on request. 
 
8.4 
INSURANCE/FINANCIAL 
 
Public/Products Liability Insurance has been purchased by Abyrx. and incorporates coverage for personal 
injury in respect of clinical trials.  The Sponsor agrees to implement in good faith the ABPI guidelines 
regarding compensation for injury arising in the course of clinical trials.  Indemnity and Financial agreements 
between the Sponsor and the trial center are appended separately. 
 
8.5 
SUBJECT CONSENT 
 
ABYRX
Page 20 of 30

Before being admitted to the clinical trial, the subject must have consented to participate, after the nature, 
scope and possible consequences of the trial have been explained in an understandable form.  The subject 
should be informed of the following aspects:  
1.
That the trial involves research, a description of the aims of the trial and how it will be
organized and the expected duration of the subject’s participation.
2.
The type of treatment and the way in which the subjects will be allocated to treatment (i.e.
by 1:1 randomization).
3.
The positive effects which can be expected of the test material.
4.
Any negative effects possibly attributable to the test material.
5.
Alternative therapeutic approaches.
6.
The freedom to ask for further information at any time.
7.
The extent, if any, to which confidentiality of records identifying the subjects will be
maintained and that the Regulatory Authorities may inspect the records.
8.
That participation is voluntary and that refusal to participate will involve no penalty or loss
of benefits to which the subject is otherwise entitled, and that the subject may discontinue
participation at any time without penalty or loss of benefits to which the subject is otherwise
entitled.
9.
The existence of adequate subject insurance coverage.
The subject’s consent must be confirmed by the signature of the Investigator or designated personnel, and 
subject.  The Sponsor will supply the investigator with an adequate number of informed consent forms.  The 
investigator will not undertake any medical measures related to the clinical trial until valid consent has been 
obtained. 
ABYRX
Page 21 of 30

9.
REFERENCES
1. Cogniet A et al: Clinical and Radiological outcome of lumbar posterior subtraction osteotomies are correlated to pelvic incidence
and FBI index: Prospective series of 63 cases. Eur.Spine J: 8; 2657-2667, 2016
2. Liu H et al: Comparison of Smith-Petersen osteotomy and pedicle subtraction osteotomy for the correction of thoracolumbar
kyphotic deformity in ankylosing spondylitis: a systematic review and meta-analysis. Spine: 40; 57-579; 2015
3. Bridwell K: Decision Making Regarding Smith- Petersen vs Pedicle Subtraction Osteotomy vs Vertebral Column Resection for
Spinal Deformity.  Spine ; 31 ( suppl) : S171-S178; 2006
4. Bridwell K et al: Pedicle subtraction osteotomy for the treatment of fixed sagittal imbalance. The Journal of Bone and Joint
Surgery 85: 454-463; 2003
5. Seung-Jae H et al: Spinal Pedicle subtraction osteotomy for fixed sagittal imbalance patients. World J. Clin. Case 1: 242-248;
2013
6. Lee El et al: Outcomes of calvarial reconstruction in cancer patients. Plast. Reconstr. Surg. 133; 675-682; 2014
7. Cheng, L., et al., Osteoinduction of hydroxyapatite/beta-tricalcium phosphate bioceramics in mice with a fractured fibula. Acta
Biomater, 2010. 6(4): p. 1569-74.
8.Pripatnanont, P., et al., Bone Regeneration Potential of Biphasic Nanocalcium Phosphate with High Hydroxyapatite/Tricalcium
Phosphate Ratios in Rabbit Calvarial Defects. Int J Oral Maxillofac Implants, 2016. 31(2): p. 294-303.
9. Koshiyama, H. and K. Yamazaki, Absorbable sternal pins improve sternal closure stability within a small deviation. Gen Thorac
Cardiovasc Surg, 2015. 63(6): p. 331-4
10  Baumgart, D., et al., Primary closure of median sternotomy with interposition of hydroxyapatite blocks. A new approach in
pediatric cardiac surgery. Eur J Cardiothorac Surg, 1991. 5(7): p. 383-5.
11.Barbanti Brodano, G., et al., A post-market surveillance analysis of the safety of hydroxyapatite-derived products as bone graft
extenders or substitutes for spine fusion. Eur Rev Med Pharmacol Sci, 2015. 19(19): p. 3548-55
12.Yi, S., et al., Biomechanical Comparisons of Pull Out Strengths After Pedicle Screw Augmentation with Hydroxyapatite, Calcium
Phosphate, or Polymethylmethacrylate in the Cadaveric Spine. World Neurosurg, 2015. 83(6): p. 976-81.
ABYRX
Page 22 of 30

APPENDIX I 
Montage Time/Events Table 
Interval 
Baseline/   
Screening 
Operative/
Discharge 
Week 
2 
Week 
6 
Week 
12 
Week 
24 
Week 
52 
Week 
104 
Range 
Within 30 
days of 
Surgery 
N/A 
+/- 4 
days 
+/- 2 
wks 
+/- 2 
wks 
+/-3 
wks 
+/- 6 
wks 
+/- 6 wks 
Consent 
X 
Randomization 
X 
Treatment 
X 
Physical (neuro) 
Exam 
X 
X 
X 
X 
X 
X 
X 
Medical History 
X 
Charlson Comorbidity 
index, ASA and ISSg 
X 
VAS 
X 
X 
x 
X 
X 
X 
X 
ODI 
X 
X 
X 
X 
X 
X 
X 
SRS-22 
? 
X 
X 
X 
X 
X 
X 
Work Status 
X 
X 
X 
X 
X 
X 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Smoking Status 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry (Hb, 
Hct, RBC, WBC, 
Platelet count, MCV, 
MCHC and 
differentials 
X 
X1 
X1 
X1 
X1 
X1 
X1 
X1 
SAE/AE 
X 
X 
X 
X 
X 
X 
X 
Operative data 
collection 
X 
IMAGING 
Radiographs 
X 
X 
X 
X 
X 
X 
X 
CT Scan 
X 
X 
Angular Correction 
and gap 
measurement 
X 
X 
X 
X 
1to be 
completed 
if standard 
of care 
v.3.22.18
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 23 of 30

 
APPENDICES A-C HAVE BEEN ADDED TO THE DOCUMENT FOR ABYRX USE ONLY 
AND DO NOT HAVE ANY IMPACT ON THE PROTOCOL. 
Appendix A: Essential Clinical Investigation Documents Prior to Clinical Investigation 
Doc # 
Title 
Purpose/Comments 
Reference 
to Standard 
Included 
(with date) 
A1 
Investigators Brochure (IB) 
Describes the investigational 
device, including instructions for 
device use. 
5.5, Annex B 
A2 
Clinical Investigation Plan (CIP) 
Describes the clinical 
investigation design and 
procedures. 
5.4, Annex A 
A3 
Sample of labelling attached to the 
investigational device 
Confirms appropriate labelling. 
5.10 
A4 
Principal Investigators current CV, 
signed and dated 
Identifies the principal 
investigator. The site has CVs for 
principal investigators at that 
site; the sponsor has CVs for 
principal investigators from all 
investigation sites. 
4.5.2(e), 
9.2(a), 
Annex 
D.13(c)
A5 
Current CV of key members of the 
investigation site team, signed 
and dated 
Identifies the key members of 
the investigation site team. The 
site has CVs for key members of 
investigation site team at that 
site. 
9.2 (a) 
A6 
CV or other qualification 
documentation of individuals 
other than those cited in A4 and 
A5, who materially contribute to 
the clinical investigation, signed 
and dated 
Documents qualification of all 
other parties involved in clinical 
investigation. 
5.1, 8.2.1, 
8.2.4.3 
A7 
Log of principal investigator and 
key members of investigation site 
team at each investigation site 
Documents the attribution of 
responsibilities, with signature, 
title, and responsibilities in the 
clinical investigation. 
6.2, 8.2.1(e), 
8.2.4.5 (b) 
A8 
List of investigation sites 
Evidences who is conducting the 
clinical investigation, with 
names and addresses. 
Annex A 1.4 
A9 
Ethics committee (EC) 
notification, correspondence and 
opinion/approval 
Gives evidence that a qualified, 
independent EC has reviewed 
the clinical investigation. 
4.5.3, 6.1, 
8.2.2(g), 9.4 
A10 
EC voting list for the clinical 
investigation 
Provides evidence that the 
investigator is not part of the 
voters (dependent on regulatory 
requirements). 
4.5.3 
A11 
Regulatory authority notification, 
correspondence and approval 
(where required)  
Verifies information provided to 
regulatory authorities. Confirms 
notification or approval. 
6.1, 8.2.2(f) 
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 24 of 30

 
Doc # 
Title 
Purpose/Comments 
Reference 
to Standard 
Included 
(with date) 
A12 
Signed agreement between 
principal 
investigator(s)/investigation 
site(s) and sponsor  
Demonstrates understanding of 
each party's respective 
responsibilities. 
5.9, 8.2.1(a), 
8.2.2(e) 
A13 
Signed agreements between 
sponsors and third parties, e.g. 
CRO, core laboratories 
Demonstrates understanding of 
each party's responsibilities. 
5.9, 8.2.1(a) 
A14 
Financial agreements, if separate 
from agreements on 
responsibilities 
Provides evidence of financial 
arrangements between 
investigator/ investigation site 
and sponsor (can be kept 
separate from other site files). 
8.2.2(e) 
A15 
Insurance certificates, if 
applicable 
Gives evidence that 
compensation to subject(s) for 
clinical investigation-related 
injuries will be available. 
4.3, 4.5.2(j), 
8.2.2(d) 
A16 
Shipping records for 
investigational devices 
Verifies physical possession of 
devices. 
6.9, 8.2.2(c), 
8.2.3(a), 
8.2.4.5(l), 
9.6(k) 
A17 
Shipping records for clinical 
investigation-related documents 
and materials 
Verifies physical shipment of 
documents and materials. 
8.2.2(c) 
A18 
Sample of approved informed 
consent forms, information for the 
subjects and advertisements, 
including translations 
Gives evidence of the content of 
the informed consent forms and 
of the information provided to 
the subject during the clinical 
investigation. 
4.5, 4.7, 
8.2.2(a) 
A19 
Randomization list for 
randomized clinical investigations 
Verifies that randomization has 
been followed. Depending on the 
design of the clinical 
investigation, the list might not 
be available at the investigation 
site for blinded/masked clinical 
investigations. 
6.8.1 
A20 
Decoding procedures for 
blinded/masked clinical 
investigations, where applicable 
Might not take place on the 
investigation site depending on 
study design.  
6.8.1, Annex 
A6.1(a), 
A16(b) 
A21 
Investigation site selection report 
Verifies that qualifications of 
investigator and investigation 
site have been reviewed. 
5.8, 8.2.1(b), 
8.2.4.3, 
8.2.4.7 
A22 
Clinical investigation initiation 
monitoring report 
Verifies that investigator and 
investigation site team have 
been trained to device use and 
CIP compliance 
6.2, 8.2.4.7 
A23 
Follow-up letter further to clinical 
investigation initiation 
monitoring; correspondence with 
the investigation site 
Identifies any findings and 
actions to the investigation site. 
8.2.4.7 
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 25 of 30

 
Doc # 
Title 
Purpose/Comments 
Reference 
to Standard 
Included 
(with date) 
A24 
Case Report Forms (CRF) 
Blank set to evidence toe content 
of data being collected 
5.6, Annex C 
A25 
Adverse Event Forms 
Documents all adverse events as 
required by the standard (Forms 
may or may not be part of CRF) 
5.6, 6.4.1, 
Annex C 
A26 
Device Deficiency Forms 
Document all device deficiencies 
(Forms may or may not be part 
of CRF) 
5.6, 6.4.2, 
Annex C 
A27 
Name/Contact information of 
Monitor(s) 
Document the person who has 
ensured continuing compliance 
of the clinical investigation. 
5.1, 8.2.1 (a) 
8.2.1 (f) 
Annex 
D.13(e)
A28 
Training Records 
Provides evidence that 
investigator(s) have been 
trained in the use of the 
investigational device and all 
relevant aspects of the clinical 
investigation. 
8.2.1(g) 
A29 
Disclosure of conflicts of interest 
Documentation of conflicts of 
interest, e.g. financial. 
8.2.1(d), 
9.2(c) 
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 26 of 30

 
 
Appendix B: Essential Clinical Investigation Documents During Clinical Investigation 
 
Doc # 
Title 
Purpose/Comments 
Reference to 
Standard 
Included 
(with date) 
B1 
Investigators Brochure (IB) 
amendments, if any 
Documents changes to the IB 
6.5.1 
 
B2 
Clinical Investigation Plan 
(CIP) amendments, if any 
Documents changes to the CIP 6.5.1 
 
B3 
Sample of amendments to 
informed consent form 
 
6.5.1 
 
B4 
Ethics Committee (EC) 
opinion/approval of any 
amendments 
 
4.5.4(d), 
4.5.5(a), 
8.2.3(b), 
8.2.4.5(m), 
9.4( c) 
 
B5 
Notices or approvals to 
regulatory authorities of any 
amendments, where required 
Verifies information provided 
to authorities, confirms 
notification of approval 
6.1, 8.2.2(f), 
8.2.2(h) 
 
B6 
New Principal Investigators 
current CV, signed and dated 
Identifies the principal 
investigator. The site has CVs 
for principal investigators at 
that site; the sponsor has CVs 
for principal investigators 
from all investigation sites. 
4.5.2(e), 
9.2(a),  
Annex 
D.13(c) 
  
B7 
CV of new key members of the 
investigation site team, signed 
and dated 
Identifies the key members of 
the investigation site team. 
The site has CVs for key 
members of investigation site 
team at that site. 
9.2 (a) 
 
B8 
Shipping records and 
investigational device 
accountability records 
 
6.9, 8.2.2(c), 
8.2.3(a), 
8.2.4.5(l), 
9.6(k) 
 
B9 
Shipping records for clinical 
investigation-related 
documents and materials 
 
8.2.4.4(a) 
 
B10 
Monitoring visit reports 
Provides summary of key 
findings to the principal 
investigator 
8.2.3(d), 
8.2.4.7 
 
B11 
Correspondence related to the 
clinical investigation, including 
emails, letters, meeting notes, 
and phone reports 
 
8.2.3(b), 
8.2.4.5(m), 
9.6(o) 
 
ABYRX
Page 27 of 30

 
 
Doc # 
Title 
Purpose/Comments 
Reference to 
Standard 
Included 
(with date) 
B12 
Updated log of principal 
investigator and key members 
of investigation site team at 
each investigation site, 
including signature, title, and 
responsibility in the clinical 
investigation 
Documents the attribution of 
responsibilities 
6.2, 8.2.1(e), 
8.2.4.5 (b) 
 
B13 
Signed, dated, and fully 
executed informed consent 
forms 
Verifies that informed consent 
has been given 
4.7.1, 7.4, 
8.2.4.5(f), 
9.5 
 
B14 
Source documents 
 
6.5.3, 6.8.2, 
9.6(o), 
9.7(f) 
 
B15 
CRFs, fully executed 
Evidences what data were 
collected and that their 
authenticity has been verified 
by the PI 
6.3, 6.8.1, 
6.8.2, 
8.2.4.5(i), 
9.6(j) 
 
B16 
Reports of adverse events, 
adverse device effects, and 
device deficiencies 
Documents the occurrence 
and resolution of adverse 
events and adverse device 
effects 
6.4, 
8.2.4.5(j)(k), 
8.2.5, 9.8, 
Annex D 
13(g) 
 
B17 
CRF corrections 
Gives evidence of any 
changes, additions, or 
corrections made to CRFs 
after data were initially 
recorded 
6.8, 
8.2.4.5(i), 
9.6(j) 
 
B18 
Reports of adverse events or 
device deficiencies by sponsor 
to regulatory authorities or by 
the PI, where applicable 
Filing in investigation sites 
only where national 
regulations require 
notification by the PI 
6.4, 7.1, 
8.2.5, 9.8 
 
B19 
Reports of adverse events by 
the PI or the sponsor to the EC, 
where required 
 
4.5.4 
 
B20 
Reports by sponsor to 
investigators of adverse events 
occurring at other investigation 
sites 
 
8.2.5 
 
B21 
Interim or annual reports by PI 
to EC, where applicable 
 
4.5.4, 
8.2.3(b), 
8.2.4.5(m), 
9.4, 9.8 
 
B22 
Subject screening log 
 
6.5.2 
 
B23 
Subject identification log 
 
6.5.2 
 
ABYRX
Page 28 of 30

 
Doc # 
Title 
Purpose/Comments 
Reference to 
Standard 
Included 
(with date) 
B24 
Accountability logs of all the 
investigational devices at the 
investigational site, where 
appropriate 
6.9, 8.2.3(a), 
8.2.4.5(l), 
9.6(k) 
B25 
Updated Name/Contact 
information of Monitor(s), 
where applicable 
Document the person who has 
ensured continuing 
compliance of the clinical 
investigation. 
8.2.1 (a) 
8.2.1 (f) 
Annex 
D.13(e)
B26 
Disclosure of conflicts of 
interest   
Documentation of conflicts of 
interest, e.g. financial. 
8.2.1(d), 
9.2(c) 
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 29 of 30

 
Appendix C: Essential Clinical Investigation Documents After Clinical Investigation 
Doc # 
Title 
Purpose/Comments 
Reference to 
Standard 
Included 
(with date) 
C1 
Investigational device 
accountability at each 
investigation site 
6.9, 7.2(a), 
9.6(k)(o) 
C2 
Documentation of investigational 
device return/disposal, where 
applicable 
Documents the proper disposal 
of biohazardous materials or 
other materials that require 
special disposal 
6.9, 7.2(a), 
9.6(k) 
C3 
Completed subject identification 
log 
6.5.2 
C4 
Audit certificate (If required or 
conducted) 
6.11, 8.1, 
Annex 
D.13(h)
C5 
Close out monitoring report 
8.2.4.7 
C6 
Notification of clinical 
investigation close out to the 
Ethics Committee by principal 
investigator(s) or sponsor, where 
required 
4.5.4, 7.1, 
7.2, 8.2.6(d), 
9.4 
C7 
Notification of the clinical 
investigation close out to the 
regulatory authorities by the 
principal investigator(s) or 
sponsor, where required 
7.1, 7.2, 
8.2.6(d) 
C8 
Sponsor’s statistical analyses and 
clinical investigation report 
7.3, 8.2.6, 
Annex D 
ABYRX
D-000741A: CIP -
A Prospective, Multicenter, Randomized, Controlled Clinical Investigation of MONTAGE 
in Adults with Spinal Deformity Undergoing Pedicle Subtraction Osteotomy
ECO 2009
NOTE: THIS IS A COPY OF THE PROTOCOL, WHICH IS ON FILE WITH WIRB. 
ABYRX HAS ISSUED A D-DOCUMENT NUMBER TO THE PROTOCOL FOR TRACEABILITY PURPOSES IN ACCORDANCE WITH THE ABYRX QMS. 
NO CHANGES MAY BE MADE TO THIS DOCUMENT WITHOUT APPROVAL AND ISSUANCE FROM WIRB.  
Page 30 of 30