A Prospective, Single Blinded, Multi-center, Randomized, Controlled, Pivotal Study to Assess the Safety and Effectiveness of the InSpace™ Device for Treatment of Full Thickness Massive Rotator Cuff Tears
Phase: NA
Conditions: Rotator Cuff Syndrome
Sponsor: OrthoSpace Ltd.

 
 
 
InSpace™ Clinical Investigational Plan 
 
Study Title: 
A 
prospective, 
single 
blinded, 
multi-center, 
randomized, 
controlled, pivotal study to assess the safety and effectiveness of 
the InSpace™ device for treatment of full thickness Massive 
Rotator Cuff Tears 
 
Version No: 
Version 4.0   
Version Date: 
March 26, 2018 
 
Study Device: 
            InSpace™ Device 
CIP NCT No.: 
 
NCT02493660CLD-OR-010 
Sponsor:                                 Ortho-Space Ltd. 
7 Halamish St. Caesarea,  
308890, Israel 
 
 
 
 
 
 
Sponsor’s Contact Person:  Heather Neill, VP Clinical Operations 
 
 
Confidentiality Statement: 
The information contained in this Clinical Investigational Plan is provided to you in 
confidence, for review by you, your staff and an applicable regulatory authority or 
institutional review committee. It is understood that this information may not be 
disclosed to any other party, in any form, without prior authorization from Ortho-
Space Ltd., except to the extent necessary to obtain informed consent from the persons 
on whom the medical device may be used. 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 1 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
TABLE OF CONTENTS 
STUDY PROTOCOL SIGNATURE PAGE ............................................................................4 
STUDY SYNOPSIS ....................................................................................................................5 
TABLE 1:  STUDY FLOWCHART AND FOLLOW-UP ASSESSMENTS ........................7 
1 
BACKGROUND INFORMATION ....................................................................................9 
1.1 
Introduction ............................................................................................................................................... 9 
1.2 
Device Name and Intended Use ............................................................................................................... 10 
1.3 
Investigational Device ............................................................................................................................. 11 
1.4 
Regulatory Status and Human Clinical Data ........................................................................................... 13 
1.5 
Mode of Action ........................................................................................................................................ 15 
2 
OVERVIEW OF INVESTIGATIONAL PLAN .............................................................16 
2.1 
Objectives ................................................................................................................................................ 16 
2.1.1 
Primary Objectives .......................................................................................................................... 16 
2.1.2 
Secondary Objectives ....................................................................................................................... 16 
2.2 
Endpoints ................................................................................................................................................. 16 
2.2.1 
Primary Composite Endpoint .......................................................................................................... 16 
2.2.2 
Secondary Endpoints ....................................................................................................................... 16 
2.2.3 
Safety Assessment ............................................................................................................................ 17 
3 
PROTOCOL .......................................................................................................................17 
3.1 
Study Design ............................................................................................................................................ 17 
3.2 
Subject Recruitment and Screening ......................................................................................................... 18 
3.3 
Study Blinding ......................................................................................................................................... 19 
3.4 
Study Duration and Follow-up ................................................................................................................ 19 
3.5 
Randomization ......................................................................................................................................... 19 
3.6 
Selection of Subjects ................................................................................................................................ 19 
3.6.1 
Inclusion Criteria ............................................................................................................................. 19 
3.6.2 
Exclusion Criteria ............................................................................................................................ 21 
3.7 
Early Withdrawal of Subjects .................................................................................................................. 23 
3.7.1 
When and How to Withdraw Subjects .............................................................................................. 23 
3.7.2 
Data Collection and Follow-up for Withdrawn Subjects ................................................................. 23 
3.7.3 
Study Site Termination ..................................................................................................................... 23 
3.8 
Prior and Concomitant Therapy ............................................................................................................... 24 
3.9 
Study Interventions – Full Thickness MRCT .......................................................................................... 24 
3.9.1 
Clinical and Functional Assessments .............................................................................................. 24 
3.9.2 
Magnetic Resonance Imaging (MRI) ............................................................................................... 25 
3.9.3 
Ultrasound ....................................................................................................................................... 26 
3.10 
Visit Summary ......................................................................................................................................... 26 
3.10.1 
Visit 1:  Screening/Baseline (days - 45 to - 1) ................................................................................. 26 
3.10.2 
Visit 2: Surgery: (day 0) .................................................................................................................. 27 
3.10.3 
Visit 3:  Day 10 Follow-Up (+/- 6 days) .......................................................................................... 29 
3.10.4 
Visit 4:  Week 6 Follow-Up (+/- 7 days) .......................................................................................... 29 
3.10.5 
Visit 5: Month 3 Follow-Up (+/- 14 days) ....................................................................................... 30 
3.10.6 
Visit 6: Month Follow-Up (+/-14 days) ........................................................................................... 30 
3.10.7 
Visit 7: 12 Month Follow-Up (+/-1 month) ..................................................................................... 31 
3.10.8 
Visit 8: Month 24 Follow-Up (+/-2 months) .................................................................................... 31 
3.10.9 
Optional Follow-Up Visit, Unscheduled Visit Procedures .............................................................. 32 
3.10.10 
Post-operative Rehabilitation Guideline ..................................................................................... 32 
3.11 
Receiving, Storage, Dispensing and Return of Investigational Product .................................................. 32 
3.11.1 
Receipt and accountability ............................................................................................................... 32 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 2 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.11.2 
Storage ............................................................................................................................................. 33 
3.11.3 
Dispensing of Investigational Device .............................................................................................. 33 
3.11.4 
Return or Destruction of Investigational Product ........................................................................... 33 
4 
STATISTICAL ANALYSIS ..............................................................................................33 
4.1 
Treatment Groups .................................................................................................................................... 33 
4.2 
Description of Study Endpoints ............................................................................................................... 34 
4.2.1 
Primary Composite Endpoint .......................................................................................................... 34 
4.2.2 
Secondary Endpoints ....................................................................................................................... 35 
4.2.3 
Safety Assessments ........................................................................................................................... 36 
4.2.4 
Radiographic Assessments ............................................................................................................... 36 
4.3 
Hypotheses ............................................................................................................................................... 37 
4.4 
Sample Size Determination and Rationale............................................................................................... 37 
4.5 
Randomization ......................................................................................................................................... 39 
4.6 
Stratification and Site Blocking ............................................................................................................... 39 
4.7 
Blinding ................................................................................................................................................... 39 
4.7.1 
Study Blinding .................................................................................................................................. 39 
4.7.2 
Subject Blinding ............................................................................................................................... 39 
4.8 
Interim Analysis (IA) ............................................................................................................................... 40 
4.8.1 
Procedures for Interim Analysis ...................................................................................................... 40 
4.8.2 
Conditional Power Calculation ....................................................................................................... 41 
4.8.3 
Rules and Method for Increasing Sample Size ................................................................................. 42 
4.9 
Effectiveness Analyses ............................................................................................................................ 43 
4.10 
General Statistical Considerations ........................................................................................................... 43 
4.11 
Analysis Populations ............................................................................................................................... 43 
4.11.1 
Intent-to-Treat Population ............................................................................................................... 43 
4.11.2 
Per Protocol Population .................................................................................................................. 43 
4.11.3 
Safety Population ............................................................................................................................. 44 
4.11.4 
Covariates ........................................................................................................................................ 44 
4.11.5 
Missing Data .................................................................................................................................... 44 
4.11.6 
Multiple Comparisons and Multiplicity ........................................................................................... 44 
4.12 
Statistical Methods ................................................................................................................................... 45 
4.12.1 
Subject Disposition .......................................................................................................................... 46 
4.12.2 
Demographic and Baseline Characteristics .................................................................................... 46 
4.12.3 
Protocol Deviations ......................................................................................................................... 46 
4.12.4 
Prior and Concomitant Medications ............................................................................................... 46 
4.12.5 
Primary Endpoint Analysis .............................................................................................................. 46 
4.12.6 
Secondary Endpoint Analyses .......................................................................................................... 47 
4.12.7 
Other Outcome Analyses ................................................................................................................. 47 
4.12.8 
MRI .................................................................................................................................................. 47 
4.12.9 
Safety Analyses ................................................................................................................................ 48 
5 
SAFETY AND ADVERSE EVENTS ...............................................................................49 
5.1 
Definitions ............................................................................................................................................... 49 
5.1.1 
Adverse Event .................................................................................................................................. 49 
5.1.1.1 
Expected Adverse Events ................................................................................................................. 49 
5.1.2 
Adverse Device Effect ...................................................................................................................... 49 
5.1.3 
Serious Adverse Events .................................................................................................................... 49 
5.1.4 
Unanticipated Adverse Device Effect (United States)...................................................................... 50 
5.1.5 
Reportable Incident (Canada) ......................................................................................................... 50 
5.2 
Recording of Adverse Events and Incidents ............................................................................................ 50 
5.3 
Reporting ................................................................................................................................................. 51 
5.3.1 
Adverse Event Reporting Period ...................................................................................................... 51 
5.3.2 
Reporting Adverse Events ................................................................................................................ 51 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 3 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
5.3.3 
Reporting Serious Adverse Events and Incidents ............................................................................. 53 
5.3.4 
Informed Consent Violation Reporting ............................................................................................ 56 
5.3.5 
Protocol Deviation Reporting .......................................................................................................... 56 
5.3.6 
Progress Reports ............................................................................................................................. 56 
5.3.7 
Final Report ..................................................................................................................................... 57 
5.4 
Unblinding Procedures ............................................................................................................................ 57 
5.5 
Data Safety Monitoring Board ................................................................................................................. 57 
5.6 
Study Stopping......................................................................................................................................... 57 
5.7 
Medical Monitoring ................................................................................................................................. 58 
5.8 
Assessment of Risks and Benefits ........................................................................................................... 58 
5.8.1 
Risks of Procedure ........................................................................................................................... 58 
5.8.2 
Risks of Study Device ....................................................................................................................... 59 
5.8.3 
Benefits of Study Device .................................................................................................................. 59 
6 
DATA HANDLING AND RECORD KEEPING ............................................................60 
6.1 
Confidentiality ......................................................................................................................................... 60 
6.2 
Source Documents ................................................................................................................................... 61 
6.3 
Case Report Forms .................................................................................................................................. 61 
6.4 
Data Management .................................................................................................................................... 62 
6.5 
Records Retention .................................................................................................................................... 62 
7 
STUDY MONITORING, AUDITING, AND INSPECTING .........................................62 
7.1 
Study Monitoring ..................................................................................................................................... 62 
7.2 
Auditing and Inspecting ........................................................................................................................... 63 
8 
ETHICAL CONSIDERATIONS ......................................................................................63 
8.1 
Protocol Amendments ............................................................................................................................. 64 
8.2 
Informed Consent .................................................................................................................................... 64 
9 
INVESTIGATOR TRAINING .........................................................................................65 
9.1 
Investigator Training ............................................................................................................................... 65 
9.2 
Training of Study Staff ............................................................................................................................ 65 
10 PUBLICATION PLAN ......................................................................................................66 
11 INSTITUTIONAL REVIEW BOARD / RESEARCH ETHICS BOARD ....................66 
12 REFERENCES ...................................................................................................................68 
13.0   APPENDICES ................................................. ERROR! BOOKMARK NOT DEFINED. 
13.1 
Appendix A: Sample Core Informed Consent Form................................. Error! Bookmark not defined. 
13.2 
Appendix B: Recommended Surgical Technique/Instruction for Use ...... Error! Bookmark not defined. 
13.3 
Appendix C: Draft Shoulder Imaging (MRI) Assessment Guidance ........ Error! Bookmark not defined. 
13.4 
Appendix D: Sample Financial Disclosure ............................................... Error! Bookmark not defined. 
13.5 
Appendix E: Draft Monitor Plan .............................................................. Error! Bookmark not defined. 
13.6 
Appendix F: Draft Rehabilitation Guidelines ........................................... Error! Bookmark not defined. 
13.7 
Appendix G: Draft Case Report Forms .................................................... Error! Bookmark not defined. 
13.8 
Appendix H: Week 6 Draft Shoulder Imaging (MRI) Acquisition Guidance......... Error! Bookmark not 
defined. 
 
 
 
 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 4 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
 
STUDY PROTOCOL SIGNATURE PAGE 
 
Confidentiality Statement:    
This Clinical Investigational Plan (CIP) contains privileged or confidential information, which is 
the property of the Sponsor. Information may not be disclosed to a third party without written 
authorization from the Sponsor. 
 
Regulatory Statement: 
This study will be conducted according to the protocol, the US Code of Federal Regulations 21 
CFR Part 50, 54, 56, and 812, the ethical principles originating from the Declaration of Helsinki, 
and Good Clinical Practice (GCP) as defined in ICH E6, and the ICH Guidelines. All aspects of 
this study will be conducted in accordance with all national, state, and local laws of the pertinent 
regulatory authorities.  
 
Investigator’s Statement: 
I understand the protocol “A prospective, single blinded, multi-center, randomized, controlled, 
pivotal study to assess the safety and effectiveness of the InSpace™ device for treatment of full 
thickness Massive Rotator Cuff Tears.” 
I agree to conduct this study in accordance with the design and specific provisions of the 
protocol in this CIP, the Clinical Study Research Agreement, and all applicable regulations, and 
to inform all who assist me in the conduct of this study of their responsibilities and obligations.  
I agree to ensure the rights, safety, and well-being of the subjects involved in the study. 
I agree to await Institutional Review Board (IRB)/Research Ethics Board (REB) approval of the 
CIP and Informed Consent Form (ICF) before initiating the study, to obtain informed consent 
prior to subject enrollment in the study, to collect and record data as required by this CIP and 
corresponding Case Report Forms (CRF), to prepare Annual, Final, and Adverse Events (AE) 
Reports as required, and to maintain study documentation for the period of time required. 
 
 I agree to maintain responsibility for all medical devices under investigation. 
 
Investigator’s Printed Name:  
                                       
 
 
Investigator’s Signature: 
 
Date of Signature: 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 5 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
STUDY SYNOPSIS 
 
Title 
A prospective, single blinded, multi-center, randomized, controlled, 
pivotal study to assess the safety and effectiveness of the InSpace™ 
device for treatment of full thickness Massive Rotator Cuff Tears 
Short Title 
InSpace device  
Protocol Number CLD-OR-010 
Study Design 
Prospective, single blinded, multi-center, randomized, controlled,  
pivotal  
Study Duration 
48 months total (approximately 24 month enrollment + 24 month 
follow-up) 
Study Center(s) 
Up to 20 clinical sites (US and Canada) 
Number of 
Subjects 
184 subjects  
Objectives 
Primary: 
• To evaluate the safety and effectiveness of the InSpace device as a 
primary surgical treatment for full thickness massive rotator cuff 
tears  
Secondary: 
• Change in clinical outcomes compared to baseline 
Study Population Male and female ≥ 40 years of age presenting with a full thickness 
massive rotator cuff tear (MRCT) 
Study Treatment  Group I: InSpace device 
Control 
Treatment  
Group II: Partial Repair  
Randomization 
Scheme 
Subjects will be assigned by a 1:1 schema 
Route of 
Administration 
Arthroscopic surgical implantation of the InSpace device 
Endpoints: 
Primary Composite Endpoint 
• WORC improvement of 275 points by Week 6 from pre-operative 
baseline and maintained at Month 12 
• ASES improvement of 6.4 points by Week 6 from pre-operative 
baseline and maintained at Month 12 
• No subsequent secondary surgical interventions (SSSI) in the index 
shoulder through Month 12 
• Absence of Serious Adverse Device Effects (SADEs), through 
Month 12 
 Secondary Endpoints: 
Clinical endpoints 
• Composite endpoint component-level success for WORC 
compared to baseline 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 6 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Composite endpoint component-level success for ASES compared 
to baseline 
• Change in Western Ontario Rotator Cuff Index (WORC) 
questionnaire scores from baseline  
• Change in American Shoulder and Elbow Surgeons (ASES) from 
baseline 
• Change in Constant Murley Shoulder Outcome Score from baseline 
• Change in EuroQOL five dimensions questionnaire (EQ-5D-5L) 
from baseline 
• Change in Visual Analogue Scale (VAS) scores from baseline 
• Change in Range of Motion (ROM) from baseline 
• Composite endpoint success at Month 24 
Imaging endpoints will include reading of MRI scans conducted at 
• 
Week 6 post treatment to assess (Group I: InSpace device 
[includes only subjects enrolled under Protocol V3.0, May 
1, 2017]): 
i. device location in the sub-acromial space 
• 
Month 12 post treatment to assess (all randomized 
subjects): 
i. the device residuals (Group I – InSpace only)  
the shoulder joint and surrounding tissue condition     (Group I: 
InSpace device and Group II: Partial Repair)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 7 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
TABLE 1:  STUDY FLOWCHART AND FOLLOW-UP ASSESSMENTS 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Days  
- 45 to -1 
Day 0 
Day 10 
±       
6 d 
Wk 6 
±       
7 d 
M 3 
±        
14 d 
M 6 
±        
14 d 
M 12  
± 
1 m 
M 24 
±       
2 m 
Informed Consent 
X1 
 
 
 
 
 
 
 
Pregnancy Test  (if 
applicable) 
 
X2 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Subject Eligibility 
Criteria Verification  
X 
X 
 
 
 
 
 
 
Subject 
Randomization 
 
X3 
 
 
 
 
 
 
Subject Treatment 
 
X5 
 
 
 
 
 
 
Magnetic Resonance 
Imaging  (MRI)  
X4 
 
 
X6 
 
 
 
X7 
 
Western Ontario 
Rotator Cuff  Index 
(WORC)  
X 
 
X 
X 
X 
X 
X 
X 
American Shoulder 
and Elbow Surgeons 
(ASES) 
X 
 
X 
X 
X 
X 
X 
X 
EuroQOL five 
dimensions 
questionnaire (EQ-5D-
5L) 
X 
 
X 
X 
X 
X 
X 
X 
Constant-Murley 
Shoulder Outcome 
Score 
X 
 
 
X 
X 
X 
X 
X 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 8 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Visual Analogue Scale 
(VAS) 
X 
 
X 
X 
X 
X 
X 
X 
Adverse Events  
 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medications Review 
X 
X 
X 
X 
X 
X 
X 
X 
 
1. Must occur prior to any study-specific procedures. 
2. If applicable, a pregnancy test, urine or blood, will be performed no earlier than 2 days 
before the scheduled surgery. 
3. Interactive web randomization performed after intra-operative inclusion confirmed. 
4. Pre-operative MRI taken within 9 months of enrollment.  
5. Subject will be blinded to treatment assignment until end of study. 
6. MRI to all study treatment arm subjects  (Group I: InSpace device [includes only subjects 
enrolled under Protocol V3.0, May 1, 2017])at Week 6 per Imaging Acquisition guidance 
(provided in Appendix H)  
7. MRI to all randomized subjects as per imaging Acquisition guidance (provided in 
Appendix C). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 9 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
1 
 BACKGROUND INFORMATION  
 
1.1 
Introduction 
 
Rotator cuff tears (RCTs) are amongst the most common orthopaedic condition in adults.  The 
incidence of rotator cuff tears increases in frequency with age (Lehman, 1995) and is often 
associated with degeneration of the tendons (Matava, 2005).  Full thickness tears of the rotator 
cuff are among the most common sources of pain and dysfunction in the shoulder (Bunker, 
2002).  Approximately 18 million Americans self-reported shoulder pain in 2005.  By 2030, over 
20% of the US population will be over 65, with that the prevalence of rotator cuff disorders are 
expected to increase over the next two decades (AAOS, 2013).   
RCTs are classified by the size of the tear (Matthews, 2006), the presence of tendon retraction, 
chronicity of the injury (Coleman, 2003; Liu, 2011) and the amount of muscle atrophy and 
degree of fatty degeneration (Harryman, 1991; Goutallier, 2007; Encalada-Diaz, 2011).  Tears 
may range in severity from partial to massive.  
Massive tears, commonly defined as a tear is greater than 5 centimeters in diameter (Cofield, 
1985) are frequently associated with pain, weakness, and functional disability (Jost, 2006; 
Gartsman, 1997).  Furthermore, these massive tears have demonstrated unfavorable outcomes 
following conservative care, necessitating surgical intervention. 
Although technically challenging, complete primary repair of the massive tear may be achieved 
through open or arthroscopic procedures (Mellado, 2005). When a patient has pain and weakness 
in the setting of a massive tear which may not be amenable to complete repair, there are a variety 
of potential treatment options (Elhassan, 2008).  These options may include conservative 
management (e.g., physical therapy) (Walch, 2005), simple decompression and debridement with 
or without biceps tenotomy (or tenodesis), subscapular nerve release, biologic augmentation, 
tendon transfer, partial repair, and reconstruction with hemiarthroplasty or reverse shoulder 
arthroplasty (Encalada-Diaz, 2011; Moser, 2007; Aurora, 2007; Goldberg, 2008; Cuff, 2008; 
Berth, 2010). A thorough history and physical examination are important to establish the 
diagnosis and determine the most appropriate treatment.  The treatment algorithm is largely 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 10 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
based on the patient’s level of function, age, comorbidities, size and quality of remaining rotator 
cuff (Tonino, 2009). 
Arthroscopic partial repair, as advocated by Burkhart et al. (Burkhart, 1997) attempts to restore 
function and provide pain reduction.  This approach involves surgical repair utilizing anchors or 
suture placement and requires a protracted period of recovery in order to protect the repair.  
Biomechanical studies have supported such partial repair approaches (Hsu, 2011; Burkhart, 
1997).  
Nevertheless, repair of massive tears is often followed by re-tears, additional muscular 
degeneration, and diminished clinical results over time (Galatz, 2004). Given this, there remains 
a need to evaluate potential alternatives which may prove effective in the treatment of full 
thickness massive rotator cuff tears. 
The study device, the InSpace™ device, is an inflatable biodegradable balloon that is deployed 
arthroscopically into the subacromial space, acting as a spacer, in patients with full thickness 
massive RCTs.  The temporary lowering of the humeral head during spacer inflation may 
additionally provide improved balance between the subscapularis anteriorly and the infraspinatus 
posteriorly, permitting better deltoid activation and compensation. The use of the InSpace device 
may be a simple and less invasive alternative that has the potential to provide comparable safety 
and effectiveness profile to the current, well-established technique of arthroscopic partial repair. 
The purpose of this study is to evaluate the safety and effectiveness of the InSpace device as a 
primary surgical treatment for full thickness massive rotator cuff tears. Secondary aims include 
evaluating additional clinical outcomes and imaging. 
1.2 
Device Name and Intended Use 
The InSpace device under investigation is a biodegradable balloon spacer provided by Ortho-
Space Ltd.  The InSpace device is indicated for the treatment of patients with massive, full-
thickness torn rotator cuff tendons due to trauma or degradation with mild to moderate gleno-
humeral osteoarthritis. 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 11 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
1.3 
Investigational Device 
The InSpace system components are single-use, supplied sterile and ready for use upon removal 
from their package (Figure 1). 
  FIGURE 1: INSPACE SYSTEM COMPONENTS: SPACER (BALLOON),      
                        DEPLOYER AND HANDLE 
 
 
 
 
 
 
 
 
 
 
The InSpace system is comprised of the following components: 
• Biodegradable, Inflatable Spacer (Balloon) 
• Deployer and Handle 
 
The Biodegradable, Inflatable Spacer [(Balloon) – InSpace device] is a single use, 
biodegradable, inflatable spacer (balloon) implant made of Poly (L-lactide-co-ε-caprolactone) 
(Figure 2).  
 
 FIGURE 2: INFLATED INSPACE DEVICE BEFORE AND AFTER SEALING 
 
 
 
 
Deployer and
Protecting Sheath
Biodegradable, Inflatable 
Spacer (Balloon)
Over mold (Stainless Steel) tube and stopper 
 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 12 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
 
The InSpace device is folded inside the outer protecting sheath of the Deployer (Figure 1).  
Through an arthroscopic procedure, following standard debridement/ASD of the shoulder, the 
Deployer is placed in-situ and the InSpace device is positioned in the sub-acromial space 
between the humeral head and the acromion.  The InSpace device is inflated with a physiological 
solution (i.e., saline) and sealed with the plug attached to the tip of the internal inflation tube.  In 
this position, the InSpace device fills the space created by the removal of the bursa thus allowing 
smooth gliding without friction of the humeral head against the acromion (Figure 3).              
The InSpace device degrades within 12 months, a period that may conform well to the 
rehabilitation timeframe following a rotator cuff arthroscopic procedure. 
FIGURE 3: ILLUSTRATION OF THE INSPACE DEVICE PLACED IN THE SUB-ACROMIAL SPACE 
 
 
 
 
 
  The InSpace device has three optional sizes and volume specifications (Table 2). 
TABLE 2: INSPACE DEVICE SIZE AND ASSOCIATED VOLUMES 
Size 
AP 
(mm) 
ML 
 (mm) 
Thickness 
(mm) 
Wall thickness 
(µm) 
Maximal  
volume  to 
spread the 
spacer (cc) 
Recommended 
final inflation 
volume (cc) 
Small 
50 
40 
6 
95-300 
13-15 
9-11 
Medium 
60 
50 
6 
95-300 
20-22 
14-16 
Large 
70 
60 
6 
95-300 
40 
23-25 
 

CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 13 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
The InSpace Deployer and Handle is a single use, deploying system on which the InSpace device 
is loaded.  The Deployer is composed of the following components:  
(1) An ergonomic handle assembly made of biocompatible polycarbonate, white in color with 
red and green color knobs.  The handle serves for the InSpace device insertion and provides the 
sealing mechanism for the InSpace device, positioned and inflated in-situ.  
(2) An external stainless steel overmold tube with plug, mounted on an internal stainless steel 
inflation needle. This component is intended for InSpace device insertion, inflation and sealing 
(Figures 1 and 2). 
(3) A protecting sheath tube that provides the InSpace device external protection while 
performing the arthroscopic placement of the InSpace device in the sub-acromial space. 
1.4 
Regulatory Status and Human Clinical Data  
The InSpace system was CE (Conformité Européenne, 2011) marked in July 2010 and is 
available for distribution throughout Europe.  Since its approval, over two thousand (2000) of the 
InSpace devices were implanted into patients diagnosed with RCT.  
Within these implantations the company received 19 (~1%) complaints of medical events which 
included events such as deterioration in shoulder pain, device displacement, inflammatory 
reaction to the device, and suspected infection.  Although not necessarily related to the device, 
twelve (12) of these events (0.75% 95% exact binomial CI; [0.39% - 1.17%]) required device 
explantation, and nine (9) events (0.56% 95% exact binomial CI; [0.26% - 1.07%]) were 
associated with suspected infection. No events associated with deep joint infections were 
reported. All subjects that underwent explantation of the device were fully recovered following 
the procedure with no further complications.

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 14 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Additional data has been collected in a single center study executed in Slovenia that 
enrolled 24 subjects. Eligible subjects were diagnosed with rotator cuff tears (Senekovic et 
al. 2013). The subjects were divided to two groups – scheduled for repair or un-repairable. 
This study cited no serious adverse device effects (SADE). Significant improvements in 
subjective pain scores commencing at 1 week post-implantation and a decrease in reported 
night pain were observed. Two of the subjects were suspected to have synovitis based on  
Magnetic Resonance (MR) Imaging.  This was considered non-clinically significant and no 
bone formation were observed at the 3-year time point.  
Further to this publication the study was prolonged up to 5 years post-operative follow-up.  
Of 15 subjects who completed the 5 years assessment 86,6% (13/15) maintained an 
improvement of at least 15 points in the TCS with no evidence of Adverse Device Effects. 
A change of over 10 points is considered clinically significant.  
An additional study that was conducted in 5 clinical sites in Israel, 58 subjects diagnosed 
with rotator cuff tear underwent InSpaceTM implantation and were followed for one year 
post implantation. 
Throughout the study the subjects exhibited an improvement from a Total Constant Score 
of 36 at baseline to 64.3 at one year follow up.  
There were two Serious Adverse Device Effects (SADEs) during the course of this study. 
One event resulted in the subject’s hospitalization with antibiotic treatment due to the 
subject’s advanced age (81) and concomitant Diabetes and the other required device 
explanation.  Both events were resolved, one following conservative treatment and the 
other following an additional arthroscopic procedure. 
As the expected range for SADEs following the use of implants in orthopedic surgeries 
ranges from 4% to 19% (Freehill, 2003], the SADE rate presented in this study, which is 
3.45% (95% exact confidence interval: [0.42%-11.99%]) indicates an acceptable risk for 
the implantation and use of the InSpaceTM device.  
There were no unexpected adverse events in this study. All adverse events in the study 
were classified as either mild or moderate with no events classified as severe. Most of 
these events resolved within a few days of initiation, with either conservative treatment: 
medications (mainly analgesics) or observation only.  

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 15 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Adverse Device Effects (ADEs) following implantable orthopedic devices in the shoulder 
are not uncommon and have been reported in up to 47% of the cases (Böstman, 2000, 
Mulieri, 2010]. In this study, 15 out of the 58 subjects (25.86%) reported a total of 20 
ADEs thus the ADE rate is 34.48% (95% exact confidence interval: [22.49%-48.12%]). 
This rate was found to be clinically acceptable for a new implantable device, given the low 
rates of serious, device-related events. 
Following the results of these two studies as well as the experience that was gained in the 
commercial use of over than 2000 implantations in Europe, it can be concluded that the use 
of the Ortho-Space’s InSpace™ device in subjects with rotator cuff tears is a safe and 
effective treatment option associated with early improvement in the TCS and its related 
sub-scores.  
1.5 
Mode of Action 
The following section describes the mode of action of the InSpace device and is supported 
by in-vitro, animal, and human clinical studies. 
Following a standard diagnostic arthroscopy, the InSpace device is positioned, using its 
deployment system, in the sub-acromial space between the humeral head and the acromion. 
Once the deployer tube is placed in-situ the InSpace device is exposed by pulling back the 
protecting sheath (which provides the InSpace device external protection to allow 
arthroscopic placement) and exposing the folded InSpace device. Following removal of the 
protecting sheath the InSpace device is inflated with a physiological solution (i.e. saline) 
and sealed. In this position, the InSpace device fills the space created by the removal of the 
bursa thus allowing smooth gliding without friction of the humeral head against the 
acromion. 
The InSpace device is designed to reduce pain associated with the full thickness MRCTs.  
Because pain associated with a full thickness MRCT may cause abnormal motion, limit 
function and required rehabilitation, quality of life may be greatly impacted.  Breaking the 
pain cycle is intended to allow patients the potential opportunity of temporary pain relief, a 
return to more normal shoulder function, and reduce the need for more invasive procedures 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 16 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
(i.e. reverse total shoulder arthroplasty). This mode of action may lead to an enhanced 
quality of life.  
2 
OVERVIEW OF INVESTIGATIONAL PLAN 
This is a non-inferiority, prospective, single blinded, multi-center, randomized, controlled, 
pivotal study evaluating the safety and effectiveness of the InSpace device as a primary 
surgical treatment for full thickness MRCT in comparison to Partial Repair of a full 
thickness MRCT performed during an arthroscopic procedure. The primary effectiveness 
endpoint is a composite endpoint consisting of four pre-specified components where each 
component must achieve success by Month 12.  In addition, a complete Month 24 analysis 
will be submitted at the conclusion of the study. 
2.1 
    Objectives 
2.1.1 
Primary Objectives 
• To evaluate the safety and effectiveness of the InSpace device as a primary surgical 
treatment for full thickness massive rotator cuff tears  
2.1.2 
Secondary Objectives 
• Change in clinical outcomes compared to baseline 
2.2 
Endpoints 
2.2.1 
Primary Composite Endpoint 
• WORC improvement of 275 points by Week 6 from pre-operative baseline 
and maintained at Month 12 
• ASES improvement of 6.4 points by Week 6 from pre-operative baseline 
and maintained at Month 12 
• No subsequent secondary surgical interventions (SSSI) in the index 
shoulder through Month 12 
• Absence of Serious Adverse Device Effects (SADEs), through Month 12 
 
2.2.2 
Secondary Endpoints 
• Clinical endpoints: 
o Composite endpoint component-level success for WORC compared to baseline 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 17 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
o Composite endpoint component-level success for ASES compared to baseline  
o Change in Western Ontario Rotator Cuff Index (WORC) questionnaire scores from 
baseline 
o Change in American Shoulder and Elbow Surgeons (ASES) from baseline 
o Change in Constant-Murley Shoulder Outcome Score from baseline 
o Change in EuroQOL five dimensions questionnaire (EQ-5D-5L) from baseline 
o Change in Visual Analogue Scale (VAS) scores from baseline 
o Change in Range of Motion (ROM) from baseline 
o Composite endpoint success at Month 24 
• Imaging endpoints will include reading of MRI scans conducted at 
o Week 6 post treatment to assess (Group I: InSpace device [includes only 
subjects enrolled under Protocol V3.0, May 1, 2017]):  
▪ device location in the sub-acromial space 
o Month 12 post treatment to assess (all randomized subjects): 
▪ the device residuals (Group I – InSpace only)  
▪ the shoulder joint and surrounding tissue condition (Group I: 
InSpace device and Group II: Partial Repair)  
 
2.2.3 
Safety Assessment 
Safety will be evaluated by type, frequency, severity, and relatedness of adverse events to 
study treatment and control treatment. 
3 
PROTOCOL 
3.1 
Study Design 
This is a non-inferiority, prospective, single blinded, multi-center, randomized, controlled, 
pivotal study. The study is designed to evaluate the safety and effectiveness of the InSpace 
device as a primary surgical treatment for a full thickness MRCT in comparison to Partial 
Repair of a full thickness MRCT performed during an arthroscopic procedure.  
 
The study will enroll 184 subjects presenting with a full thickness MRCT.  These 184 
subjects will be randomized 1:1, producing approximately 92 subjects randomized to the 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 18 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Study Treatment: Group I- InSpace device and 92 randomized to the Control Treatment: 
Group II – Partial Repair. 
Pharmacoeconomic data such as the subject’s bills relating to the surgical procedure (i.e., 
operating room time, length of stay, medications, research center visits, rehabilitation and 
other related procedural costs) will be collected at the follow-up visits, if applicable.  In 
addition, procedural and diagnostic codes, and reimbursement information may be 
collected.  Analysis of these data should allow a comparison of the net costs and net 
benefits of the study treatment to the control treatment.  These economic endpoints will not 
be included in the data set for FDA submission because they do not relate to device safety 
or effectiveness. 
3.2 
Subject Recruitment and Screening 
Subjects will be voluntarily recruited from the Principal Investigator or Sub-Investigator 
population and/or referring physicians. 
Subjects who present with a full thickness MRCT will be screened to determine if they 
meet all inclusion and no exclusion criteria. If all entry criteria are achieved, the subject 
will be eligible to participate in the study. All general and indication-specific entry criteria 
must be met prior to study entry.  
All potential subjects screened for eligibility will be listed on the Screening and 
Enrollment Log. The Screening and Enrollment Log will document the date of screening, 
the results of screening, and the primary reason for excluding the subject (e.g., does not 
satisfy eligibility criteria or subject declined). 
Subjects who are eligible to enter the study will be provided with an Institutional Review 
Board (IRB) or a Research Ethics Board (REB) approved Informed Consent Form (ICF) 
for review and signature. Each subject will have a physical exam of the index shoulder that 
incorporates a medical history and injury etiology.  Diagnosis of the rotator cuff tear will 
be confirmed with MRI acquired within 9 months of enrollment. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 19 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.3 
Study Blinding 
The Investigator and surgical attendees will be unblinded to the treatment assignment due 
to the nature of the surgical procedure and post-op rehabilitation process.  
The subject will remain blinded to the treatment assignment until completion of the study.  
See section 5.4 for Unblinding Procedures. 
3.4 
Study Duration and Follow-up 
The anticipated study duration is 48 months, which includes an approximate 24 month 
enrollment period and 24 month follow-up period.  
Subjects will be assessed pre-operatively and at Day 10, Week 6, and Months 3, 6, 12, and 
24 post-operatively. At each follow-up visit, a shoulder examination will be performed, 
subject questionnaires will be administered, and Adverse Events (AEs) and concomitant 
medication will be reviewed, if applicable. All study treatment arm subjects (Group I: 
InSpace device [includes only subjects enrolled under Protocol V3.0, May 1, 2017]) will 
receive an MRI at Week 6 to assess device location. 
At Month 12 post-operatively, all randomized subjects will complete a MRI scan of the 
treated shoulder.  
The Study Flowchart and Follow-Up Assessments table (Table 1) outlines study 
procedures and timelines. 
3.5 
Randomization 
Centralized randomization will be performed, and subjects will be randomly assigned to 
one of the following groups by a 1:1 schema: 
• Group I: InSpace device 
• Group II: Partial Repair  
3.6 
Selection of Subjects 
Subjects who meet all of the following criteria will be voluntarily recruited by participating 
Investigators: 
3.6.1 
Inclusion Criteria 
Subjects MUST meet ALL of the following criteria to be included in the study: 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 20 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
1. The subject has signed the IRB/REB approved Informed Consent Form (ICF) 
specific to this study prior to enrollment 
2. Is male or female ≥ forty (40) years of age 
3. Positive diagnostic imaging by MRI within 9 months of enrollment of the index 
shoulder indicating a full thickness MRCT: 
a. measuring ≥ 5 cm in diameter (Cofield classification) 
b. involving ≥ two tendons 
4. Functional deltoid muscle and preserved passive range of motion on physical 
examination 
5. Documented VAS score of  >30 mm pain  
6. Failed non-operative treatment of at least 4 months from the initial treatment to 
include one or all of the following: 
a. Oral analgesics 
b. Anti-inflammatory medication (e.g., ibuprofen, naproxen) 
c. Corticosteroid injection(s) 
d. Physical therapy 
e. Activity modification 
f. Rest (sling used) 
7. Must be able to read and understand the approved Informed Consent Form 
(written and oral) 
8. Must be in general good health (as determined by the Investigator) based on 
screening assessments and medical history 
9. Must be independent, ambulatory, and can comply with all post-operative 
evaluations and visits. 
 
3.6.1.1 Intra-operative Inclusion Criteria 
Subjects MUST meet the following criteria to be randomized in the study: 
• Full thickness tear  
• Tear size ≥5 cm in diameter (Cofield classification) 
• Tear involving ≥ two tendons 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 21 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.6.2 
Exclusion Criteria 
Subjects will be excluded from the study, if they meet ANY one (1) of the following 
criteria:  
 
1. Known allergy to the device material (copolymer of PLA and -ε-caprolactone) 
2. Evidence of the following conditions: 
a. severe gleno-humeral or acromiohumeral arthritis 
b. full thickness cartilage loss as seen on MRI 
c. history within the past 5 years of anterior or posterior shoulder subluxation or 
dislocation as determined by history, examination or radiographic findings 
d. pre-existing deltoid defect or deltoid palsy 
e. major joint trauma, infection or necrosis 
f. partial thickness tears of the supraspinatous 
g. fully reparable rotator cuff tear [Tear of less than 5 cm in diameter (or < 4 cm2) 
with retractable tendon that can be fully repaired] 
h. known neurovascular compromise 
i. complete deltoid muscle palsy 
j. traumatic muscle tears of the pectoralis or deltoid 
3. The subject requires concomitant: 
a. subscapularis repair 
b. labral repair of any type 
4. Previous surgery of the index shoulder in the past 1 year, excluding diagnostic 
arthroscopy 
5. The subject’s condition is bilateral and rotator cuff repair is scheduled or to be 
scheduled over the course of this study for the contra lateral shoulder 
6. Major medical condition that could affect quality of life and influence the results of the 
study (e.g. HIV or other immunosuppressive conditions, active malignancy in the past 
5 years, acute MI, CVA, etc.)   
7. The subject has documented evidence of a history (e.g., liver testing) of drug/alcohol 
abuse within12 months of enrollment 
8. The subject’s condition represents a worker’s compensation case 
9. The subject is currently involved in a health-related litigation procedure  

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 22 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
10. Females of child-bearing potential who are pregnant or breastfeeding or plan to become 
pregnant during the course of the study 
11. Concurrent participation in any other investigational clinical study one month prior to 
enrollment or during the entire study period 
12. The subject has implanted metallic devices (e.g., cardiac pacemakers, insulin pumps, 
nerve stimulators), medically implanted clips or other electronically, magnetically or 
mechanically activated implants that would contraindicate undergoing a MRI scan of 
the index shoulder  
13. The subject has claustrophobia that would inhibit their ability to undergo a MRI scan 
of the index shoulder  
14. The subject is physically or mentally compromised (e.g., currently being treated for a 
psychiatric disorder, senile dementia, Alzheimer’s disease, etc.), to the extent that the 
Investigator judges the subject to be unable or unlikely to remain compliant to follow-
up 
15. The subject is receiving prescription narcotic pain medication for conditions unrelated 
to the index shoulder condition 
16. The subject currently has an acute infection in the area surrounding the surgical site. 
17. Baseline WORC score less than 420. 
3.6.2.1 Intra-operative Exclusion Criteria 
Subjects will not be randomized and will be terminated from the study if they meet 
any one (1) of the following intra-operative exclusion criteria: 
• Rotator cuff is/presents with: 
o fully reparable with adequate tissue quality (equivalent to Goutallier 
stage 1 or 2) 
o partial thickness tear of the supraspinatous 
o evidence of significant osteoarthritis  
• The subject requires concomitant: 
o subscapularis repair 
o labral repair of any type 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 23 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Coracoacromial ligament functional deficiency is identified 
• Partial repair requires any type of grafting for enhancement of the partial repair 
procedure 
3.7 
Early Withdrawal of Subjects 
3.7.1 
When and How to Withdraw Subjects 
Subjects may voluntarily withdraw from the study at any time for any reason. The 
Investigator(s) may elect at any time to withdraw a subject from the study for any reason 
unrelated to the study if such a decision is in the subject’s best medical interest. Subjects 
who experience an AE may also voluntarily withdraw or be withdrawn if deemed in the 
subject’s best medical interest. Subjects with a secondary surgical intervention to the index 
shoulder will also be discontinued in the study.  If a subject discontinues the study 
prematurely or is withdrawn by the Investigator(s), data collected up to the time of 
withdrawal will be used, if applicable, for analysis. The primary reason for termination or 
discontinuation will be documented on the End of Study case report form (CRF). Subjects 
who are withdrawn following randomization for any reason from the study will not be 
replaced. 
3.7.2 
Data Collection and Follow-up for Withdrawn Subjects 
Subjects who withdraw consent and refuse to complete the follow-up assessments, fail to 
adhere to protocol requirements, or die during the follow-up phase will be considered end 
of study at that time. Attempts will be made to retrieve any follow-up data, in particular, 
regarding possible AEs at the time of study discontinuation. If the Investigator(s) reports a 
subject as lost to follow-up, the Clinical Research Associate (CRA) will ensure that the 
designated study staff has documented the reason(s) this occurred and has ensured that 
every attempt was made by the Investigator(s) to contact the subject to determine subject 
status. Appropriate documentation will consist of at least two documented attempts at 
contact via telephone, followed by an attempt to contact via a registered US/Canada post 
letter. 
3.7.3 
Study Site Termination 
A specific study site in this multi-center study may also warrant termination under the 
following conditions: 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 24 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Failure of the Investigator to enroll subjects into the study at an acceptable rate; 
• Failure of the Investigator to comply with Food and Drug Administration (FDA) 
and Health Canada (HC) regulations, the International Conference on 
Harmonization (ICH) guidelines, IRB/REB policies and procedures; 
• Knowingly submitting false information from the study site to the Sponsor or its 
designee, IRB/REB, and/or regulatory body(s), as applicable; or 
• Insufficient adherence to protocol requirements. 
Study termination will be performed in compliance with the Sponsor’s standard 
procedures. 
3.8 
Prior and Concomitant Therapy 
Information on concomitant medications used will be recorded on the Concomitant 
Medication CRF.  Any ongoing medication used by the subject within 4 months of 
enrollment will be considered concomitant medication (e.g., aspirin, Tylenol, vitamins, 
dietary supplements, etc).  Any changes in medication must be noted on the Concomitant 
Medication CRF.  
Any other investigational drug or approved therapy for investigational use is not permitted 
during study participation.   
3.9 
Study Interventions – Full Thickness MRCT 
A diagnostic arthroscopic evaluation will be conducted to confirm the diagnosis of full 
thickness MRCT. Once intra-operative eligibility is confirmed, the subject will be 
randomized to receive one of the following treatments:  
• Group I – InSpace device 
• Group II – Partial Repair 
 
3.9.1 
Clinical and Functional Assessments 
All subjects will be clinically evaluated by the Investigator or a qualified individual noted 
on the Delegation of Authority (DOA) log.  Clinical and functional assessments will be 
measured as noted below: 
• Western Ontario Rotator Cuff Index (WORC): a subject self–report questionnaire 
that is a disease-specific Quality of Life Measurement Tool specifically designed to 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 25 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
evaluate quality of life in persons with pathology of the rotator cuff. It is comprised 
of 21 items in 5 domains (i.e., physical symptoms, sports and recreation, work, 
lifestyle, emotions). 
• American Shoulder and Elbow Surgeons (ASES): a subject self-report 
questionnaire and Investigator assessment questionnaire.  The subject portion 
collects information on pain (i.e., 5 questions plus a VAS), instability (using a 
VAS) and activities of daily living (i.e., 10 questions). The MCID for the ASES has 
been determined to be 6.4 points, which is the value that is associated with the 
patient’s perception of meaningful change (Michener LA, 2002).  The Investigator 
assessment portion documents ROM, signs, strength, and instability. 
• Constant-Murley Shoulder Outcome Score: performed by the Investigator or 
designee to assess the shoulder and determine at minimum the ROM, external 
rotation and internal rotation, and power score.  
•  EuroQOL five dimensions questionnaire (EQ-5D-5L): a subject self-report 
questionnaire to measure health-related quality of life (HRQOL). It consists of 5 
questions capturing the subject’s current health across five dimensions (i.e., 
mobility, self-care, usual activities, pain/discomfort and anxiety/depression). It also 
includes a numerical visual analogue scale (EQ-VAS). 
• Visual Analogue Scale (VAS): a subject self-report questionnaire to measure pain. 
The patient marks on the line the point that they feel represents their perception of 
their current state.  The amount of pain that a patient feels ranges across a 
continuum from none to an extreme amount of pain. 
 
3.9.2 
Magnetic Resonance Imaging (MRI) 
At Week 6 post-operatively, all study treatment arm subjects (Group I: InSpace device 
[includes only subjects enrolled under Protocol V3.0, May 1, 2017]) will receive an MRI 
to assess device location. 
Week 6 post-operative MRI assessments will consist of reads completed by an un-blinded 
radiologist(s) 
• Group I: InSpace device 
o to assess the device location in the sub-acromial space 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 26 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
At Month 12 post-operatively, all randomized subjects will complete a MRI scan of the 
treated shoulder.  
Month 12 post-operative MRI assessments will consist of reads completed by blinded  
radiologist(s).   
The following MRI scans reads will be performed at Month 12 for the Study  
• Group I: InSpace device 
o to assess the device residuals at Month 12 post treatment 
o to assess the shoulder joint and surrounding tissue condition at Month 12  
post treatment 
• Group II: Partial Repair 
o to assess the shoulder joint and surrounding tissue condition at Month 12 
post treatment    
3.9.3 
Ultrasound 
The first fifteen (15) study treatment arm subjects received an ultrasound to measure 
device position. Ultrasound was performed at Visit 3, 4 and 5 post implantation. The 
ultrasound series is now complete. 
3.10 Visit Summary 
3.10.1 Visit 1:  Screening/Baseline (days - 45 to - 1) 
All potential subjects screened for eligibility will be listed on the Screening and 
Enrollment Log. The Screening and Enrollment Log will document the date of screening, 
the results of screening, and the primary reason for excluding the subject (e.g., does not 
satisfy eligibility criteria or subject declined). 
Qualified subjects who agree to participate in the study will be required to sign an IRB/ 
REB approved ICF.  After signing the IRB/ REB approved ICF, study subjects will 
undergo study-specific procedures and the following activities will be performed.  
• Clinical Assessment: 
Data collected will include but not be limited to: 
• Confirm written informed consent, prior to any screening procedures 
• Eligibility criteria verification (inclusion/exclusion criteria) 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 27 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Medical and surgical history 
• Previous non-operative treatment 
• Demographics (e.g., age, sex, date of birth, height, weight) 
• Work status, living environment, nicotine use 
• Concomitant medication, if applicable 
• Mechanism of injury, if applicable 
• Screening number assignment 
• Confirm Visit 2 (surgery) scheduled within 45 days after screening 
• Evaluation Assessment: 
Data collected will include, but is not limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES   
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
Pre-operative imaging includes (within 9 months of enrollment): 
• MRI 
3.10.2  Visit 2: Surgery: (day 0) 
If the Investigator(s) discovers the presence of a condition at the time of the procedure that 
would render the subject ineligible for study participation, the subject should be considered 
as an intra-operative failure and be discontinued from the study.  The subject should 
receive the standard of care as determined by the Investigator(s).   
The primary reason for termination or discontinuation will be documented on the End of 
Study CRF. 
If the subject continues to meet eligibility criteria the information collected will include, 
but not be limited to: 
• Date of surgical procedure 
• Randomization assignment 
• Anesthesia type, time 
• Operating room times, procedure times 
• Product related information 
• AEs 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 28 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Concomitant medications 
For females of child-bearing potential, a pregnancy test, urine or blood, will be performed 
no earlier than 2 days before the scheduled surgical procedure, if applicable. 
3.10.2.1 Intra-operative Procedure 
• Randomization  
• If the subject continues to meet all of the intra-operative inclusion and none 
of the intra-operative exclusion they will be randomized to receive one of 
the following: 
▪ Group I: InSpace Device 
▪ Group II: Partial Repair 
• Intra-operative Inclusion Criteria 
Subjects MUST meet the following criteria to be randomized in the study: 
• Full thickness tear  
• Tear size ≥5 cm in diameter (Cofield classification) 
• Tear involving ≥ two tendons 
• End of Study – Intra-operative Exclusion 
Subjects will not be randomized and be considered end of study if they meet any one 
(1) of the following intra-operative exclusion criteria: 
• Rotator cuff is/presents with: 
o fully reparable with adequate tissue quality (equivalent to Goutallier 
stage 1 or 2) 
o partial thickness tear of the supraspinatous 
o evidence of significant osteoarthritis  
• The subject requires concomitant: 
o subscapularis repair 
o labral repair of any type 
• Coracoacromial ligament functional deficiency is identified 
• Partial repair requires any type of grafting for enhancement of the partial repair 
procedure 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 29 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
In case of intra-operative failure the subject will not be randomized into the study and will 
not be counted as a recruited subject (will be replaced with a new subject).  
3.10.3 Visit 3:  Day 10 Follow-Up (+/- 6 days)  
• Admission/Discharge information  
• Length of stay 
• Evaluation Assessment: 
Data collected will include, but is not limited to: 
• ASES - Shoulder examination  
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
 
3.10.4 Visit 4:  Week 6 Follow-Up (+/- 7 days) 
• Evaluation Assessment: 
Data collection and procedures will include but not be limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES - Shoulder examination  
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
• Compliance with Post-operative Rehabilitation Guideline 
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
Post-operative imaging includes: 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 30 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Week 6 MRI scan to all study treatment arm subjects (Group I: InSpace device 
[includes only subjects enrolled under Protocol V3.0, May 1, 2017])  
3.10.5 Visit 5: Month 3 Follow-Up (+/- 14 days) 
• Evaluation Assessment: 
Data collection and procedures will include but not be limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES - Shoulder examination  
• Assessment of evidence of infection (warmth, swelling, skin changes) 
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
Each subject will be asked to complete the following subject self-report questionnaire 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
 
3.10.6  Visit 6: Month Follow-Up (+/-14 days) 
• Evaluation Assessment: 
Data collection and procedures will include but not be limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES - Shoulder examination  
• Assessment of evidence of infection (warmth, swelling, skin changes) 
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 31 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.10.7 Visit 7: 12 Month Follow-Up (+/-1 month) 
• Evaluation Assessment: 
Data collection and procedures will include but not be limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES - Shoulder examination  
• Assessment of evidence of infection (warmth, swelling, skin changes) 
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
Post-operative imaging includes: 
• Month 12 MRI scan to all randomized subjects (Both Arms)  
3.10.8 Visit 8: Month 24 Follow-Up (+/-2 months) 
• Evaluation Assessment: 
Data collection and procedures will include but not be limited to: 
• Constant-Murley Shoulder Outcome Score 
• ASES - Shoulder examination  
• Assessment of evidence of infection (warmth, swelling, skin changes) 
• AEs, if applicable 
• Concomitant medication, if applicable 
o Any changes in concomitant medication 
Each subject will be asked to complete the following subject self-report questionnaires 
following the shoulder examination: 
• WORC 
• EQ-5D-5L 
• ASES 
• VAS 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 32 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.10.9 Optional Follow-Up Visit, Unscheduled Visit Procedures  
Subjects that have pre-scheduled surgical visits not involving the index or contralateral 
shoulder (e.g., gallbladder removal, knee arthroscopy), and subjects that have additional 
visits beyond the study-scheduled visits and within the standard of care do not need 
documentation, unless associated with an AE (e.g., generalized AE or device/treatment-
related AE). 
3.10.10 Post-operative Rehabilitation Guideline 
Recommended guidelines for post-operative rehabilitation are included for consistency in 
procedures across all study sites (Appendix I). 
3.11 Receiving, Storage, Dispensing and Return of Investigational Product 
3.11.1 Receipt and accountability 
The InSpace device will be shipped directly to each study site from Ortho-Space Ltd., or 
designated affiliate. 
The Principal Investigator is responsible for ensuring that accurate records are maintained 
for the receipt and dispensing of all investigational devices, including dates and number of 
investigational devices received, to whom dispensed (subject-by-subject accounting), and 
accounts of any investigational devices accidentally or deliberately destroyed.  Upon 
receipt of the shipment, inventory will be performed and an accountability log completed 
and signed by the person accepting the shipment.  The designated study staff will count 
and verify that the shipment contains all the items noted on the shipment inventory list.   
Any damaged or unusable investigational device in a given shipment will be documented.  
The Investigator or designee must notify the Sponsor of any damaged or unusable 
investigational devices supplied to the investigator’s site. Peel-off labels on the InSpace 
device package are to be placed in the chart / source documents.  These records must be 
readily available for inspection by the Sponsor or designee (if applicable) during routine 
site monitoring visits and are open to regulatory authority inspection at any time.  The 
Investigator may dispense investigational devices(s) only to subjects who have enrolled in 
the study and have signed the IRB/REB approved ICF. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 33 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
3.11.2 Storage 
Until use, the InSpace device should be stored in a secured, clean, and dry area with a 
maintained temperature of 0-29°C (32-84.2°F) degrees.   
3.11.3 Dispensing of Investigational Device 
One (1) InSpace device will be implanted per subject according to the randomization 
assignment. It may be necessary to dispense three (3) InSpace devices to the operating 
room due to sizing availability. Reconciliation will be performed to document date used or 
destroyed, subject assignment, and investigational device balance.  This reconciliation will 
be documented on the accountability log, signed and dated by the study staff.  Any 
discrepancies noted will be documented, investigated, and resolved.   
3.11.4 Return or Destruction of Investigational Product 
Unless otherwise specified, all unused investigational devices must be saved for 
accountability purposes and returned to the Sponsor or designated affiliate.  A copy of the 
accountability log must be forwarded to the Sponsor or designated affiliate with the 
returned or defaced investigational devices (as applicable). 
4 
STATISTICAL ANALYSIS 
This section presents general information about statistical considerations and concepts 
such as randomization, stratification, statistical power, sample size, and a brief discussion 
on analysis methodology, as well as some data conventions. Detailed descriptions of the 
statistical analysis methods and data conventions will be in a separate document; i.e., the 
Statistical Analysis Plan (SAP). 
4.1 
Treatment Groups  
The following treatment groups will be assessed: 
Arm 
Description 
Study Treatment 
Group I: InSpace device 
Control Treatment 
Group II: Partial Repair 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 34 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.2 
Description of Study Endpoints  
4.2.1 
Primary Composite Endpoint 
The primary composite endpoint has four components as follows: 
• WORC improvement of 275 points by Week 6 from pre-operative baseline 
and maintained at Month 12 
• ASES improvement of 6.4 points by Week 6 from pre-operative baseline 
and maintained at Month 12 
• No subsequent secondary surgical interventions (SSSI) in the index 
shoulder through Month 12 
• Absence of Serious Adverse Device Effects (SADEs), through Month 12 
 
The first component of the composite endpoint is a clinical measure.  WORC is a validated 
and reliable disease-specific quality of life index that assesses multiple domains with 
twenty-one (21) questions from five (5) domains that are scored with use of a 100-mm 
VAS. The total score ranges from 0 to 2100, with higher scores indicating a worse 
outcome. Results from Kirkley et al. (2003) and Ekeberg et al. (2010) have established a 
minimal important change of less or equal to 275 WORC points.  In this study, we use the 
mean difference for a component of the composite endpoint with success declared when a 
275-point improvement from pre-operative baseline is achieved by Week 6 and maintained 
at Month 12.   
The second component is an improvement in pain and function.  The American Shoulder 
and Elbow Surgeons Assessment Form (ASES) was developed as a standardized 
assessment of shoulder function (Richards RR, 1994).  The ASES patient self-reported 
section, consists of 2 dimensions: pain and activities of daily living (function).  The pain 
score is determined from a single pain question, and the function score from the sum of 10 
questions specific to activities of daily living. In this study, for a component of the 
composite endpoint we use the mean difference with success declared if a 6.4-point 
improvement in the ASES computed score from pre-operative baseline is achieved by 
Week 6 and maintained at Month 12.  This aligns with the ASES MCID determined by 
Michener et al. (2002).    

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 35 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
The third component is the absence of any subsequent secondary surgical interventions 
(SSSI) in the index shoulder through Month 12. 
The fourth component is the Absence of Serious Adverse Device Effects (SADEs), 
through Month 12. 
 
4.2.2 
Secondary Endpoints 
Clinical Endpoints: 
• Composite endpoint component-level success for WORC compared to baseline 
• Composite endpoint component-level success for ASES compared to baseline 
• Change in Western Ontario Rotator Cuff Index (WORC) questionnaire scores from 
baseline. Mean and percent changes as well as the corresponding standard 
deviations will be calculated. 
• Change in American Shoulder and Elbow Surgeons (ASES) from baseline. Mean 
changes and standard deviations will be calculated. 
• Change in Constant-Murley Shoulder Outcome Score from baseline.  Mean 
changes and standard deviations will be calculated. 
• Change in EuroQOL five dimensions questionnaire (EQ-5D-5L) from baseline. 
Mean changes and standard deviations will be calculated. 
• Change in Visual Analogue Scale (VAS) scores from baseline. Mean changes and 
standard deviations will be calculated. 
• Change in Range of Motion (ROM) from baseline. Mean changes and standard 
deviations will be calculated. 
• Composite endpoint success at Month 24 
o Imaging endpoints will include reading of MRI scans conducted at: 
o Week 6 post treatment to assess (Group I: InSpace device [includes only 
subjects enrolled under Protocol V3.0, May 1, 2017]): 
▪ device location in the sub-acromial space 
o Month 12 post treatment to assess (all randomized subjects): 
▪ the device residuals (Group I – InSpace only)  
▪ the shoulder joint and surrounding tissue condition (Group I: 
InSpace device and Group II: Partial Repair)  
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 36 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.2.3 
Safety Assessments  
Safety will be assessed by monitoring the Adverse Events and tolerance post treatment, as 
detailed in SAFETY AND ADVERSE EVENTS section of this protocol.  
Safety will be evaluated by type, frequency, severity, and relatedness of adverse events to 
study treatment and control treatment. 
 
4.2.4 
Radiographic Assessments  
In the first year after surgery, the radiological assessment of the rotator cuff will serve as a 
supportive marker to establish the efficacy for the study success (based on the clinical 
evaluation of the index shoulder). 
Shoulder MRI will be conducted per imaging acquisition guidance (Appendix C) in the 
following visits: 
• Visit 1 (Screening/Baseline): All Subjects (Both Arms): Pre-operative baseline 
MRI scan within 9 months of enrollment. 
• Visit 7 (12 Month Follow-Up): All Subjects (Both Arms):  
Group I: InSpace device 
• to assess the device residuals at 12 months post implantation 
• to assess the shoulder joint and surrounding tissue condition at 12 months post 
implantation.    
Group II: Partial Repair 
• to assess the shoulder joint and surrounding tissue condition at 12 months post 
implantation.    
Additionally, at Week 6 all study treatment arm subjects (Group I: InSpace device 
[includes only subjects enrolled under Protocol V3.0, May 1, 2017]) will receive an MRI 
to assess the device location in the sub-acromial space. 
Shoulder MRI will be conducted per imaging acquisition guidance (Appendix H) in the 
following visit: 
• Week 6 (Group I: InSpace device [subjects enrolled under Protocol V3.0, May 1, 
2017]) 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 37 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
In addition, at any stage during the follow up period, if deemed necessary by the 
Investigator, (due to clinical symptoms such as suspected infection, suspected device 
displacement associated with deterioration in shoulder function or symptomatic re-tear of 
the repaired rotator cuff) shoulder radiography (X-Ray), ultrasound or MRI may be 
performed to confirm shoulder condition or any surgery associated adverse effects. 
Imaging results will be assessed by independent certified radiologist. 
4.3 
Hypotheses 
The null hypothesis is that there is at least a 10% disadvantage in the composite success 
percent for InSpace vs. Partial Repair Control while the alternative hypothesis is that there 
is less than a 10% disadvantage for InSpace (PT) vs. Partial Repair Control (PC). 
 
H0:  PT – PC ≤ -10%  
versus 
 
HA:  PT – PC > -10%. 
The non-inferiority design allows a penalty-free test for superiority in the event that non-
inferiority is established (one-sided p≤0.025).  Non-inferiority will rule out the 10% non-
inferiority margin favoring InSpace while superiority will need to rule out a 0% margin 
favoring InSpace.  
This sequential hypothesis testing has the Type I error rates for both the non-inferiority and 
superiority controlled at one-sided 2.5% Type 1 error with superiority to be tested after 
non-inferiority as:    
H0: PT ≤ PC   
versus    
HA: PT > PC, 
4.4 
Sample Size Determination and Rationale 
A total of 184 subjects (92 subjects per group) will be randomized to ensure that at least 
166 subjects (83 subjects per group) complete the study; it is assumed that 10% will be 
excluded.  The hypothesis testing will be one-sided with 2.5% Type I error to test non-

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 38 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
inferiority with 80% power.  The null hypothesis of a 10% absolute disadvantage vs Partial 
Control will be tested against a 10% absolute advantage vs. Partial Control for the purpose 
of sample size justification.   
Table 1.A.1 displays the sample size for various surgical control success percents 
ranging from 50% to 62.5% for the composite endpoint; this will be adjusted at the 
interim analysis.  The 50% success percent is the worst case and will decrease as the 
success rate deviates from 50%; the sample size would increase to 180 from 166.          
 
Table 1.A.1: Lower 97.5% confidence limit to rule out 10% N-I margin for success % 
differences: 80% power 
1 
2 
3 
 Partial Repair success %, PC 
0.500 
0.600 
0.625 
 InSpace success % expected, PT 
0.600 
0.700 
0.725 
 Lower limit for PT – PC, LL 
-0.100 
-0.100 
-0.100 
 Power (%) 
80 
80 
80 
 n per group 
90 
85 
83 
 
Table 1.A.2 presents the corresponding InSpace success percents that would achieve 
statistical significance to rule out a 10% disadvantage.  For 166 completers, a 3.8-4.2% 
InSpace advantage is needed (Columns 1-2).   
 
Table 1.A.2:  Lower 97.5% confidence limit to rule out 10% N-I margin for success % 
difference: One-sided p=0.025 
1 
2 
3 
 
 
 
 Partial Repair success %, PC 
0.500 
0.600 
0.625 
 
 
 
 InSpace success % expected, PT 
0.538 
0.641 
0.6667 
 
 
 
 Lower limit for PT – PC, LL 
-0.100 
-0.100 
-0.100 
 
 
 
 n per group 
90 
85 
83 
 
 
 
 
Table 1.A.3 presents the corresponding InSpace success percents that would achieve 
superiority.  A 14-14.2% InSpace advantage is needed (Columns 1-2).   
 
  Table 1.A.3:  Lower 97.5% confidence limit to establish superiority for success % 
difference: One-sided p=0.025 
1 
2 
3 
 
 
 
 Partial Repair success %, PC 
0.500 
0.600 
0.625 
 
 
 
 InSpace success % expected, PT 
0.642 
0.74 
0.764 
 
 
 
 Lower limit for PT – PC, LL 
0.000 
0.000 
0.000 
 
 
 
 n per group 
90 
85 
83 
 
 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 39 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
 
4.5 
Randomization 
This is a non-inferiority prospective, single blinded, multi-center, randomized, pivotal study. 
The randomization will be central and use a mixed block size with a 1:1 ratio of study 
treatment group to control treatment group. 
An individual independent of the study execution team will develop the randomization 
schedule. Subjects who have met all of the inclusion and none of the exclusion criteria, who 
have provided written informed consent will be randomly assigned to the study treatment 
group or the control treatment group based on this randomization schedule. The 
randomization assignment will be made through an Interactive Web Randomization System 
(IWRS).   
4.6 
Stratification and Site Blocking 
Stratification is used to assure a within-stratum-balanced distribution of subjects between 
the two groups. Prior to randomization, subjects will be stratified based on gender and site. 
4.7 
Blinding 
4.7.1 
Study Blinding 
The study will remain blinded until all subjects complete the Month 12 evaluation.  The 
Month 12 report will contain all effectiveness results including clinical, imaging, and 
safety data. 
 
4.7.2 
Subject Blinding 
Subjects will be blinded to treatment assignment until the completion of the study.  All 
efforts will be made to keep the subject blinded through Month 24.  Should a subject 
undergo subsequent arthroscopy for recurrent or new symptoms, withdraw from the study, 
or be terminated from the study, the blinded assignment will be revealed to the subject and 
the Investigator will provide care as standard and usual. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 40 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.8 
Interim Analysis (IA) 
An Interim Analysis (IA) will be conducted when approximately 80 per-protocol subjects 
(~40 per treatment group) have been randomized and completed the Month 12 post-treatment 
follow-up.  Only subjects completing the Month 12 post-treatment follow-up, including early 
withdrawals, will be included in the interim analysis. 
The procedures for this IA will be based on a standard operating procedure (SOP) that has a 
well-established firewall to protect the integrity of the study, and the Type I Error rate will be 
adjusted to maintain the Trial-wise Error rate. The IA will be performed by an unblinded 
statistician, who is not otherwise associated with the conduct of this study. The IA will be 
conducted under the auspices of an independent Data Safety Monitoring Board (DSMB).  
The objectives of this initial IA are to apply a promising zone methodology to make the 
following decisions: 
• Re-assess sample size to evaluate the sample size estimations, which will serve in the 
planning of the remaining study. An unblinded statistician will conduct the power 
analyses. 
• Assess futility of continuing the study based on the interim data. 
 
The study will not be stopped for superiority.  
 
4.8.1 
Procedures for Interim Analysis  
• Cutoff dates for collection of CRFs, data cleaning, database lock and analysis is 
established based on an estimated target date of the 80th treated subject per protocol 
completing the Month 12 post treatment follow up.    
• All data received by the cutoff date is entered, validated, queries generated and 
resolved or pending queries documented.   
• The database is locked for the IA.  
• The locked database is saved in a drive to which only the unblinded statistician 
responsible for the IA has access. 
Using this data, the unblinded statistician will prepare safety summaries and calculate the 
following metrics for the primary endpoint: 
1. Composite success percents (Pt and Pc) at Month 12. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 41 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
2. The dropout rate at the time of the IA. 
3. The Conditional Power (CP) Analysis of the study at the time of the IA (Chen, 
2004). (The method for this calculation is provided in the paragraph below). 
4. The revised sample size requirement based on this IA (The rule and method for 
sample size recalculation and p-value adjustment are provided below). 
4.8.2 
Conditional Power Calculation 
The CP will be calculated according to the below formula (Chen, 2004) using the Month 
12 success percents for the study treatment group to control treatment groups  
CP (f1,z1) = Φ { z1 / 
   –   zα  / 
 } 
Where: 
• CP(f1,z1)  is the conditional power at the IA  
• Φ{.} is the cumulative distribution function of a standard Normal distribution 
(μ=0, σ2 = 1)  
• f1 is the fraction of patients enrolled and used in the IA before decision of 
increasing the sample size  
• zα is the upper α bound for standard Normal distribution  
• z1 is the standardized Normal, since the primary endpoint is based on 
proportions the z-score will be obtained from the following formula:  
z1 = ((pt – pc - δ)/√((pt(1-pt)/nt) + (pc(1-pc)/nc))  
Where: 
o pt = the Composite success percent at Month 12 for the subjects in the study 
treatment group    
o pc = the Composite success percent at Month 12 for the subjects in the control 
treatment group  
o pt(1-pt) = the standard deviation for the subjects in the study treatment 
group 
o pc(1-pc) = the standard deviation for the subjects in the control 
treatment group 
o nt = the number of subjects in the study treatment group used in the IA 
o nc = the number of subjects in the control treatment group used in the IA 
o t = the InSpace group 
o c = the Control group 
The resulting CP will be used to determine whether the sample size needs to be 
increased or remain unchanged. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 42 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.8.3 
Rules and Method for Increasing Sample Size  
Rules:  
• If the conditional power at the time of the interim analysis is < 10% then the study 
will be terminated for futility.  
• If the conditional power is >= 10% but <36%, then the sample size will not be 
increased and the study will continue based on the original sample size.  
• If the conditional power is >= 36% and less than 80%, then the sample size will be 
adjusted to retain the original power of 80% or doubling the sample size, whichever 
is the smallest.  
• 
If the conditional power is >= 80%, then the study will continue as is.   
The sample size may also be adjusted to reflect the Partial Repair control success percent. 
 
If the dropout rate is >10% for reasons other than safety or effectiveness, then the sample 
size will be increased accordingly to ensure that the PP accrual target is met. 
Regardless of the size of the CP, the study sample size will not be reduced. 
 
Data Provided to DSMB:  
The DSMB will receive a statistical report, the details on the content of the report is 
described in the DSMB charter.    
 Stopping Rule:    
The study will not be stopped for superiority. 
Information Provided to Sponsor by Data Safety Management Board (DSMB): 
The DSMB will make recommendations to the Sponsor on the futility and sample size 
adjustment and any safety concerns. 
Type I Error Rate Adjustment: 
 
The overall Type I error rate will be one-sided 2.5%, which is equivalent to two-sided 5%. 
There will be no Type I error rate adjustment as there is no intention to stop the study for 
efficacy benefit. In addition, the sample size is planned to be increased when the interim 
conditional power is promising and this will protect the Type 1 error (Mehta, Pocock – 
2000).  

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 43 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.9 
Effectiveness Analyses 
The primary effectiveness analysis will be conducted after all recruited subjects have reached 
their primary endpoint at the Month 12 post treatment.  This analysis will evaluate the 
primary endpoint at Month 12, plus all available imaging and key safety data; results will be 
presented according to unblinded treatment group. This initial report will be used to submit 
the primary results of the study.  
All subjects will be followed out to Month 24 to extend all analyses through Month 24 for the 
end of study analysis.   Upon study completion, the analysis for the secondary endpoints will 
be conducted and reported inclusive of all available imaging and safety data.  This subsequent 
report will be used to submit the final results of the study, including the Month 12 and Month 
24 post treatment assessments.  
4.10 General Statistical Considerations  
All collected study data will be presented in subject data listings. Statistical analyses will 
be performed using SAS® version 9.3 or later. Descriptive statistics (n, mean, standard 
deviation, median, minimum and maximum) will be calculated by treatment group for 
continuous variables. Frequencies and percentages will be presented by treatment group for 
categorical variables. 
4.11 Analysis Populations  
4.11.1 Intent-to-Treat Population 
The Intent-to-Treat population is defined as all randomized subjects who have had at least 
one post treatment efficacy assessment analyzed as treated.  
The ITT analysis population will be used as the primary analysis population supportive of 
superiority and will also be used to generate all other effectiveness endpoints in support of 
superiority and to confirm non-inferiority. 
4.11.2 Per Protocol Population 
The per-protocol analysis set (PP) includes all subjects in the ITT analysis set without any 
major protocol deviations. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 44 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Given that this is a non-inferiority analysis, the PP analysis population will be used as the 
primary analysis population supportive of non-inferiority and will also be used to generate 
all other effectiveness endpoints in support of non-inferiority and to confirm superiority.  
4.11.3 Safety Population 
The Safety population is defined as all randomized subjects who underwent the study 
surgical procedure (i.e., InSpace device or Partial Repair). This population will be used for 
the analysis of safety parameters. 
4.11.4 Covariates 
For efficacy analyses, gender will be used as a covariate in the primary endpoint analysis 
models while gender and the baseline covariate will be used as covariates in secondary 
effectiveness endpoint analyses. 
4.11.5 Missing Data 
For efficacy evaluation data points, SAS PROC MI will be used to deal with missing data; 
the method will be detailed in the Statistical Analysis Plan (SAP) for the study. 
4.11.6 Multiple Comparisons and Multiplicity 
For the primary endpoint, non-inferiority hypotheses will be tested at Month 12 for the 
primary endpoint first and then for two first-ranked secondary endpoints (WORC and 
ASES).  Type I error will be controlled by requiring significant (one-sided p≤0.025) for 
non-inferiority testing to achieve an extended claim in the following pre-defined order 
using the non-inferiority margins specified in the SAP:   
• Mean WORC change from pre-operative baseline is non-inferior at Week 6 and 
maintained at Month 12 for the InSpace device. 
• Mean ASES change from pre-operative baseline is non-inferior at Week 6 and 
maintained at Month 12 for the InSpace device. 
Superiority will also be tested if non-inferiority is proven penalty-free per claim using one-
sided p<0.025 since the alternative hypothesis of superiority is a subset of the alternative 
hypothesis of non-inferiority.  Thus, each endpoint, for which non-inferiority is 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 45 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
sequentially established, will then be tested for superiority; the inability to reach 
superiority for a specific endpoint will not terminate the sequential testing plan. 
There are no further multiple comparisons involving time or endpoints to impact the 
overall Type I error. 
4.12 Statistical Methods  
A SAP will be developed and approved before the interim analysis database is locked. The 
SAP will present the detailed statistical methodology to be used in analyzing the efficacy 
and safety data from this study.  
All the effectiveness endpoints will be analyzed using both the ITT (primary for 
superiority and secondary for non-inferiority) and PP (primary for non-inferiority and 
secondary for superiority) populations.  The PP population will be  primary to test non-
inferiority while the ITT population will be primary to test superiority.  The ITT 
population analyses will not be performed if less than 5% of the ITT population is 
excluded or did not use the randomized treatment. The ITT analysis will be performed 
using the randomized treatment assigned while the PP analyses will be performed using the 
actual treatment used.  All safety analysis will be conducted using the safety population 
according to the actual study treatment.  
All primary and secondary endpoints will be tested using one-sided 97.5% confidence 
intervals.  All primary and secondary analyses will be repeated for the ITT population. 
All data collected will be summarized according to the variable type:  
• Continuous data summaries comparing treatment groups will include:  
o Number of observations, mean, standard deviation, median, and minimum and 
maximum values.   
o Unpaired t-tests for the mean changes from baseline for each secondary 
outcome at each nominal visit.  
o Generalized Estimating Equation (GEE) analysis (SAS PROC MIXED) 
analysis including the respective baseline covariate, age, gender, treatment, 
visit, and visit-treatment interaction.  

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 46 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Categorical data summaries will include: 
o Frequency counts and percentages.  
4.12.1 Subject Disposition  
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects 
screened, randomized, completed, and discontinued during the study, as well as the reasons 
for all post-treatment discontinuations will be summarized by treatment group. Disposition 
and reason for study discontinuation will also be provided as a by-subject listing.  
4.12.2 Demographic and Baseline Characteristics  
Demographic and baseline characteristic data will be summarized descriptively and/or 
presented as a by-subject listing for the Safety population and Per Protocol populations. 
4.12.3 Protocol Deviations 
The deviations occurring during the clinical study will be summarized and/or presented as 
a by-subject listing.  
4.12.4 Prior and Concomitant Medications  
Concomitant medications will be summarized separately for the Safety and Per Protocol 
populations. All prior and concomitant medications recorded in the case report form will 
be coded to the drug substance level (i.e., generic term) using the most recent version of 
WHO Drug. Descriptive summaries, by treatment group, will be prepared using the coded 
term. All prior, continuing, and new medications recorded in the case report form will be 
listed.   
4.12.5 Primary Endpoint Analysis 
The primary analysis will be a logistic regression model for Month 12 success with age, 
gender, and treatment as the model covariates for the PP and ITT populations using the 
composite endpoint.  The method of Firth (Firth, 2013) will be used to compute unbiased 
percent estimates of the composite endpoint for each treatment group from the logistic 
regression model odds ratio estimate. 
The same approach will be used for the Month 24 analysis using the PP and ITT 
populations.   

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 47 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
4.12.6 Secondary Endpoint Analyses 
Endpoint-specific Generalized Estimating Equation (GEE) models (SAS PROC MIXED) 
will be used to further evaluate the secondary endpoints for non-inferiority and superiority 
using the PP and ITT populations. The non-inferiority margins (δ) will be prospectively 
defined in the AP. The method will be provided in detail in the SAP for the study. 
Additionally, the composite endpoint at Months 12 and 24 except requiring: (1) no 
subsequent secondary surgical interventions (SSSI) in the index shoulder, and (2) no 
Serious Adverse Device Effects (SADEs) will be performed with multiple time point 
iterations determining when WORC and ASES clinical improvements threshold are 
achieved. The method will be provided in detail in the Statistical Analysis Plan (SAP) for 
the study. 
4.12.7 Other Outcome Analyses 
The following descriptive analyses will further support publications comparing the 
InSpace device with Partial Repair control as per the original SAP. Unpaired t-tests and 
one-sided 97.5% confidence intervals will be computed at Weeks 6 and 12 as well as at 
Months 6, 12, and 24 for the PP and ITT populations: 
• Change from baseline in the mean and mean percent WORC scores 
• Change from baseline in the mean and mean percent American Shoulder and 
Elbow Surgeons (ASES)  
• Change from baseline in the mean and mean percent Constant-Murley Shoulder 
Outcome Score  
• Distribution change from baseline in the EuroQOL five dimensions questionnaire 
(EQ-5D-5L)  
• Change from baseline in the mean and mean percent Visual Analogue Scale (VAS) 
scores from baseline 
• Change from baseline in the mean and mean percent Range of Motion (ROM)  
• Composite endpoint success at Month 24 
 
4.12.8 MRI  
MRI findings will be summarized descriptively.  At Month 12 post-treatment, shoulder 
joint and surrounding tissue condition for both InSpace and Partial Repair will be 
described .  In addition, the device residual will be evaluated for the InSpace group at 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 48 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Month 12.   At Week 6, the device location in the sub-acromial space will be described for 
the InSpace group only (Group I: InSpace device [includes only subjects enrolled under 
Protocol V3.0, May 1, 2017]). 
4.12.9 Safety Analyses  
All safety assessments will be tabulated and no hypothesis testing will be conducted in this 
analysis. For continuous variables data, will be summarized by treatment group using n, 
mean, standard deviation, median, minimum and maximum values. For categorical 
variables, data will be summarized by treatment group using frequency and percentage.     
The Safety population will be used for all analyses of safety. All safety parameters will be 
presented descriptively and as data listings.   
 
4.12.9.1 Adverse Events / Adverse Device Effects 
Adverse Events will be coded using most recent version of MedDRA. Treatment Emergent 
AE’s (TEAE) are defined as events with an onset on or after the subject randomization. 
TEAEs will be summarized by treatment group, System Organ Class, and preferred term. 
The following TEAE summaries will be provided: 
▪ Overall TEAEs 
▪ TEAEs by severity grade 
▪ TEAEs by relationship to study device. 
Related AEs (ADEs) will also be presented.  In addition, separate summaries of SAEs and 
SADEs will also be presented. 
The total number of subjects with at least one AE/ADE and the number of AEs/ADEs will 
be derived.  If more than one AE/ADE with the same preferred term occurs within a 
subject during the study period, they will be counted only once for that subject using the 
worst reported severity and causal relationship to the intervention. AEs/ADEs will also be 
tabulated versus worst severity and worst relationship to the intervention.  
Symptoms recorded before administration of intervention will only be presented in listings. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 49 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
5 
SAFETY AND ADVERSE EVENTS 
5.1 Definitions 
 
5.1.1 
Adverse Event 
An AE can be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of a study device, whether or not considered related to the study 
device. 
5.1.1.1 Expected Adverse Events 
Expected Adverse Events include: 
• Post-operative fever 
• Hematoma 
• Localized pain 
• Increase in shoulder pain 
• Sensation decrease at incision site 
• Inflammation 
• Infection 
• Prolonged surgery time due to device breakage or malfunction 
 
5.1.2 
Adverse Device Effect 
ADEs are AEs caused by or related to the device. 
5.1.3 
Serious Adverse Events 
Events are classified as serious if they meet any of the following criteria (in accordance 
with the recommendations of ICH [Federal Register, October 7, 1997, Vol. 62, No. 194, pp 
52239-45]): 
• Results in death, 
• Is life-threatening (NOTE:  the term “life-threatening” in the definition of 
“serious” refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe), 
• Requires inpatient hospitalization or prolongation of existing 
hospitalization, 
• Results in persistent or significant disability/incapacity,  
• Is a congenital anomaly/birth defect 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 50 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Additionally, events are classified as serious if they meet any of the following criteria: 
• Requires intervention to prevent permanent impairment/damage, or 
• Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered a serious adverse device effect 
when, based upon appropriate medical judgment, they may jeopardize the 
subject and may require medical or surgical intervention to prevent one of 
the outcomes listed above.  
5.1.4 
Unanticipated Adverse Device Effect (United States) 
An Unanticipated Adverse Device Effect is described 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 (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 (21 CFR 812.3(s)). 
5.1.5   Reportable Incident (Canada) 
According to the Canadian Medical Devices Regulations (Sections 59 and 81), a reportable 
incident is any incident that: 
(a) is related to a failure of the device or a deterioration in its effectiveness, or any 
inadequacy in its labeling or in its the directions for use; and 
(b) has led to the death or a serious deterioration in the state of health of a patient, 
user or other person, or could do so were it to recur. 
5.2  Recording of Adverse Events and Incidents 
At each contact with the subject, the Investigator or designee must seek information on 
AEs through questioning. Information on all AEs should be recorded immediately in the 
source document and in the appropriate AE module of the CRF. All clearly related signs, 
symptoms, and abnormal diagnostic procedures results should be recorded in the source 
document, though should be grouped under one diagnosis.   
All AEs occurring during the study must be recorded in standard medical terminology. The 
clinical course of each event should be followed until resolution, stabilization, or until it 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 51 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
has been determined that the study intervention or study participation is not the cause. All 
unresolved AEs should be followed by the Investigator until the events are resolved, the 
subject is lost to follow-up, through the end of the study, or until it has been determined 
that the study intervention or participation is not the cause (whichever timing occurs first). 
Any Serious Adverse Event (SAE) that occurs until thirty (30) days after the study and is 
considered to be related to the study device or study participation should be recorded and 
reported immediately. 
5.3  Reporting  
5.3.1 
Adverse Event Reporting Period 
The study period during which AEs must be reported is defined as from the initiation of 
any study treatment or randomization through the end of the study intervention follow-up.  
5.3.2 
Reporting Adverse Events 
Any AE (clinical sign, symptom, or disease) temporally associated with the use of this 
study device, whether or not considered related to the study device, shall be documented 
on the AE CRF, except those physical assessment findings that are considered to be 
clinically insignificant.  
All AEs meeting the above noted criteria reported by the subject or observed by the 
Investigator will be individually listed. The description of the event (confirmed diagnosis, 
if available), date of onset, date of resolution, severity and relationship to study device, 
action taken, outcome, and seriousness will be reported. 
The Investigator will evaluate all AEs as follows:  
• 
CTCAE Grade (Intensity) Assessment 
The guidelines outlined in CTCAE v4.03 will be used for assessing the intensity of the 
event. The general guidelines for assessing the AE grade appear below.  Full guidelines 
may be obtained at http://evs.nci.nih.gov/ftp1/CTCAE. 
 
Table 3: CTCAE v4.03 General Guidelines 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 52 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
(ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE.‡ 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, 
etc. 
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
‡Unlike the AE outcome assessment (see Section 13.3.2), a subject may have more than one Grade 5 event. 
-Common Terminology Criteria for Adverse Events (CTCAE), v4.03: June 14, 2010 
 
 
• 
Causality Assessment 
AEs will be assigned a relationship (causality) to the study treatment or surgical 
procedure.  The Investigator will be responsible for determining the relationship 
between an AE and the study treatment/surgical procedure.  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 study treatment/surgical procedure. 
Relationship of AEs to study treatment will be classified as follows: 
o Not Related: Any reaction that does not follow a reasonable temporal 
sequence from administration of the study device AND that is likely to have 
been produced by the subject’s clinical state or other modes of therapy 
administered to the subject. 
o Related: A reaction that follows a reasonable temporal sequence from 
administration of the study device or control surgical procedure AND that 
follows a known response pattern to the suspected device/surgical 
procedure. 
• Action Taken as a Result of the Event 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 53 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
The action taken in terms of treatment provided will be as either: none, medication 
administered, therapy administered, surgery, study treatment unblinded, or other (with a 
specification). 
• Outcome Assessment 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, 
ongoing, lost to follow-up or death.  Only one AE per subject is allowed to have an 
outcome assessment as “death.”  If there are multiple causes of death for a given subject, 
only the primary cause of death will have an outcome of death. 
5.3.3 
Reporting Serious Adverse Events and Incidents 
For any SAE the Principal Investigator must notify the Sponsor’s Medical Monitor, within 
24 hours of becoming aware of the event and send the completed Serious Adverse 
Event/Unanticipated Adverse Device Effect (SAE/UADE) Report to the Sponsor’s 
Medical Monitor within 48 hours. In addition, all IRB/REB reporting requirements will be 
followed. 
The Principal Investigator shall make an accurate and adequate report of any SAEs or 
Unanticipated Adverse Device Effects (UADE). The Principal Investigator shall 
document any such report on the appropriate CRF and fax/email any initial or follow-up 
report to the Sponsor‘s Medical Monitor and to the IRB/REB (as applicable) that has 
reviewed and continues to review the study. 
• Pre-existing Condition: 
A pre-existing condition, other than the condition being treated, is one that is 
present at the start of the study. A pre-existing condition is recorded as an AE if 
the frequency, intensity, or the character of the condition worsens during the 
study. 
• General Physical Assessment Findings: 
At screening, any clinically significant abnormality should be recorded as a 
preexisting condition. At the end of the study, any new clinically significant 
findings/abnormalities that meet the definition of a SAE must be recorded and 
documented as a SAE.  
• Post-study Serious Adverse Event: 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 54 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
All unresolved SAEs should be followed by the Investigator until the events are 
resolved, the subject is lost to follow-up, through the end of the study, or until it 
has been determined that the study intervention or participation is not the cause 
(whichever timing occurs first). At the last scheduled visit, the Investigator 
should instruct each subject to report any subsequent event(s) until thirty (30) 
days after study completion that the subject or the subject’s personal physician 
believes to be related to participation in the study. The Investigator should 
notify the Sponsor’s Medical Monitor of any death or SAE occurring at any 
time after a subject has discontinued or terminated study participation that is 
related to the study.   
• Hospitalization, Prolonged Hospitalization, or Surgery: 
Any medical conditions that occurs after randomization and results in 
hospitalization or prolonged hospitalization should be documented and reported 
as a SAE unless specifically instructed otherwise in this protocol. Any 
condition responsible for surgery should be documented as a SAE if the 
condition meets the criteria for a SAE.  
Neither the condition, hospitalization, prolonged hospitalization, nor surgery 
are reported as a SAE in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective 
surgical procedures for a preexisting condition.  
• Hospitalization or prolonged hospitalization for therapy of the target 
disease of the study, unless it is a worsening or increase in frequency of 
hospital admissions as judged by the Investigator (e.g., secondary post-
operative hemorrhage). 
5.3.3.1 Investigator Reporting:  Notifying the Sponsor 
Any SAE or UADE must be reported to the Sponsor’s Medical Monitor via telephone, 
fax, or email within 24 hours of becoming aware of the event:  
 
SPONSOR’S MEDICAL MONITOR CONTACT INFORMATION 
Josh Krotec, MD 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 55 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Phone: 484-832-8770 
Email: Global.SAEinbox@chiltern.com  
Within 48 hours after the initial report, the Investigator must provide further information to 
the Sponsor’s Medical Monitor on the SAE or UADE in the form of a written narrative. 
This should include a copy of the completed SAE/UADE Report Form and any other 
related diagnostic information that will assist in the understanding of the event. Significant 
new information on ongoing SAEs should be provided promptly to the Sponsor’s Medical 
Monitor. All identifiable reference to the subject except for the subject screening number 
will be redacted from any report sent to the Sponsor’s Medical Monitor.  
5.3.3.2 Investigator Reporting: Notifying Health Canada 
Investigators are responsible for reporting device related serious adverse events and 
incidents to Health Canada within 72 hours.  The Investigator shall assist the Sponsor in 
generating a preliminary report within 10 days, containing preliminary observations, a 
course of action for the investigation, and a timeline for a final report (Section 60 of the 
Medical Device Regulations). 
5.3.3.3 Investigator Reporting: Notifying the IRB/REB 
Investigators are responsible for safety reporting to their IRB/REB. Investigators are 
responsible for complying with their IRB/REB’s reporting requirements for SAEs, though 
they must notify their IRB/REB within 10 working days of becoming aware of the event 
for any potential UADEs (21 CFR 812.150(a)(1)). The Investigator shall assist the Sponsor 
in generating the report of the UADE evaluation within 10 days after the Sponsor first 
receives notice of the effect. (21 CFR 812.46(b), 812.150(b)(1)). 
5.3.3.4 Reporting Deaths 
The following describes the Investigator reporting requirements in the event of a death, 
considered a SAE, which occurs during the course of a study: 
• Notify the Sponsor’s Medical Monitor within 24 hours of becoming 
aware of the event, 
• Provide the completed SAE/UADE Report Form to the Sponsor’s 
Medical Monitor within 48 hours of the event, 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 56 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Notify the IRB/REB of the death per IRB/REB reporting requirements. 
Should the Investigator determine the death to be device-related and unanticipated, it is 
considered an UADE, and the following Investigator reporting requirements should be 
followed: 
• Notify the Sponsor’s Medical Monitor within 24 hours of becoming 
aware of the event, 
• Provide the completed SAE/UADE Report Form to the Sponsor’s 
Medical Monitor within 48 hours of the event, 
• Notify the IRB/REB of the death per IRB/REB reporting requirements, 
but no later than 10 days of becoming aware of the event 
5.3.4 
Informed Consent Violation Reporting 
If the Investigator uses the study device without obtaining informed consent, the 
Investigator shall report such use to the Sponsor and the reviewing IRB/REB within 5 
working days after the use occurs (21 CFR 812.150(a)(5)).  
5.3.5 
Protocol Deviation Reporting 
The Investigator shall notify the Sponsor and the reviewing IRB/REB of any deviation 
from the protocol to protect the life or physical well-being of a subject in an emergency. 
Such notice shall be given as soon as possible, but in no event later than 5 working days 
after the emergency occurred (21 CFR 812.150(a)(4)).  All other deviations from the 
protocol will be reported on the appropriate CRF and reported to the IRB/REB, if required.  
Every effort shall be made to comply with the requirements of the protocol to avoid 
deviations.   
5.3.6 
Progress Reports 
The Investigator shall submit Progress Reports on the study to the Sponsor and the 
reviewing IRB/REB at regular intervals, but in no event less often than yearly (21 CFR 
812.150(a)(3)).  

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 57 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
5.3.7 
Final Report 
The Investigator shall, within 3 months after termination or completion of the study or the 
Investigator's part of the study, submit a Final Report to the Sponsor and the reviewing 
IRB/REB (21 CFR 812.150(a)(6)). 
5.4 Unblinding Procedures 
Data are to remain blinded per protocol throughout the study. However, unblinding of 
subjects by the DSMB, data manager and/or statisticians may occur in the event of a SAE 
that is deemed related to the study intervention.  If time permits, the Investigator should 
make every attempt to contact the Sponsor and/or Medical Monitor before unblinding any 
subjects’ treatment. For emergent unblinding, appropriate study personnel must contact the 
Sponsor and the Medical Monitor as soon as possible after the incident to report the details 
surrounding the emergency unblind and to receive instruction on follow-up procedures. 
5.5 Data Safety Monitoring Board 
The Data and Safety Monitoring Board (DSMB) consists of a group of individuals 
(including independent Statistician and at least one independent Senior Orthopedic 
Surgeon experienced with the study indication), appointed by the Sponsor or its designee, 
with pertinent expertise that will review accumulated data at the interim analysis from the 
study. The DSMB advises the Sponsor regarding the continuing safety of subjects and 
those yet to be voluntarily recruited to the study, as well as the continuing validity and 
scientific merit of the study. Unblinded data reviewed by the DSMB will be kept 
confidential and protected from inadvertent or inappropriate access by the Sponsor or its 
designee. Following review of data generated from the interim analysis, the DSMB may 
advise the Sponsor to continue, redesign, or stop the study. 
5.6 Study Stopping  
The Sponsor may terminate the study at any study site, at any time, for any of the 
following reasons: 
• Non-compliance to GCP or protocol 
• Failure to enroll subjects 
• Major protocol deviations 
• Inaccurate or incomplete data 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 58 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Unsafe or unethical practices 
• Safety or performance considerations 
• Recommendation made by the DSMB 
• Administrative decision 
5.7 Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at 
his/her study site. Safety monitoring will include careful assessment and appropriate 
reporting of AEs. Medical monitoring will include a regular assessment of the number and 
type of SAEs. 
5.8 Assessment of Risks and Benefits 
Any surgical procedure poses a potential risk, and the procedures undertaken as part of this 
study are no exception. There are always risks associated with any surgery or treatment 
and associated anesthesia, including death.  
These risks have been minimized by establishing strict inclusion/exclusion criteria to 
assure only appropriate surgical candidates participate in the study. A diagnostic 
arthroscopy will be used to confirm that all inclusion criteria and no exclusion criteria are 
met.  In addition, only trained surgeons with expertise in sports medicine and expertise in 
performing arthroscopic shoulder procedures will participate in this study.   
All study participants may benefit from having frequent physician visits and close 
observation.  Additionally, the results of this study may benefit both physicians treating 
subjects and subjects diagnosed with full thickness MRCTs by generating data regarding 
the safety and outcome of the procedure.  
Subjects will be advised of the potential risks and benefits associated with this study in the 
IRB/REB approved ICF. 
5.8.1 
Risks of Procedure 
Possible risks that may occur post-operatively with an arthroscopic treatment for a full 
thickness MRCT procedure are identified as follows: 
• Deltoid detachment 
• Stiffness 
• Frozen shoulder 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 59 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
• Joint effusion 
• Tendon re-tear 
• Hematoma 
• Adhesions or arthrofibrosis 
• Hemarthrosis 
• Loss of motion 
• Localized pain 
• Sensation decrease at incision site 
• Inflammation 
• Wound infection 
• Wound drainage 
• Fever 
• Synovitis 
• Treatment failure due to rehabilitation non-compliance 
• Swelling and bruising 
• Nerve injury 
• Tendon Injury 
• Delayed wound healing 
• Vascular injury 
• Conversion to mini-open or open procedure 
• DVT 
• PE 
• General risks associated with surgery and anesthesia (i.e., dizziness, 
fainting, difficulty breathing)                                                                                                    
5.8.2 
Risks of Study Device 
Anticipated study device-related risks are identified below: 
• Tissue response to the implant 
• Re-operation of the index shoulder  
• Device displacement from the sub-acromial space 
• Prolonged surgery time due to device breakage or malfunction 
5.8.3 
Benefits of Study Device 
Potential benefits of the study device include: 
• Reduction of shoulder pain 
• Improved quality of life 
• Ability to return to activities of daily life following short rehabilitation. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 60 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
6 
DATA HANDLING AND RECORD KEEPING 
6.1 
Confidentiality  
All information and data concerning subjects or their participation in this study will be 
considered confidential and handled in compliance with the ICH E6 and all applicable 
regulations including the requirements of the Federal and Provincial Data Protection 
regulations, and additionally the Personal Information Protection and Electronic 
Documents Act (PIPEDA 2000).  Those regulations require a signed subject authorization 
informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this 
study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
Only authorized personnel, the Sponsor or its designee, and applicable regulatory bodies 
will have access to these confidential files. All data used in the analysis, reporting, and 
publication of this study will be maintained without identifiable reference to the subject.  
The HIPAA (Health Insurance Portability and Accountability Act) authorization adds to 
protections already provided by the elements of ICF and may be contained within the ICF 
document or as a separate document. The HIPAA document informs the subject that they 
can withdraw authorization to use data or samples not already submitted to the Sponsor or 
its designee and that the request must be in writing. If the subject allows samples to be 
used after withdrawal from the study, this permission may be withdrawn at a later date. 
The HIPAA authorization specifies who may review confidential medical information and 
to whom test results will be submitted. It also describes that test results obtained solely for 
research will not be part of a subject’s medical record. 
In the event that a subject revokes authorization to collect or use PHI, the Investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of 
subject authorization.  For subjects that have revoked authorization to collect or use PHI, 
attempts should be made to obtain permission to collect at least vital status (i.e., that the 
subject is alive) at the end of their scheduled study period. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 61 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
6.2 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a study necessary for the reconstruction and evaluation of the study. Source 
data are contained in source documents. Examples of source documents include, but are 
not limited to:  hospital records, clinical and office charts, laboratory notes, memoranda, 
subject’s diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate 
and complete, subject files, and records kept at the pharmacy, laboratories, and medico-
technical departments involved in the study. 
The following data may be recorded directly in the CRF, which will then be considered as 
source data:  
• WORC 
• VAS 
• ASES 
• EQ-5D-5L 
• VAS 
• Imaging observations 
6.3 
Case Report Forms 
The CRF is an integral part of the study and subsequent reports. The CRF provided by the 
Sponsor must be used to capture all study data recorded in the subject’s medical record. 
The CRF must be kept current to reflect subject status during the course of the study. Only 
a subject screening number will be used to identify the subject. The Investigator must keep 
a separate log of subject names and medical record numbers (or other personal identifiers). 
After obtaining written source document information from each subject at each visit, the 
study site will enter the data into the CRF (paper or electronic). The monitor is responsible 
for performing on-site monitoring at regular intervals throughout the study to verify 
adherence to the protocol and applicable regulations on the conduct of clinical research as 
well as to ensure completeness, accuracy, and consistency of the data entered in the CRF.  
At the study site, the monitor must have access to subject medical records, study-related 
records, and written source documentation needed to verify the entries on the CRFs. Final 
monitored and/or audited CRFs will be available at all times, unless specified in writing to 
the Sponsor. These CRFs must be reviewed and verified for accuracy by the Principal 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 62 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Investigator and signed off (via electronic and/or paper signature). A copy of the final 
CRFs will remain at the Investigator’s study site at the completion of the study. 
6.4 
Data Management 
Data management and handling will be conducted according to the study specific Data 
Management Plan in accordance with applicable guidelines.  
6.5 
Records Retention 
Investigators are required to maintain all study documentation, including CRFs, ICFs, and 
adequate records for the receipt and disposition of the investigational device according to 
the regulatory requirements and/or until notified by the Sponsor that the records may be 
destroyed. If the Principal Investigator retires, relocates, or for other reasons withdraws 
from the responsibility of keeping the study records, custody must be transferred to a 
person who will accept responsibility. The Sponsor must be notified in writing of the name 
and address of the new custodian.  
7 
STUDY MONITORING, AUDITING, AND INSPECTING 
A monitor, whether an employee of the Sponsor or its designee, has the obligation to 
follow this study closely. In doing so, the monitor will visit the study sites at periodic 
intervals, in addition to maintaining necessary contact. The monitor will maintain current 
personal knowledge of the study through observation, review of study records and source 
documentation, and discussion of the conduct of the study with the Investigator and study 
staff.  Quality assurance auditors, whether an employee of the Sponsor or its designee, may 
evaluate study conduct at the study sites. These parties must have access to any and all 
study reports and source documentation, regardless of location and format. The Sponsor 
audit reports will be kept highly confidential.  
7.1 Study Monitoring 
Monitoring of study progress and conduct will be ongoing. The study will be monitored 
throughout its active phase. The first monitoring visit during the active phase of the study 
will occur shortly after the first subject has been enrolled into the study at any particular 
study site. Subsequent monitor visits will occur as the frequency of enrollment dictates. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 63 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Monitoring of study activity will be performed using several approaches (i.e., on-site, off-
site EDC).  The study data to be 100% monitored includes, but is not limited to the 
following: endpoints, SAE, randomization, consent, inclusion and exclusion criteria. The 
Investigator will allocate adequate time for such monitoring activities. The Investigator 
will also ensure that the monitor or other compliance or quality assurance reviewer is given 
access to all the above noted study-related documents and study-related facilities (e.g., 
pharmacy, operating room, etc) and has adequate space to conduct the monitoring visit. All 
data recorded during the study will be available for audit against source data and for 
compliance with GCP (21 CFR Parts 11, 50, 54, 56, 812, ICH E6) and specific protocol 
requirements. The Principal Investigator will be responsible for the following: 
• Monitoring study conduct to ensure that the rights and well-being of subjects 
are protected; 
• Monitoring accuracy, completion, and verification of source documents; and 
• Monitoring study conduct to ensure study compliance with the 
protocol/amendment(s), GCP, and applicable regulatory requirements.  
7.2 Auditing and Inspecting 
The Investigator will permit study-related monitoring, audits, and inspections by the 
IRB/REB, the Sponsor, government regulatory bodies, and institution compliance and 
quality assurance groups of all study-related documents (e.g., source documents, 
regulatory documents, data collection instruments, study data, etc.). The Investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g., pharmacy, 
operating room, etc.). 
Participation as an Investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable institution compliance and quality 
assurance offices. 
8 
ETHICAL CONSIDERATIONS 
This study will be conducted according to the protocol, the US Code of Federal 
Regulations 21 CFR Part 50, 54, 56, and 812, the ethical principles originating from the 
Declaration of Helsinki, and Good Clinical Practice (GCP) as defined in ICH E6, and the 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 64 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
ICH Guidelines. All aspects of this study will be conducted in accordance with all national, 
state, and local laws of the pertinent regulatory authorities.  
The decision of the IRB/REB concerning the conduct of the study will be made in writing 
to the Investigator and a copy of this decision will be provided to the Sponsor before 
commencement of this study. The Investigator should provide a list of IRB/REB members 
or an IRB/REB assurance number to the Sponsor.  
8.1 Protocol Amendments 
All protocol amendments must be submitted to the regulatory authorities and the 
IRB/REB, as required. A protocol amendment is generated by the Sponsor. The 
Investigator(s) is notified of the changes. The amended and/or revised protocol cannot be 
implemented until IRB/REB and/or regulatory authority approval is received, as required. 
Protocol revisions that impact on subject safety, the scope of the study, or affect the 
scientific quality of the study must be approved by the regulatory authorities and submitted 
to the IRB/REB for approval before implementation of such revisions to the conduct of the 
study.   
The Sponsor may, at any time, amend this protocol to eliminate an apparent immediate 
hazard to a subject. In this case, the appropriate regulatory authorities will be subsequently 
notified.  In the event of a protocol revision, the ICF may require revisions, which must 
also be approved by the IRB/REB. 
8.2 Informed Consent 
All subjects for this study will be provided an IRB/REB approved ICF describing this 
study and providing sufficient information for subjects to make an informed decision about 
participation in this study. This consent form will be submitted with the Clinical 
Investigational Plan (CIP) for review and approval by the regulatory authority. The 
approved ICF will be submitted to the IRB/REB for the study. The formal consent of a 
subject, using the IRB/REB approved ICF, must be obtained prior to any study 
participation. The consent form must be signed by the subject and the Investigator and/or 
designated study staff obtaining the consent. A copy of the signed and dated ICF must be 
given to the subject, and the consent process must be documented in the source 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 65 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
documentation. Before recruitment and enrollment, each prospective subject will be given 
a full explanation of the study, allowed to read the approved ICF, and be provided with 
ample time and the opportunity to ask any questions that may arise. Once all questions 
have been answered and the Investigator is assured that the subject understands the 
implications of participating in the study, the subject will be asked to give consent to 
participate in the study by signing the ICF. As part of the consent process, each subject 
must consent to direct access to his/her medical records for study-related monitoring, 
auditing, IRB/REB review, and regulatory inspection. If an amendment to the protocol 
changes the subject participant schedule or activity or increases the potential risk to the 
subject, the ICF must be revised and submitted to the IRB/REB and regulatory authority 
for review and approval. The revised ICF must be used to obtain consent from a subject 
currently enrolled in the study if he/she is affected by the amendment, as deemed necessary 
by the reviewing IRB/REB. The revised ICF must be used to obtain consent from any new 
subjects who are enrolled into the study after the date of the IRB/REB approval. 
9 
INVESTIGATOR TRAINING 
9.1 Investigator Training 
The Sponsor will select only Investigator(s) with extensive experience in performing 
arthroscopic shoulder procedures. Training on the protocol will be provided prior to the 
start of the study. The protocol and instructions on how to complete the study 
documentation will be reviewed with the Investigator(s) and their study personnel at the 
Site Initiation Visit. All Investigators will be required to attend the initial investigator 
meeting that will include training on an inanimate shoulder model. Additionally, a field 
clinical trainer (Sponsor employee or designee) will attend at minimum the initial surgical 
procedure(s), as deemed necessary, under the supervision of the Investigator. 
9.2 Training of Study Staff 
The Investigator will ensure that appropriate training relevant to the study is given to the 
medical, nursing and other staff involved and that new information of relevance to the 
performance of this study is forwarded to the staff involved. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 66 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
10 PUBLICATION PLAN 
Authorship and contents of the publication shall be discussed between each Principal 
Investigator at the study site participating in this study and the Sponsor.  The Sponsor shall 
serve as the coordinator of multi-center study disclosures and, in the event of a 
disagreement among the Investigators, the Sponsor shall determine, in its sole discretion, 
the resolution of any such dispute.  The Sponsor shall be furnished copies of any proposed 
multi-center publication or disclosure, including, without limitation, disclosures in papers 
or abstracts or at research seminars, lectures, professional meetings, or poster sessions, at 
least 90 days prior to the proposed date for submission for publication or disclosure.  
During such 90-day period, the Sponsor shall have the right to review and require 
modification of such publication to assure the accuracy of the contents thereof and to 
delete Sponsor Confidential Information therefrom.  In addition, upon the Sponsor’s 
written request during the foregoing 90-day period, the proposed submission for 
publication or disclosure shall be delayed for a period not to exceed ninety (90) days from 
the date of such request to permit the Sponsor to file patent applications or to otherwise 
seek intellectual property protection related to information contained in such publication or 
disclosure.   
It is also agreed that no presentations or publications will be authorized individually or by 
subgroups participating in the study without the consent of the Sponsor prior to publication 
of the pooled data; provided, however, that in no event shall any Institution or Investigator 
involved in this study be restricted from submitting a publication independently after the 
expiration of 365 days from the completion of the multi-center study. 
11 INSTITUTIONAL REVIEW BOARD / RESEARCH ETHICS BOARD 
Before initiation of the study, the Investigator must obtain approval of the protocol, ICF, 
CRFs, and any advertisement for subject recruitment from an IRB/REB complying with 
the provisions specified in 21 CFR Part 56 or ICH GCP, as applicable, and pertinent 
government regulations.   
A copy of written IRB/REB approvals of the protocol, ICF, CRFs, and any advertising for 
subject recruitment (if applicable) must be provided to the Sponsor or its designee prior to 
initiation of the study. The approval letter must be signed by the IRB/REB chairman or 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 67 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
designee, identify the IRB/REB name and address, identify the protocol by title and/or 
protocol number, and include the date that approval was granted. The letter must also 
contain a statement that the IRB/REB complies with the requirements in 21 CFR Part 56 
for a study conducted under ICH or GCP, as applicable. 
The Investigator is responsible for obtaining continued review of the clinical research or 
submitting periodic progress reports, in accordance with applicable regulations, at intervals 
not exceeding one year or otherwise specified by the IRB/REB. 
 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 68 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
 
12 REFERENCES  
 
Acute Pain Management:  Operative or Medical Procedures and Trauma, Clinical Practice 
Guideline No. 1. AHCPR Publication No. 92-0032; February 1992. Agency for 
Healthcare Research & Quality, Rockville, MD; pages 116-117. 
American Academy of Orthopaedic Surgeons. Appropriate use criteria for optimizing the 
management of full-thickness rotator cuff tears, September 20, 2013. 
Aurora A, McCarron J, Ianotti J, Derwin K. Commercially available extracellular matrix 
materials for rotator cuff repairs: state of the art and future trends. J Shoulder Elbow 
Surg. 2007;16(5 Suppl):S171-S178. 
Berth A, Neumann W, Aviszus F, Pap G. Massive rotator cuff tears: functional outcome after 
debridement or arthroscopic partial repair. J Orthopaedic Traumatol. 2010;11:13-20. 
Burkhart SS. Partial repair of massive rotator cuff tears: the evolution of a concept. Orthop 
Clin North Am. 1997 Jan;28(1):125-32. 
Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic 
repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone 
Joint Surg Am. 2005;87(6):1229-1240. 
Böstman O,   Pihlajamäki H. Adverse Tissue Reactions to Bioabsorbable Fixation Devices. 
Clinical Orthopaedics & Related Research. 2000 (Volume 371); 216-227 
Bunker T. Rotator Cuff Disease. Curr Orthop. 2002;16:223-33.   
Cofield RH. Rotator cuff disease of the shoulder. J Bone Joint Surg Am. 1985;67: 974-9. 
Cole BJ, ElAttrache NS, Anbari A. Arthroscopic rotator cuff repairs: an anatomic and 
biomechanical rationale for different suture-anchor repair configurations. Arthroscopy 
2007;23(6):662-669. 
Coleman SH, Fealy S, Ehteshami JR, MacGillivrayJD, Altchek DW, Warren RF et al. Chronic 
rotator cuff injury and repair model in sheep. J Bone Joint Surg Am. 2003;85:2391-
2402 
Constant CR, Murley AH. A clinical method of functional assessment of the shoulder.Clin 
Orthop Relat Res. 1987 Jan;(214):160-4. 
Cuff D, Pupello D, Virani N, Levy J, Frankle M. Reverse shoulder arthroplasty for the 
treatment of rotator cuff deficiency. J Bone Joint Surg Am. 2008;90:1244-51 
Crim J, Burks R, Manaster BJ, Hanrahan C, Hung M, Greis P. 
Temporal evolution of MRI findings after arthroscopic rotator cuff repair. AJR Am J 
Roentgenology. 2010 Dec;195(6):1361-6. 
de Witte PB, Henseler JF, Nagals J, Vliet Vlieland TP, Nelissan RG. The Western Ontario 
rotator cuff index in rotator cuff disease patients: a comprehensive reliability and 
responsiveness validation study. Am J Sports Med. 2012; 40(7):1611-9. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 69 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Ekeberg OM, Bautz-Holter E, Keller A, Tveitå EK, Juel NG, Brox JI. A questionnaire found 
disease-specific WORC index is not more responsive than SPADI and OSS in rotator 
cuff disease. Journal of Clinical Epidemiology 2010; 63(5):575-84. 
Elhassan B, Endres NK, Higgins LD, Warner JJ. Massive irreparable tendon tears of the 
rotator cuff: salvage options. Instr Course Lect. 2008;57:153-66Encalada-Diaz I, Cole 
BJ, MacGillivray JD, Ruiz-Suarez M, Kercher JS, Friel NA, Valero-Gonzalez F. 
Rotator cuff repair augmentation using a novel polycarbonate polyurethane patch: 
preliminary results at 12 months follow-up. J Shoulder Elbow Surg. 2011;20:788-94. 
Firth David. Bias reduction of maximum likelihood estimates. Biometrika, 2013; 80:27–38. 
Freehill MQ, Harms DJ, Huber SM, Atlihan D, Buss DD. Poly-L-lactic acid tack synovitis 
after arthroscopic stabilization of the shoulder. Am J Sports Med. 2003; 31(5):643-7 
Galatz L, Griggs S, Cameron BD, Iannotti JP. Prospective longitudinal analysis of 
postoperative shoulder function: a ten-year follow-up study of full-thickness rotator 
cuff tears. J Bone Joint Surg Am. 2001;83-A(7):1052-1056. 
Galatz L, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair 
integrity of completely arthroscopically repaired large and massive rotator cuff tears. J 
Bone Joint Surg Am. 2004;86(2):219-224. 
Gartsman GM. Massive, irreparable tears of the rotator cuff. Results of operative debridement 
and subacromial decompression. J Bone Joint Surg Am. 1997;79(5): 715-21. 
Gazielly D, Gleyze P, Montagnon C. Functional and anatomical results after rotator cuff 
repair. Clin Orthop Relat Res. 1994;304:43-53. 
Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone 
Joint Surg Am. 2000;82(4):505-15. 
Goldberg SS, Bell JE, Kim HJ, Bak SF, Levine WM, Bigilani LY. Hemiarthroplasty for the 
rotator cuff-deficient shoulder. J Bone Joint Surg Am. 2008; 90:554-9. 
Goutallier D, Postel JM, Bemageau J et al. Fatty muscle degeneration in cuff ruptures. Pre- 
and postoperative evaluation by CT scan. Clin Orthop Rel Res. 1994 Jul;(304):78-83.  
Gummesson C, Atroshi I, Ekdahl C. The disabilities of the arm, shoulder and hand (DASH) 
outcome questionnaire: longitudinal construct validity and measuring self-rated health 
change after surgery. BMC Musculoskeletal Disorders 2003; 4:11. 
Harryman DT 2nd, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA 3rd. Repairs 
of the rotator cuff: correlation of functional results with integrity of the cuff." J Bone 
Joint Surg Am 1991; 73(7):982-9. 
Hsu JE, Reuther KE, Sarver JJ, Lee CS, Thomas SJ, Glaser DL, Soslowsky LJ. Restoration of 
anterior-posterior rotator cuff force balance improves shoulder function in a rat model 
of chronic massive tears. J Orthop Res. 2011 Jul; 29(7):1028-33.  
Jost B, Zumstein M, Pfirrmann CW, Gerber C. Long-term outcome after structual failure of 
rotator cuff repairs. J Bone Joint Surg Am. 2006; 88(3):472-9. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 70 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Kirkley A, Griffin S, Alvarez C. The development and evaluation of a disease-specific quality 
of life measurement tool for rotator cuff disease: The Western Ontario Rotator Cuff 
Index (WORC). Clin J Sports Med. 2003;13:84-92. 
Lehman C, Cuomo F, Kummer FJ, Zuckerman JD. The incidence of full thickness rotator cuff 
tears in a large cadaveric population. Bull Hosp Jt Dis 1995; 54(1):30-1. 
Liu X, Manzano G, Kim HT, Feeley BT. A rat model of massive rotator cuff tears. J Orthop 
Res. 2011;29:588-95 
Loew M, Raiss P. A symptom-based classification for shoulders with massive rotator cuff 
defects. Int Orthop. 2010 Feb;34(1):63-9. 
Matava MJ, Purcell DB, Rudzki JR. Partial-thickness rotator cuff tears. Am J Sports Med 2005 
Sept; 33(9):1405-17. 
Matthews TJ, Hand GC, Rees JL, Athanasou NA, Carr AJ. Pathology of the torn rotator cuff 
tendon. J Bone Joint Surg Br 2006 Apr;88(4):489-495. 
Mellado JM, Calmet J, Olona M, Esteve C, Camins A, Pérez Del Palomar L, Giné J, Sauri A. 
Surgically repaired massive rotator cuff tears: MRI of tendon integrity, muscle fatty 
degeneration, and muscle fatty degeneration, and muscle atrophy correlated with 
intraoperative and clinical findings. AJR Am J Roentgenol 2005 May;184(5):1456-63. 
Mehta, CR, Pocock, SJ. Adaptive increase in sample size when interim results are promising: 
A practical guide with examples.  Statist. Med. 2000; 00:1–6. 
Michener LA, McClure PW, Sennett BJ. American Shoulder and Elbow Surgeons 
Standardized Shoulder Assessment Form, patient self-report section: Reliability, 
validity, and responsiveness. J Shoulder Elbow Surg 2002, 11(6):587-94. 
Moser M, Jablonski MV, Horodyski M, Wright TW, Functional outcome of surgically treated 
massive rotator cuff tears: a comparison of complete repair, partial repair and 
debridement. Orthopedics 2007;30:479-82. 
Mulieri P, Dunning P, Klein S, Pupello D, Frankle M. Reverse shoulder arthroplasty for the 
treatment of irreparable rotator cuff tear without glenohumeral arthritis. J Bone Joint 
Surg Br. 2010; 92:2544-56. 
Reilly P, Macleod I, Macfarlane R, Windley J, Emery RJ. Dead men and radiologists don't lie: 
a review of cadaveric and radiological studies of rotator cuff tear prevalence. Ann R 
Coll Surg Engl 2006 Mar;88(2):116-21. 
Richards RR, An K-N, Bigliani LU, Friedman RJ, Gartsman GM, Gristina AG, Iannotti JP, 
Mow VC, Sidles JA, Zuckerman JD. A standardized method for the assessment of 
shoulder function. J Shoulder Elbow Surg. 1994;3:347-52. 
Senekovic V, Poberaj B, Kovacic L, Mikek M, Adar D, Dekel A. Prospective clinical study of 
a novel biodegradable sub-acromial spacer in treatment of massive irreparable rotator 
cuff tears. Eur J Orthop Surg Traumatol. 2013 Apr;23(3):311-6. 
The EuroQoL Group. Euro-Qol-a new facility for the measurement of health-related quality of 
life. Health Policy 1990;16(3):199-208. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 71 of 137                                                                                    CIP Version 4.0 March 26, 2018  
 
 
Senekovic V, Poberaj B, Kovacic L, Mikek M,Adar E, Dekel A, Prospective clinical study of a 
novel biodegradable sub-acromial spacer in treatment of massive irreparable rotator 
cuff tears. Eur J Orthop Surg Traumatol 2013:(23):311-316 
Tonino PM, Gerber C, Itoi E, Porcellini G, Sonnabend D, Walch G. Complex shoulder 
disorders: evaluation and treatment. J Am Acad Orthop Surg 2009;17: 125-36 
Vistosky JL, Basamania C, Seebauer L, Rockwood CA, Jensen KL. Cuff tear arthropathy: 
pathogenesis, classification and algorithm for treatment. J Bone Joint Surg Am 
2004;86(Suppl 2):35-40 
Walch G, Edwards TB, Boulahia A, Nové-Josserand L, Neyton L, Szabo I. Arthroscopic 
tenotomy of the long head of the biceps in the treatment of rotator cuff tears: clinical 
and radiographic results of 307 case.  J Shoulder Elbow Surg 2005;14(3):238-46. 
Wessel J, Razmjou H, Mewa Y, Holtby R.  The factor validity of the Western Ontario Rotator 
Cuff Index. BMC Musculoskeletal Disord 2005 May 4;6:22. 
Yamaguchi K, Ditsios K, Middleton WD, Hildenbolt CF, Galatz LM, Teefey SA. The 
demographic and morphological features of rotator cuff. A comparison of 
asymptomatic and symptomatic shoulders. J Bone Joint Surg Am 2006 
Aug;88(8):1699-704. 

Ortho-Space Ltd: CLD-OR-010 
 
CONFIDENTIAL 
THIS DOCUMENT IS CONSIDERED CONFIDENTIAL AND PROPRIETARY AND 
MAY NOT BE COPIED IN ANY MANNER WITHOUT WRITTEN PERMISSION OF ORTHOSPACE LTD. 
Page 72 of 137                                                                                    CIP Version 4.0 March 26, 2018