A Prospective, Multi-center, Randomized Controlled Study to Evaluate the Safety and Efficacy of ARCR Augmented With REGENETEN™ Bioinductive Implant System in Full-thickness Tears (Large or Massive) Repair Versus ARCR Alone
Phase: NA
Conditions: Rotator Cuff Injuries
Sponsor: Smith & Nephew, Inc.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 1 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Sponsor Name and 
Address: 
Smith+Nephew Inc. 
150 Minuteman Road 
Andover, MA 01810 
USA 
 
 
Investigational Product(s): 
R
 Bioinductive Implant System 
(hereinafter referred to as REGENETEN) 
 
 
Protocol Author(s): 
Abigail Murphy, Clinical Study Manager 
Michelle Foster, Senior Biostatistician 
 
Carol Carrigan, MHA, Medical Writer, Global Scientific 
Affairs 
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec 
2021
Page: 2 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
SIGNATURES
1.1
PRINCIPAL INVESTIGATOR SIGNATURE PAGE
This page will be returned to Smith+Nephew and a copy retained at the investigational site.
-center, Randomized Controlled 
Bioinductive Implant System in Full-thickness Tears (large or massive) Repair versus ARCR 
2.0, dated 08Dec2021, and agree to abide by all provisions set forth herein.
Investigator Obligations (ISO14155:2020) and Section 21.6 Responsibilities of Clinical Trial 
Institution and Investigator (cFDA).
I agree to ensure that the confidential information contained in this document will not be used 
for any purpose other than the conduct of the described clinical investigation without the prior 
written consent of Smith+Nephew.
Name, Address,
Professional Position
Signature
Date Signed
(DD/MMM/YYYY)

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec 
2021
Page: 3 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
1.2
COORDINATING INVESTIGATOR APPROVAL 
-center, Randomized Controlled 
Bioinductive Implant System in Full-thickness Tears (large or massive) Repair versus ARCR 
2.0, dated 08Dec2021, and agree to abide by all provisions set forth therein.
Name, Address,
Professional Position
Docusign Stamp
Prof. Chris Peach
Consultant Orthopaedic Surgeon
Manchester University NHS 
Foundation Trust
Southmoor Road, Manchester
M23 9L

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec 
2021
Page: 4 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
1.3
SPONSOR APPROVAL
Job title
DocuSign Stamp
Head of Global Clinical 
Operations
Rachael Winter, Senior 
Director, Global Clinical 
Operations
Head of Global Clinical 
Strategy
Lori Fontaine,
VP, Global Clinical 
Strategy 
Head of Global 
Biostatistics
Alan Rossington, 
Director Biostatistics & 
Data Management
Medical Affairs 
Representative
Martin Ma,
Director Clinical 
Evidence Evaluation
Regulatory Affairs 
Representative
Jenna Horsley,
Sr Regulatory Manager, 
SPM and ENT

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec 
2021
Page: 5 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
SYNOPSIS
Title of Study:
A Prospective, Multi-center, Randomized Controlled Study to 
Evaluate the Safety and Efficacy of ARCR augmented with 
REGENETEN
Bioinductive Implant System in Full-thickness Tears 
(large or massive) Repair versus ARCR alone.
Study Design:
A prospective, randomized, multi-center, controlled clinical study, 3 
study arms, 24 months follow up, adaptive design with up to 300 
subjects (130 ARCR augmented with REGENETEN; 130 ARCR 
alone and up to 40 revision repair subjects).
Study Type:
Pre-market (China), Post-market, randomized controlled trial (RCT).
Study Product: 
R
s comprised of 
disposable instruments, a resorbable bovine collagen scaffold, poly-
l/d-lactide (PDLLA) tendon anchors to secure the scaffold to the 
underlying tendon, and PEEK bone anchors to secure the implant to
bone. REGENETEN is indicated for the management and protection 
of tendon injuries/rotator cuff tendon injuries (see Indications Section 
4.4.1) in which there has been no substantial loss of tendon tissue.
Comparison Group(s):
Arthroscopic rotator cuff repair (ARCR) treatment alone.
Study Purpose:
To assess the safety and efficacy of ARCR augmented with 
REGENETEN in subjects requiring full-thickness rotator cuff tear 
repair or revision repair versus ARCR alone. The study results will 
be used to support product registration in China and post market 
clinical follow-up (PMCF) primary in Europe, Australia (AUS), New 
Zealand (NZL) and reimbursement to relevant countries.
Primary Objective:
To assess the cumulative 6 months retear rate after full thickness 
ARCR augmented with REGENETEN and ARCR alone.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 6 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Secondary 
Objective(s): 
To assess safety and efficacy of full-thickness ARCR augmented 
with REGENETEN versus ARCR alone.
Other Objective(s): 
To assess safety and efficacy of full-thickness ARCR augmented 
with REGENETEN versus ARCR alone in at-risk-groups (diabetics, 
smokers, hypertensive, heavy laborer, age > 65 years);
To assess safety and efficacy of full-thickness ARCR augmented 
with REGENETEN in revision repair subject group (observational); 
To generate health economic evidence.
Sample Size: 
Up to 300 subjects will be enrolled into the study: 
 
130 ARCR augmented with REGENETEN 
 
130 ARCR alone 
 
Up to 40 revision repair subjects will be recruited into one 
additional single group (ARCR supplemented with 
REGENETEN in recurrent tears (full-thickness tears [large or 
massive]). This group will follow the same follow-up as the 
RCT group.  
The initial RCT power analysis is based on a Lan-DeMets 
Fleming) spending function with hypothesized retear incidence of 
15% for REGENETEN and 30% for ARCR with 80% power and 5% 
significance level. The sample size of 260 RCT is based on a 
primary hypothesis of 50% reduction in retear rates. Using a group 
sequential design, a formal interim analysis will be conducted once 
50% of the planned subjects reach the 6-month follow-up at which 
point a sample size re-estimation will be performed along with 
options considered to terminate early for efficacy or futility or 
increase sample size. Up to 40 revision repair subjects will be 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 7 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
enrolled into one additional group for sub-group analysis. Further 
details will be specified within the Statistical Analysis Plan (SAP). 
Number of Study Sites:
Up to 30 study sites 
Targeted Global 
Regions: 
Singapore, Hong Kong, China, United Kingdom, Germany, 
Switzerland, France, Canada, Australia, Netherlands, Japan, New 
Zealand and United States sites.
Inclusion Criteria: 
1. Subject requires Arthroscopic rotator cuff repair (ARCR);  
2.  Subjects with a diagnosis of a symptomatic primary or recurrent 
(revision repair subject group), large or massive tear (  3 cm 
AP/ML) of the supraspinatus and/or infraspinatus tendons 
amenable to repair. For screening purposes, a  2 cm AP/ML 
tear as measured on MRI will be eligible to proceed to the 
operative visit but will have to be confirmed as  3 cm on 
arthroscopy using a calibrated probe to proceed; 
3. Subject is > 40 years of age (no upper limit); 
4. Subject provides written informed consent for study participation 
using an Independent Ethical Committee (IEC) / Institutional 
Review Board (IRB) approved consent form; 
5. Subject is willing and able to participate in required follow-up 
visits and is able to complete study activities. 
Exclusion Criteria: 
1. Subjects who are unable to tolerate magnetic resonance imaging 
(MRI), due to psychiatric or medical contraindications; 
2. Subjects with Samilson-Prieto osteoarthritis > 2; 
3. Subjects with current or prior infection of the ipsilateral shoulder; 
4. Subjects with known hypersensitivity to bovine-derived materials; 
5. Subjects with known inflammatory arthropathy, history of 
inflammatory arthropathy, or chronic joint disease; 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 8 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
6. Subjects with prior shoulder surgery (not including rotator cuff 
repair [revision repair subject group only], biceps 
tenodesis/tenotomy, distal clavicle excision [DCE], subacromial 
decompression); 
7. Subjects with an irreparable or partially reparable rotator cuff 
tear;
8. Subjects with a subscapularis tear requiring repair; 
9. Subjects requiring a concomitant labral fixation procedure; 
10. Subjects requiring a concomitant os acromiale fixation 
procedure; 
11. Subjects with glenohumeral joint instability (multiple 
dislocations/subluxations); 
12. Subjects with a subacromial or intra-articular injection within 
3 months prior to surgery; 
13. Subjects with condition(s) that contraindicate or complicate 
outcomes of ARCR e.g., > Hamada 3 rotator cuff arthropathy on 
X-ray, Goutallier atrophy > Grade 3, proximal humeral fracture or 
scapular fracture, avascular necrosis of the humeral head or 
glenoid, history of immunodeficiency disorders, history of chronic 
inflammatory disorders, oral or injected steroid use in last 
4 weeks; 
14. Subjects who are pregnant or breast feeding; 
15. Subjects who are currently involved in any injury litigation or 
workers compensation claims; 
16. Subjects who are enrolled, or plan to enroll, in another clinical 
trial during this study that would affect the outcomes of this 
study; 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 9 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
17. Subjects with a history of noncompliance with medical treatment, 
physical therapy (PT)/rehabilitation, or clinical study participation; 
18. Subject who, in the opinion of the Investigator, has an emotional 
or neurological condition that would pre-empt their ability or 
willingness to participate in the study including mental illness, 
mental retardation, and drug or alcohol abuse;
19. Subjects who do not meet the indication or are contraindicated 
Instructions for Use (IFUs); 
20. Subject that meets the definition of a Vulnerable Subject per 
ISO14155:2020 Section 3.44. 
Study Duration: 
48 months (24 month enrollment period and 24 months follow-up 
period). 
Primary Endpoint: 
The cumulative 6 months retear rate after full-thickness ARCR 
augmented with REGENETEN versus ARCR alone. Failure is 
defined as Sugaya Type IV or V retear/recurrence (full-thickness 
discontinuity seen on both coronal and oblique sagittal MRI images). 
Secondary Endpoint(s):
 
The cumulative 3, 12, and 24 months retear rate after full-
thickness ARCR augmented with REGENETEN (confirmed 
on MRI) versus ARCR alone;
 
Overall performance of full-thickness ARCR augmented with 
REGENETEN versus ARCR alone at Baseline and at 3, 6, 12 
and 24 months assessed by: 
o Oxford Shoulder Score (OSS), 
o Western Ontario Rotator Cuff (WORC)/Chinese 
version WORC (C-WORC) Index, 
o Constant-Murley Score (CM), 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 10 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
o Subjective shoulder value (SSV), 
o EuroQol 5 Dimension 5 Level (EQ-5D-5L) Score, 
o Patient satisfaction Questionnaire, 
o Pain, Visual analog scale (VAS) Score (additionally at 
baseline, 2 weeks, 6 weeks, 3 months and 6 months); 
 
MRI Tendon Findings in ARCR augmented with 
REGENETEN versus ARCR alone postoperatively at 
Baseline, 3, 6, 12 and 24 months including 
o Sugaya score, 
o Goutallier grading, 
o Total tendon thickness, tendon length, 
o Size of retear (anteroposterior [AP]/mediolateral 
[ML]), 
o Shape of retear; 
 
Outcome of Return to Work Questionnaire in ARCR 
augmented with REGENETEN versus ARCR alone 
(additionally at 2 and 6 weeks);  
 
Cumulative duration of opioid use in ARCR augmented with 
REGENETEN versus ARCR alone at 2 weeks 
postoperatively; 
 
Total operative time ARCR augmented with REGENETEN 
versus ARCR alone; 
 
Sling type and mobilization time in ARCR augmented with 
REGENETEN versus ARCR alone.
Other Exploratory 
Endpoint(s): 
 
To assess safety and efficacy as summarized in secondary 
endpoints in at-risk groups (diabetics, smokers, hypertensive, 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
Bioinductive Implant 
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 11 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
heavy laborer, age > 65 years) after full-thickness ARCR 
augmented with REGENETEN versus ARCR alone; 
 
To assess safety and efficacy as summarized in secondary 
endpoints in revision repair subject group after full-thickness 
ARCR augmented with REGENETEN; 
 
To collect health economic evidence in ARCR augmented 
with REGENETEN versus ARCR alone: 
o Aggregate health care utilization costs,  
o Number of unscheduled visits, 
o Reoperation rate, 
o Surgeon recommendation for reoperation, type of 
surgery, 
o Time of operation to time of retear, 
o Level of service (LOS): In the case of reoperation: 
How many nights did the subject spend in the hospital 
as a result of surgery? 0, 1, 2, 3, 4, 5, >5. 
Safety Data 
 
All adverse events (AEs) and complications occurring from the 
time of subject enrollment until study termination or study 
completion including intra-operative adverse events and 
complications; 
 
Device Deficiencies (DD) 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled Study to Evaluate the 
Safety and Efficacy of ARCR augmented with REGENETEN
Implant System in Full-thickness Tears (large or massive) Repair versus 
ARCR alone 
Number: REGE
Version: 2.0, 08
 Dec 2021
Page: 12 of 134
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is intended for use only 
manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the contents be disclosed by any means without prior written permiss
nor shall anyone make any use of it that is contrary to the expressed or implied wishes of Smith+Nephew.  
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
STUDY SCHEDULE 
Schedule of Event 
Screening 
(Baseline) 
Day -60 to 
Day -1
Operation 
Day 0 
2 Weeks 
Follow-
up 14 ± 5 
Days
6 Weeks 
Follow-
up 42 ± 7 
Days
3 Months 
Follow-
up 91 ± 
15 Days
6 Months 
Follow-
up 182 ± 
30 Days
M
F
up
60
Informed Consent 
X1 
 
 
 
 
 
 
Inclusion/Exclusion 
X2
X2
 
 
 
 
Demographics/Medical 
History/BMI 
X
 
 
 
 
 
Operative/Discharge Data 
X 
 
 
 
 
Oxford Shoulder Score 
X
 
 
 
X
X 
WORC/C-WORC 
X
 
 
 
X
X 
Constant-Murley Score 
X
 
 
 
X
X 
Subjective Shoulder Value 
X
 
 
 
X
X 
EQ-5D-5L 
X
 
 
 
X
X 
Patient Satisfaction 
X
 
 
 
X
X 
VAS Pain Score 
X
 
X 
X 
X
X 
Return to Work Questionnaire 
X
 
X3 
X3 
X3
X3 
Opioid Use
X4
Reoperation
X
X
X
X
MRI Assessment
X2
X
X
Concomitant 
Medication/Therapy 
X
X 
X 
X 
X
X 
Safety Assessment (AEs, DDs) 
X 
X 
X 
X
X 
End of Study/Exit 
X3 
X3 
X3 
X3
X3 
1 Date of Informed consent may be the same day or another day before screening giving the subject enough time to consider participa
2 Inclusion/exclusion confirmation will be performed at the time of screening and study procedure to confirm subject meets eligibility c
be confirmed on arthroscopy using a calibrated probe. X-Ray and MRI to confirm eligibility criteria must be within 12 months of surge
3 As appropriate.  
4 Opioid use will be documented daily from day 0 to day 14. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 13 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
CONTENTS
3.1
TABLE OF CONTENTS
Signatures ....................................................................................................................................2
1.1
Principal Investigator Signature Page ....................................................................................2
1.2
Coordinating Investigator Approval........................................................................................3
1.3
Sponsor Approval..................................................................................................................4
Synopsis.......................................................................................................................................5
Study Schedule......................................................................................................................................12
Contents.....................................................................................................................................13
3.1
Table of Contents................................................................................................................13
3.2
List of Tables.......................................................................................................................15
3.3
List of Figures .....................................................................................................................15
3.4
List of Abbreviations and Definitions....................................................................................16
Introduction.................................................................................................................................20
4.1
Background.........................................................................................................................20
4.2
Literature Summary.............................................................................................................21
4.3
Study Purpose ....................................................................................................................21
4.4
Safety Considerations.........................................................................................................22
Objective(s) ................................................................................................................................26
5.1
Primary Objective................................................................................................................26
5.2
Secondary Objective(s).......................................................................................................27
5.3
Other Objective(s)...............................................................................................................27
5.4
Claims.................................................................................................................................27
Investigational Product(s)............................................................................................................28
6.1
Identification........................................................................................................................28
6.2
Product Use........................................................................................................................33
6.3
Packaging and Labeling ......................................................................................................34
6.4
Product Accountability Procedures......................................................................................35
6.5
Surgical Technique .............................................................................................................35
Subject Enrollment and Withdrawal.............................................................................................37
7.1
Subject Population ..............................................................................................................37
7.2
Inclusion Criteria .................................................................................................................37
7.3
Exclusion Criteria ................................................................................................................38

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 14 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
7.4
Screening............................................................................................................................39
7.5
Informed Consent................................................................................................................40
7.6
Enrollment...........................................................................................................................41
7.7
Lost to Follow-Up ................................................................................................................42
7.8
Withdrawal..........................................................................................................................42
Study Design ..............................................................................................................................45
8.1
Study Design.......................................................................................................................45
8.2
Allocation and Blinding........................................................................................................47
8.3
Study Endpoints..................................................................................................................48
8.4
Methods Used to Minimize Bias and Maximize Validity ........................................................50
Study Procedures .......................................................................................................................53
9.1
Visits and Examinations ......................................................................................................53
9.2
Study Methods and Measurements .....................................................................................62
9.3
Health Economics/Quality of Life.........................................................................................68
Statistical Design ........................................................................................................................70
10.1
General...............................................................................................................................70
10.2
Analysis Populations...........................................................................................................70
10.3
Baseline Data......................................................................................................................71
10.4
Efficacy Analysis .................................................................................................................71
10.5
Safety Analyses ..................................................................................................................74
10.6
Interim Analyses..................................................................................................................74
Sample Size Justification ............................................................................................................75
Adverse Events and Device Deficiencies.....................................................................................75
12.1
Definitions...........................................................................................................................75
12.2
AE Coding Dictionary ..........................................................................................................79
12.3
Reporting Procedures .........................................................................................................80
12.4
Unblinding of Investigational Product...................................................................................82
12.5
Follow-up of Subjects with Adverse Events..........................................................................82
Investigator Obligations...............................................................................................................84
Sponsor and Monitor Responsibilities..........................................................................................84
14.1
Site Qualification Visit..........................................................................................................84
14.2
Site Initiation Visit................................................................................................................85
14.3
Sponsor Audits and Regulatory Inspection ..........................................................................85
14.4
Close-out Visit.....................................................................................................................85

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 15 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Protocol Amendments.................................................................................................................85
Confidentiality of the Study..........................................................................................................85
Statements of Compliance ..........................................................................................................86
End of Study...............................................................................................................................86
Publication Policy........................................................................................................................87
19.1
Publication of Study Data ....................................................................................................87
19.2
Data Sharing.......................................................................................................................88
References.................................................................................................................................89
Appendices.................................................................................................................................93
21.1
Protocol Amendments.........................................................................................................93
Principal Investigator Obligations (ISO14155:2011)..........................................................................119
Principal Investigator Obligations (ISO14155:2020)..........................................................................119
21.2
Instructions for Use ..........................................................................................................120
21.3
Equipment and Special Instructions...................................................................................120
21.4
Health Economic Outcome Measures/ Quality of Life Measures ........................................121
21.5
Principal Investigator Obligations (ISO14155:2020)...........................................................122
21.6
Responsibilities of Clinical Trial Institution and Investigator (cFDA China Food and Drug 
Administration).................................................................................................................................131
3.2
LIST OF TABLES 
Table 9.1.1-1: Study Procedures by Visit................................................................................................ 54
3.3
LIST OF FIGURES
Figure 1 REGENETEN Bioinductive Implant and Anchors
..28
Figure 2 REGENETEN Disposable Instruments
30
Figure 8.1-1 Study Flowchart 
Main Arms
46
Figure 8.1-1 Study Flowchart 
Revision Arm
47
Figure 12.3-1 Evaluation and Reporting of Adverse Events
81
Figure 12.3-2 Evaluation and Reporting of Device Deficiencies
.82

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 16 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
3.4 
LIST OF ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
AP
Anteroposterior
ARCR
Arthroscopic rotator cuff repair 
ASADE 
Anticipated serious adverse device effect 
BMI 
Body Mass Index 
CAN 
Canada
CH 
Switzerland
Constant/CM 
Constant-Murley 
CRA 
Clinical research associate 
CRC 
Clinical research coordinator 
CTA 
Clinical trial agreement 
CV 
Curriculum Vitae 
C-WORC 
Chinese version Western Ontario Rotator Cuff
DCE 
Distal clavicle excision 
DD 
Device deficiency 
DE 
Germany
DICOM 
Digital Imaging and Communications in Medicine
EC 
Ethics committee 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
EQ-5D-5L 
EuroQol 5 Dimension 5 Level 
EU 
European Union 
FAS 
Full analysis set 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 17 of 134 
 
 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Abbreviation 
Definition 
FDA 
US Food and Drug Administration 
FR 
France 
FTT 
Full-thickness tear 
GCP 
Good Clinical Practice 
GDPR
Global Data Protection Regulation
HIPAA
Health Information Portability Accountability Act
IB 
 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements For 
Pharmaceuticals For Human Use 
ICMJE 
International Committee of Medical Journal Editors
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IP 
Investigational product 
IRB 
Independent Review Board 
ISF 
Investigator site file 
ISO 
International Organization for Standardization
ITT
Intention-to-treat
LOCF
Last observation carried forward
LOS 
Level of service 
LTFU 
Lost to follow-up 
MHRA 
Medicines and Healthcare Products Regulatory Agency 
ML 
Mediolateral 
MRCT 
Massive rotator cuff tear 
MRI  
Magnetic resonance imaging 
NDA 
Non-disclosure agreement 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 18 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Abbreviation 
Definition 
NMPA 
National Medical Products Administration 
N, n, or No. 
Number
NSAID 
Nonsteroidal anti-inflammatory drug 
NZL 
New Zealand 
OSS
Oxford Shoulder Score
PDF
Portable document format
PG 
Performance goal 
PI 
Principal Investigator 
PLDLA 
Poly-l/d-lactide 
PMCF 
Post market clinical follow-up 
PP 
Per protocol set 
PRO 
Patient-reported outcome 
PT 
Physical therapy 
PTT 
Partial-thickness tear 
Q1 
Lower quartile 
Q3 
Upper quartile 
QA
Quality assurance
QC 
Quality control 
R&D 
Research and development 
RCT 
Randomized controlled trial 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SOP 
Standard operating procedure 
SAF 
Safety analysis set 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 19 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Abbreviation 
Definition 
TENS 
Transcutaneous electrical nerve stimulation 
UK 
United Kingdom 
US 
United States 
USADE 
Unanticipated serious adverse device effect 
VAS
Visual analog scale
WORC
Western Ontario Rotator Cuff
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 20 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
INTRODUCTION
4.1
BACKGROUND
Musculoskeletal disorders are some of the most common causes of disability in the United 
States (US) with approximately 50% of the adult population having experienced a chronic 
musculoskeletal condition lasting longer than 3 months. That 
ability to work and live full lives but also puts unnecessary burden on the healthcare system [1].
The direct cost of treating shoulder pain is approximately $7 billion annually and this figure 
excludes the indirect cost burden (i.e., missed work, lost productivity) [2]. After knee-related 
disorders, shoulders are the second most common joint causing chronic pain with an estimated 
18.7 million adults affected [3]. The most common cause of shoulder pain is rotator cuff disease 
[4, 5]. In UK, rotator cuff abnormalities represent 70% of the shoulder-related general practitioner 
consultations [6]. In separate studies conducted in Sweden and Netherlands found that the 
productivity losses due to sick leave accounted for 84% and 47% respectively within 6 months of 
shoulder pain incidence [7, 8].
Rotator cuff disease are affecting millions of people globally and is prevalent in the elderly 
patient population [9, 10]. In a global systematic review and pooled analysis of 30 studies, 
Teunis et al. (2014) concluded that prevalence of rotator cuff abnormalities rose steeply with 
increasing age, from 9.7% in patients aged 
20 years to 62% in patients aged 
80 years [11]. 
Rotator cuff tears can be split into different types of tears: Partial Tear and Full-thickness tear 
[12]. Full-thickness tears which are also the focus of this study are characterized as interruption 
of tendon continuity [13] which can lead to considerable morbidity and impairment of activities of 
daily living.
There is considerable controversy among surgeons as to the best management of rotator cuff 
tears, resulting in variation in treatment pathways and guidelines [9]. However, the majority of 
full-thickness tear repairs (<74%) are performed arthroscopically [14, 15]. In terms of the type of 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 21 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
suture repair technique used, there was a trend for double-row repair to be used more frequently 
than single-row repair in full-thickness tears [16]. 
Arthroscopic rotator cuff repair has been reported to have a good clinical result but high retear 
rates [17, 18, 19]. The retear rate of surgically repaired full-thickness rotator cuff tears have 
shown to increase in association with preoperative tear size [15] and patient age [20]. In a large 
multi-center RCT in the UK, the overall healing rate of full-thickness tears was 122/217 (56%) at 
12 months. When broken down by tear size, the retear rates were 34% (20/58), 36% (27/75), 
47% (24/51), and 73% (24/33) for small, medium, large, and massive tears, respectively [21].  
Revision rates are relatively high for full-thickness tears [17, 18, 19, 21]. These results suggest 
that the existing standard of care improves patient outcomes but may be associated with 
significant postoperative retears.  
4.2 
LITERATURE SUMMARY 
Advances in treatment have occurred over the past several years in an effort to reduce retears 
and improve patients  overall postoperative outcomes [22]. Biologic scaffolds are a recent 
development in which surgeons are using to augment repairs of rotator cuff tears in patients with 
rotator cuff pathology. The REGENETEN Bioinductive Implant system is designed to support the 
 
[23, 24]. Derived from highly purified bovine Achilles tendon, it creates an environment that is 
conducive to healing [23, 24]. It is clinically proven to increase tendon thickness [23, 24] and 
delivers excellent outcomes in patient satisfaction, recovery, and pain scores [23]. The ability to 
induce new tissue formation and limit tear progression may represent a significant advancement 
in the treatment of rotator cuff tears [23]. 
4.3 
STUDY PURPOSE 
The purpose of this study is to assess the safety and efficacy of ARCR augmented with the 
REGENETEN in subjects requiring Full-thickness tear repair. The study results will be used to 
support post market clinical follow-up (PMCF) and reimbursement in relevant countries. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 22 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
4.4
SAFETY CONSIDERATIONS
Indications
The REGENETEN Bioinductive implant System has different indications depending on the 
country and shown below:
Singapore, Hong Kong, United States: The REGENETEN Bioinductive Implant System
(compromised of disposable instruments, a resorbable collagen implant, anchors to secure the 
scaffold to the underlying tendon and PEEK anchors to secure implant to the bone) is indicated 
for the management and protection of tendon injuries which there has been no substantial loss 
of tendon tissue.
China, United Kingdom, Germany, Switzerland, France, Canada, Australia, Netherlands, Japan 
New Zealand: The REGENETEN Bioinductive Implant System (compromised of disposable 
instruments, a resorbable collagen implant, anchors to secure the scaffold to the underlying 
tendon and PEEK anchors to secure implant to the bone) is indicated for the management and 
protection of rotator cuff tendon injuries which there has been no substantial loss of tendon 
tissue.
Contraindications
The Bioinductive Implant is not designed, sold, or intended for use except as described in the 
indications for use and is contraindicated in the following situation:
The Bioinductive Implant is not indicated to replace damaged tendon or to reinforce the 
strength of any tendon repair.
The Bioinductive Implant is not indicated for patients with a known history of 
hypersensitivity to bovine-derived materials.
Tendon Anchors are not designed, sold, or intended for use except as described in the 
indications for use and are contraindicated in the following situations: 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 23 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
 
Tendon Anchors are not indicated to affix soft tissue to adjoining soft tissue or to 
reinforce the strength of any tendon repair. 
 
Tendon Anchors are not indicated where there is inadequate soft tissue support or an 
irreparable tendon system.  
The Bone Anchors are not designed, sold, or intended for use except as described in the 
indications for use and are contraindicated in the following situations:  
 
Bone Anchors are not indicated to affix soft tissue to bone or to reinforce the strength of 
any tendon repair.
 
Bone Anchors are not indicated where there is inadequate quality of bone. 
The Bioinductive Implant Placement Cannula is not designed, sold, or intended for use except 
as described in the indications for use and is contraindicated in the following situation:  
 
The Bioinductive Implant Placement Cannula is not indicated for use with implants 
manufactured by any company other than Rotation Medical/Smith+Nephew. 
The Tendon Stabilizing Guide is not designed, sold, or intended for use except as described in 
the indications for use and is contraindicated in the following situation:  
 
The Tendon Stabilizing Guide is not indicated for use with delivery instruments 
manufactured by any company other than Rotation Medical/Smith+Nephew. 
The Tendon Marker is not designed, sold, or intended for use except as described in the 
indications for use.  
The Manual Placement Instruments are not designed, sold, or intended for use except as 
described in the indications for use.  
The Tendon Anchor Inserter is not indicated for use with tendon anchors manufactured by any 
company other than Rotation Medical/ Smith+Nephew. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 24 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
The Bone Anchor Inserter is not indicated for use with bone anchors manufactured by any 
company other than Rotation Medical/Smith+Nephew.
Device Application Environment
REGENETEN System is intended for use by trained medical professionals in a hospital or 
clinical environment (equivalent to an orthopaedic operating room). The components in 
REGENETEN instrument kit will be used in a sterile environment. 
All REGENETEN components (bioinductive implant, bioinductive implant delivery system, 
tendon marker, tendon stabilizing guide, manual placement instruments, bone anchors and 
tendon anchors) are provided sterile, non-pyrogenic, for single-use only, and are packaged in a 
dual sterile seal, tray-in-tray configuration as described in Instructions for Use (IFUs) and 
surgical technique documents provided by Smith+Nephew [25, 26, 27, 28, 29, 30, 31].
Potential Adverse Effects
As with any surgery, this surgery will cause risks. Potential complications of this type of surgery 
include but are not limited to anesthesia complications; incision healing problems; trauma and 
bleeding; infection; failure of the repair or retear; nerve damage; vascular damage; pain or 
stiffness that persists; tissue inflammation.
Warnings and Precautions stated in the IFU:
Bioinductive Implant:
Do no reuse or re-sterilize.
Do not use if the product package is damaged or opened.
The Bioinductive Implant should not be applied until bleeding and infection are controlled.
Application of the Bioinductive Implant does not modify the postoperative treatment. The 
surgeon must determine motion and strength requirements according to standard 
practice.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 25 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Tendon Anchors: 
 
Do not use if the temperature indicator on the product packaging is black. 
 
Do not use if the product package is damaged or opened. 
 
Do not reuse or re-sterilize. 
 
Excessive force applied during anchor deployment may result in damage to the tissue, to 
the material being fixated, to the anchor. 
 
Overlapping anchors may result in damage to the anchor. 
Bone Anchors: 
 
Do not use if the product package is damaged or opened. 
 
Do not reuse or re-sterilize. 
 
Excessive force applied during anchor deployment may result in damage to the tissue, to 
the material being fixated, to the anchor. 
 
Inserting the Bone Anchor through excessive soft tissue and failing to engage the anchor 
into bone may not provide adequate fixation. 
Bioinductive Implant Placement Cannula: 
 
Do not use if the product package is damaged or opened. 
Do not reuse or re-sterilize.
 
The cannula should be tapped lightly when inserting into bone. Do not drive the frame 
that holds the Bioinductive Implant into the bone. 
 
Do not advance cannula against resistance or damage to device may occur. 
Manual Placement Instruments: 
 
Do not use if the product package is damaged or opened. 
 
Do not reuse or re-sterilize. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 26 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Excessive force applied during Bone Anchor deployment may result in damage to the 
material being fixated or to the anchor.
Positioning the Bioinductive Implant with the Bone Anchor Inserter nubs may result in 
damage to the Bioinductive Implant.
Driving the Bone Punch with a mallet before the bone punch is engaged with the Bone 
Anchor Inserter may result in an inability to advance the Bone Anchor into the holes.
Tendon Stabilizing Guide:
Do not use if the product package is damaged or opened.
Do not reuse or re-sterilize.
The guide wire should be tapped lightly when inserting it into bone. Do not drive the shaft 
of the Tendon Stabilizing Guide into the bone.
The tip of the guide wire is sharp. Take proper care for handling and disposal of a sharp 
instrument.
Tendon Marker:
Do not use if the product package is damaged or opened.
Do not reuse or re-sterilize.
The Tendon Marker is sharp. Take proper care for handling and disposal of a sharp 
instrument.
Tendon Marker and Tendon Stabilizing Guides are not mandatory to be used. 
OBJECTIVE(S)
5.1
PRIMARY OBJECTIVE
The primary objective of this study is to assess the cumulative 6 months retear rate after full-
thickness ARCR augmented with REGENETEN versus ARCR alone.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 27 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
5.2 
SECONDARY OBJECTIVE(S) 
To assess safety and efficacy of full-thickness ARCR augmented with REGENETEN versus 
ARCR alone. 
5.3 
OTHER OBJECTIVE(S) 
To assess safety and efficacy of full-thickness ARCR augmented with REGENETEN versus 
ARCR alone in at-risk-groups (diabetics, smokers, hypertensive, heavy laborer, age > 65 years); 
To assess safety and efficacy of full-thickness ARCR augmented with REGENETEN in revision 
repair group (observational); 
To generate health economic evidence. 
5.4 
CLAIMS 
The REGENETEN Bioinductive Implant creates an environment that facilitates rotator cuff 
tendon repair [23, 24, 32, 33], s
 induce new 
tendon-like tissue growth and disrupt disease progression [23, 24, 33, 34, 35] and indicates a 
reduction in retear rates compared to standard of care [17, 24,].
.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 28 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
INVESTIGATIONAL PRODUCT(S)
6.1
IDENTIFICATION 
Investigational Product
6.1.1.1
Description
The REGENETEN Implant System is a manual arthroscopic instrument that is used to assist in 
the arthroscopic delivery and placement of the Bioinductive Implant and is comprised of 
disposable instruments, a resorbable collagen implant, and anchors to secure the scaffold to the 
underlying tendon and bone (Figure 1).
Figure 1 REGENETEN Bioinductive Implant and Anchors
Shown from the left to right, Tendon Anchor,
Bioinductive Implant and Bone Anchor
The REGENETEN Bioinductive Implant is a bioabsorbable implant that provides a layer of 
collagen over injured tendons. After hydration, the implant is an easy-to-handle, pliable, 
nonfriable, porous collagen sheet. The REGENETEN Bioinductive Implant is available in size 
large for the study. The collagen implant consists of a resorbable type I collagen matrix derived 
from bovine Achilles tendon. It is contraindicated for use in patients with a history of 
hypersensitivity to bovine-derived materials. The device is designed to completely resorb within 
6 to 12 months.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 29 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
The REGENETEN Bioinductive Implant Delivery System is provided sterile, for single-use only in 
a dual sterile seal, tray-in-tray configuration.  
The tendon anchors are made from poly (L-lactide-co-D,L-lactide) in a molar ratio of 70% L-
lactide to 30% D,L-lactide. Polylactide materials have been used in a variety of medical devices, 
such as bone anchors, bone pins, screws, plates, and spinal fusion cages. The tendon anchors 
are intended for the fixation of prosthetic material to soft tissues and designed to completely 
absorb within approximately 12 months.
The bone anchors are made from polyetheretherketone (PEEK), which is a common polymer 
used for bone anchors in orthopedic surgery. The bone anchors are intended for fixation of soft 
tissue grafts. The bone anchors are not resorbable.  
The disposable instrument system (Figure 2) includes the arthroscopic implant delivery 
instrument, tendon anchor delivery instruments, and bone anchor delivery instruments. There is 
also tendon markers and a tendon stabilizing guide that can be used if necessary but is not 
mandatory. The tendon guide wire is a useful tool for new and infrequent users. 
 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 30 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Figure 2 REGENETEN Disposable Instruments 
 
 
 
 
 
Implant delivery instrument which comes with  
 
 
 
Bone Anchor inserter   
 
 
patch pre-loaded  
 
Tendon Anchor Inserter, Cannula, Tendon Anchors with Cartridge 
The placement instruments include the Cannula Sleeve, Cannulas, Tendon Anchor Inserter, 
Bone Anchor Inserter, and Bone Punch. The Cannula Sleeve, Cannulas, and Tendon Anchor 
Inserters are used to place and deploy the Tendon Anchors. The Bone Anchor Inserter and 
Bone Punch are used to place the Bone Anchors. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 31 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
The Tendon Marker consists of a hypodermic needle that contains an internal anchor which 
advances to maintain the position of the marker. After insertion of the Tendon Marker, a slide on 
the handle is advanced to extend an anchor out of the shaft of the needle. Tendon Marker 
should only be used if available but are not mandatory. 
The Tendon Stabilizing Guide consists of a flexible guide wire that is housed within the shaft of 
the instrument. After insertion of the guide wire into bone, the shaft of the instrument is removed 
and the guide wire is used to assist in guiding the Arthroscopic Delivery System to the proper 
location. The Tendon Stabilizing Guide is optional and can be used by new and infrequent users 
but is not mandatory. 
Generation 
Part#
Implant & Instrument SKU 
US Gen 3.5 
4566 
4403 
2504-1 
4402 (1) 
4173-1 
Bioinductive Implant with Arthroscopic Delivery System, Large  
Bone Anchors with Delivery System Advanced 
Tendon Anchors (8) 
Tendon Stabilizing Guide  
Tendon Marker (2)  
International 
Gen 3.0* 
72205198
72205200
72205201
72205206
72205202
Large Arthroscopic Bioinductive Implant 
Bone Anchors (3) with Arthroscopic Delivery System 
Tendon Anchors (8) 
Tendon Stabilizing Guide (1) 
Tendon Marker (2) 
International 
Gen 3.5 
72205307
72205205
72205201
72205206
72205202
Bioinductive Implant with Arthroscopic Delivery System, Large 
Bone Anchors with Delivery System Advanced 
Tendon Anchors (8)  
Tendon Stabilizing Guide (1)
Tendon Marker (2) 
available in the IFUs and surgical 
technique documents provided by Smith+Nephew: 
  
Gen 3.5 US 
Gen 3.5 Intl 
Gen 3.0 
Part 
IFU Version 
IFU Version 
IFU Version 
Bioinductive 
Implant  
02/2020 10601445 
Rev. D 
02/2020 10601447 
Rev. B 
02/2020 10601401 
Rev. C 
Tendon Anchors
01/2019 10601404 
Rev. B
02/2020 10601391 
Rev. C
02/2020 10601391 
Rev. C
Bone Anchors
01/2019 10601405 
Rev. B
02/2020 10601392 
Rev. C
02/2020 10601392 
Rev. C

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 32 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Tendon Stabilising 
Guide
10/2018 10601407 
Rev. A
02/2020 10601394 
Rev. C
02/2020 10601393 
Rev. C
Tendon marker
10/2018 10601408 
Rev. A
02/2020 10601395 
Rev. C
02/2020 10601395 
Rev. C
Manual Placement 
Instruments 
05/2019 10601411 
Rev. B 
02/2020 10601399 
Rev. D 
02/2020 10601399 
Rev. D 
Bioinductive 
Implant Delivery 
System
02/2020 10601444 
Rev. D
02/2020 10601448 
Rev. B
02/2020 10601393 
Rev. C
The IFUs may be updated periodically, in which case, the latest version will be used as a guide. 
6.1.1.2 
Manufacturer
The REGENETEN Bioinductive Implant manufacturer is: 
Smith+Nephew Inc. 
150 Minuteman Road 
Andover, MA 01810 
USA 
6.1.1.3 
Intended Purpose 
The REGENETEN Bioinductive Implant is indicated for the management and protection of 
rotator cuff tendon injuries in which there has been no substantial loss of tendon tissue.
Tendon Anchors are indicated for fixation of prosthetic material to soft tissues in various 
minimally invasive and open rotator cuff tendon surgical procedures, such as the management 
and protection of tendon injuries in which there has been no substantial loss of tendon tissue.  
The Bone Anchor is indicated for fixation of soft tissue grafts during rotator cuff repair. 
The Bioinductive Implant Delivery Instrument is indicated for arthroscopic delivery of the 
REGENETEN Bioinductive Implant into the subacromial space.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 33 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
The Manual placement instruments are orthopedic, manual, surgical instruments used during the 
placement of Bioinductive Implant, Bone Anchors, and Tendon Anchors.
The Tendon Stabilizing Guide is indicated for assisting in the arthroscopic placement and 
location of the Bioinductive Implant in the subacromial space. The Stabilizing Guide is not 
mandatory to be used.
The Tendon Marker is indicated for assisting in the arthroscopic placement and location of the 
Bioinductive Implant in the subacromial space. The Tendon Market is not mandatory to be used.
Comparator Treatment
Arthroscopic rotator cuff repair (ARCR) alone.
Ancillary Products
Arthroscopic measuring probe to confirm the tear size for eligibility (reusable).
6.2
PRODUCT USE
Each device is packaged with Instructions for Use and provided with surgical technique to 
ensure that the device is used properly and for the intended purpose as described in the 
specifications or IFUs
(IB) (for China only)
responsibility to ensure adherence to the IFU. Investigators must go through all steps of 
procedure at least once using all provided instruments on a test case, either in Arthroscopy Wet 
Lab or similar environment or real patient before enrollment. Investigators will be trained on the 
Investigational Product beforehand.
Recommended post-operative physical therapy guidelines for ARCR augmented with 
REGENETEN:
Shoulder immobilization for 4-8 weeks, 
passive Range of Motion (PROM)

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 34 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
active Range of Motion (AROM) begin after sling is discontinued,
no lifting >1-2 kg for 12-16 weeks,
strengthening beginning after 12-16 weeks.
6.3
PACKAGING AND LABELING
Packaging and labeling will be prepared to meet regulatory requirements. Package integrity and
labelling should be verified prior to use of the product.
Labeling of Investigational Product
The REGENETEN Bioinductive Implant System is an investigational product in China. Addition 
labels will be included on the commercial packaging to specify that the product is for clinical trial 
use only in order to meet regulatory requirements for use of investigational devices.
In the United States, Singapore, Hong Kong, Europe, Canada, Australia and New Zealand, the 
REGENETEN Bioinductive Implant System is a commercial product and will be used as 
cleared/licensed. Product labeling will be the same as per standard commercial packaging.
In Japan, the REGENETEN Bioinductive Implant System is a product that will be 
cleared/registered before study enrollment. The product will only be used either through market 
approval and/or special access approval.
For China only, labels on the REGENETEN Bioinductive Implant System contain the following 
information in addition to standard commercial packaging:
Study number,
Clinical Investigation Use Only.
Any regulatory status updates that may impact labeling requirements moving forward will be 
managed via TMP-CD-18-01 Investigational Products/Ancillary Products/Supplies Protocol.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 35 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
6.4 
PRODUCT ACCOUNTABILITY PROCEDURES  
This study is a post-market study in Unites States, Singapore and Hong Kong and the products 
will only be used when cleared/registered in Australia, New Zealand, Europe and Canada. 
However, the sponsor provides the study sites with the REGENETEN System. Therefore, a site 
level accountability log will be completed for all supplied products at each study site for 
compliance. The investigational site will maintain an inventory of the Investigational Device. The 
Sponsor or its designee will provide a log(s) to facilitate Investigational Device inventory control.
The log will contain details of receipt, use, returns etc. of Investigational Devices. All 
Investigational Device accountability logs must be retained in the Investigator Site File (ISF). 
These records must be available for inspection by the Sponsor, its designees, or by regulatory 
agencies at any time. Investigational Device Management Instructions will be provided by the 
Sponsor to the site detailing all additional forms that might need completion (e.g., confirmation of 
receipt) for Investigational Device control. 
The study monitor will ensure that the procedures and records are in place for the appropriate 
reconciliation of all Investigational Devices. As part of monitoring, the study monitor will check 
that site personnel are following the proper procedures for accountability and completing all 
necessary documentation. 
6.5 
SURGICAL TECHNIQUE 
The REGENETEN System should be used according to the surgical technique and IFUs 
provided with the investigational device per Section 6.1.1.1 
Investigators participating in this study must be proficient in arthroscopic rotator cuff repairs.  
In addition, prior to implantation of the REGENETEN System, all principal surgical investigators 
involved in the REGENETEN procedure must be trained with respect to surgical technique, use 
of the device and surgical approach, so as to ensure consistency in the implementation of the 
clinical trial protocol and the use of the investigational device. Investigators must go through all 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 36 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
steps of procedure at least once, using all provided instruments on a test case, either in 
Arthroscopy Wet Lab or similar environment or real patient before enrollment. 
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 37 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
SUBJECT ENROLLMENT AND WITHDRAWAL
7.1
SUBJECT POPULATION
Up to 300 subjects will be enrolled into the study in up to 30 sites in the United States, Canada, 
United Kingdom, France, Switzerland, Germany, China, Singapore, Hong Kong, Australia and 
New Zealand, Japan and Netherlands: 
130 ARCR augmented with REGENETEN;
130 ARCR alone;
Up to 40 revision repair subjects will be recruited into one additional single group (ARCR 
supplemented with REGENETEN in recurrent tears (full-thickness tears [large or 
massive]). 
Subjects selected for this clinical trial are in need of full-thickness rotator cuff tear repair or 
revision repair (for revision repair subject group only).
7.2
INCLUSION CRITERIA
Subjects will be considered qualified for enrollment if they meet the following criteria:
1.
Subject requires Arthroscopic rotator cuff repair (ARCR).
2.
Subjects with a diagnosis of a symptomatic primary or recurrent (revision repair subject
group), large or massive tear (
3 cm AP/ML) of the supraspinatus and/or infraspinatus 
tendons amenable to repair. For screening purposes, a 
2 cm AP/ML tear as measured 
on MRI will be eligible to proceed to the operative visit but will have to be confirmed as 
3 cm on arthroscopy using a calibrated probe to proceed.
3. 
Subject is > 40 years of age (no upper limit).
4.
Subject provides written informed consent for study participation using an Independent 
Ethical Committee (IEC) / Institutional Review Board (IRB) approved consent form.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 38 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
5. 
Subject is willing and able to participate in required follow-up visits and is able to 
complete study activities. 
7.3 
EXCLUSION CRITERIA 
Any of the following criteria will disqualify a potential subject from participation in the study: 
1.
Subjects who are unable to tolerate magnetic resonance imaging (MRI), due to 
psychiatric or medical contraindications. 
2. 
Subjects with Samilson-Prieto osteoarthritis > 2. 
3. 
Subjects with current or prior infection of the ipsilateral shoulder.
4. 
Subjects with known hypersensitivity to bovine-derived materials. 
5. 
Subjects with known inflammatory arthropathy, history of inflammatory arthropathy, or 
chronic joint disease.
6. 
Subjects with prior shoulder surgery (not including rotator cuff repair [revision repair 
subject group only], biceps tenodesis/tenotomy, distal clavicle excision [DCE], 
subacromial decompression). 
7. 
Subjects with an irreparable or partially reparable rotator cuff tear. 
8. 
Subjects with a subscapularis tear requiring repair. 
9.
Subjects requiring a concomitant labral fixation procedure.
10. 
Subjects requiring a concomitant os acromiale fixation procedure. 
11. 
Subjects with glenohumeral joint instability (multiple dislocations/subluxations). 
12. 
Subjects with a subacromial or intra-articular injection within 3 months prior to surgery. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 39 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
13. 
Subjects with condition(s) that contraindicate or complicate outcome of ARCR e.g., > 
Hamada 3 rotator cuff arthropathy on X-ray, Goutallier atrophy > Grade 3, proximal 
humeral fracture or scapular fracture, avascular necrosis of the humeral head or glenoid, 
history of immunodeficiency disorders, history of chronic inflammatory disorders, oral or 
injected steroid use in last 4 weeks. 
14.
Subjects who are pregnant or breast feeding.
15. 
Subjects who are currently involved in any litigation or workers compensation claims. 
16. 
Subjects who are enrolled, or plan to enroll, in another clinical trial during this study that 
would affect the outcomes of this study. 
17. 
Subjects with a history of noncompliance with medical treatment, PT/rehabilitation, or 
clinical study participation. 
18. 
Subject who, in the opinion of the Investigator, has an emotional or neurological condition 
that would pre-empt their ability or willingness to participate in the study including mental 
illness, mental retardation, and drug or alcohol abuse. 
19. 
Subjects who do not meet the indication or are contraindicated according to specific 
 
20.  Subject that meets the definition of a Vulnerable Subject per ISO14155:2020 Section 
3.44. 
7.4 
SCREENING 
The Investigators will continuously screen subjects during recruitment, which will continue until a 
total of up to 300 subjects (130 ACRC augmented with REGENETEN, 130 ARCR alone and up 
to 40 revision repair subjects) are recruited. It remains the decision of the Sponsor to increase or 
decrease enrollment, as necessary.  
Once a subject has completed the informed consent procedure and signed the Informed Consent 
Form (IFU), the Principal Investigator (PI), or delegated study research staff, can complete the 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 40 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
screening process to determine whether they meet all inclusion and none of the exclusion criteria. 
This might be the same day or another day, giving the subject enough time to consider 
participation. 
Participating study sites are required to document all screened subjects considered for inclusion 
in this study on a Screening and Enrollment Log. If a subject is excluded from the study, the 
reasons for exclusion will be noted on the Screening and Enrollment Log.   
In the event that a subject has the need for sequential bilateral ARCR augmented with 
REGENETEN or standard arthroscopic rotator cuff repair (ARCR), both shoulders may be 
enrolled in the study after informed consent process. Post-operative physical standard of care 
therapy guidelines and restrictions as stated in section 6.2 Product Use should be maintained for 
best outcome.  
In the event that operation is delayed and outside Screening Visit Day time window, screening 
process has to be repeated to confirm eligibility. 
7.5 
INFORMED CONSENT 
Before conducting any study related procedures, informed consent shall be obtained from all 
participating subjects according to ISO14155:2020 guidelines or applicable NMPA requirements 
in China. This can be done on the same day as the screening eligibility confirmation or another 
day giving the subject enough time to consider participation. Investigators are responsible for 
obtaining and documenting the voluntary informed consent as well as obtaining the IRB/EC 
approval for the Informed Consent Form (ICF) and any other written information provided to the 
subject. 
The ICF and any other written information provided to subjects should be revised whenever 
impo
consent. All revised ICFs must have written and dated IRB/EC approval prior to use. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 41 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
The purpose and nature of the study and the potential risks and benefits known as described in 
the written ICF should be explained to the subject in their native language.  
The subject will have sufficient opportunity to consider participation in the study. The subject, will 
read, sign, and personally date the IRB/EC-approved informed consent document(s), 
indicating their consent for enrollment. Additionally, the individual who obtains consent from the 
subject will sign and date the informed consent document. The communications with the subject 
regarding informed consent process (initial and subsequent) will be documented in the medical 
record. Subjects should receive a copy of the initial signed and dated ICF (in their native 
language) and any revised ICFs during the study. 
ICFs will comply with Health Information Portability Accountability Act (HIPAA) regulations the 
EU Global Data Protection Regulation (GDPR), The Privacy Act 1988 in Australia and the New 
Zealand Privacy Act 1993 and or applicable national regulations and laws.  
7.6 
ENROLLMENT
Every subject that has signed consent, met inclusion/exclusion criteria, and received either 
ARCR augmented with REGENETEN or ARCR alone will be considered enrolled in the study.  
In the event that a subject has a sequential bilateral ARCR augmented with REGENETEN or 
ARCR alone, both shoulders treated after informed consent can be enrolled in the study. 
A subject that has been randomized into the ARCR augmented with REGENETEN arm and with 
a diagnosis of a recurrent large or massive tear will not be enrolled into the revision repair 
subject group. However subjects that were randomized into the ARCR alone arm can be 
enrolled into the revision repair subject group in case of recurrent large or massive tears.  
Subjects that provided informed consent but do not receive the study treatment for any reason 
will be considered as screen failure. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 42 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
7.7
LOST TO FOLLOW-UP
Some actively enrolled subjects may not return for follow-up exams due to a variety of reasons. 
Study personnel must make reasonable efforts to contact the subject and document the 
following contact attempts prior to declaring a subject to be lost to follow-up (LTFU): the subject 
contacts and 1 certified letter without response. Copies of all attempts to reach the subjects per 
regular mail or email and/or the attempts to contact the subject via other means should be 
documented and that documentation should be kept with the subject s source documents at site. 
A subject will be considered LTFU if he/she does not appear for the scheduled study visit for 
2 consecutive visits and does not return for a final visit, and study personnel are unable to 
contact the subject.
7.8
WITHDRAWAL
Withdrawal from Treatment
Subjects may be withdrawn from having the study device implanted at a date close to surgery or 
during surgery for the following reasons:
At the discretion of the Investigator due to:
o
A change in treatment being clinically warranted
o
An adverse event
o
Any other significant reason identified by the Investigator.
If at any point during the study, the study device needs to be revised for any reason 
intraoperative data from the reoperation will be collected according to the Reoperation Case 
Report Form (CRF).
Reoperation cases will not be enrolled into the revision repair subject group if the subjects has 
been randomized previously into the ARCR augmented with REGENETEN arm. However
subjects that have been randomized into the ARCR alone arm can be enrolled into the Revision 
Repair subject group.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 43 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Following reoperation subjects shall continue to have follow-up visits in order to monitor the 
only. Potential data following the reoperation will not be included as study 
data but presented separately as safety data.
Withdrawal from Study
The Investigator may withdraw subjects from the study for many reasons, including but not 
limited to the following:
subject noncompliance (e.g., did not follow instructions)
subject lost to follow-up
safety reasons (e.g., AEs, ADEs, SAEs)
if the Investigator or the Sponsor stops the study for any reason and decides to withdraw 
subject(s) from the study
concurrent illness
any other significant reason identified by the Investigator.
For each case, information will be obtained in the source document and the eCRF, detailing 
circumstances leading to the withdrawal. Data collected upon point of withdrawal will be included 
as study data.
Subjects who drop out or are withdrawn will not be re-entered into the study at a later date.
Subject s Withdrawal of Consent to Participate in Study
Study participation is voluntary, and subjects may withdraw at any point during the study without 
giving their reason for doing so. Where subjects withdraw consent, the Investigator should make 
a reasonable effort to ascertain the reas
reason for withdrawal will be recorded in the eCRF and source documents.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 44 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Use of Data Following Withdrawal
In cases where the subject withdraws consent, the data collected up to the point of withdrawal 
may be used, but no additional data for that subject may be collected.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 45 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
STUDY DESIGN
8.1
STUDY DESIGN
This study is a prospective, multi-center, randomized, controlled clinical study intended to 
evaluate the safety and efficacy of ARCR augmented with REGENETEN versus ARCR alone in 
the treatment of full-thickness tears of the rotator cuff (large or massive 
according to Cofield classification) including a single group of revision repair subjects. This 
clinical trial is supporting the registration of a medical device in China and will support the post 
market clinical follow up in Europe, Australia and New Zealand after market approval and 
reimbursement to relevant countries and therefore is required to follow the requirements of 
relevant regulations issued by NMPA, PMDA MHRA, EMA, TGA, Medsafe, HealthCanada or 
FDA. 
Study duration is planned to take approximately 42 months (18-month enrollment and 24-month 
follow-up). 
The subjects meeting the inclusion/exclusion criteria specified in the protocol will receive either 
ARCR augmented with REGENETEN or ARCR alone. Subjects enrolled into the revision repair 
subject group will receive ARCR augmented with REGENETEN. 
For primary hypothesis a total of up to 260 subjects (130 ARCR augmented with REGENETEN; 
130 ARCR alone) and additionally up to 40 revision repair subjects if applicable, for sub-group 
analysis are planned to be included in up to 30 study sites. Using a group sequential design, a 
formal interim analysis will be conducted once 50% of the planned 260 subjects reach the 6-
month follow-up at which point a sample size re-estimation will be performed along with options 
considered to terminate early for efficacy or futility or to increase the sample size.
The clinical follow-up evaluation will be performed preoperatively (Baseline), 2 weeks, 6 weeks, 
3, 6, 12, and 24 months after surgery, respectively.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 46 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Figure 8.1-1 Study Flowchart - Main Arms  
 
 
 
 
 
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 47 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Figure 8.1.2 
Revision Repair Arm 
8.2
ALLOCATION AND BLINDING
Treatment Allocation
Enrolled primary subjects entering the randomized controlled part of the study will be 
randomized to either ARCR augmented with REGENETEN or ARCR alone. The randomization 
will be a 1:1 blocked scheme using an external online system to conceal allocation. The online 
system will assign a Randomization ID only after the subject meets all eligibility criteria. Details 
of the blocked scheme will be presented within the SAP.
Enrolled revision repair subjects will not be randomized. All subjects will be treated with ARCR 
augmented with REGENETEN.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 48 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Blinding
This is not a blinded study.
8.3
STUDY ENDPOINTS
Primary Endpoint
The primary study endpoint is the cumulative 6 months retear rate after full-thickness ARCR 
augmented with REGENETEN versus ARCR alone. Failure is defined as Sugaya Type IV or V
retear/recurrence (full-thickness discontinuity seen on both coronal and oblique sagittal MRI 
images).
Secondary Endpoints
The secondary study endpoints are:
The cumulative 3, 12, and 24 months retear rate after full-thickness ARCR augmented 
with REGENETEN (confirmed on MRI) versus ARCR alone;
Overall performance of full-thickness ARCR augmented with REGENETEN versus 
ARCR alone at Baseline and at 3, 6, 12 and 24 months assessed by:
o
Oxford Shoulder Score (OSS),
o
Western Ontario Rotator Cuff (WORC)/Chinese version WORC (C-WORC) Index,
o
Constant-Murley Score,
o
Subjective shoulder value (SSV),
o
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Score,
o
Patient satisfaction Questionnaire,
o
Pain, Visual analog scale (VAS) Score (additionally at baseline, 2 weeks, 6 
weeks, 3 months and 6 months);
MRI Tendon Findings in ARCR augmented with REGENETEN versus ARCR alone 
postoperatively at Baseline, 3, 6, 12 and 24 months including:
o
Sugaya score,

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 49 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
o
Goutallier grading,
o
Total tendon thickness, tendon length,
o
Size of retear (anteroposterior [AP]/mediolateral [ML]),
o
Shape of retear;
Outcome of Return to Work Questionnaire in ARCR augmented with REGENETEN 
versus ARCR alone (additionally at 2 and 6 weeks); 
Cumulative duration of opioid use in ARCR augmented with REGENETEN versus ARCR 
alone at 2 weeks postoperatively;
Total operative time in ARCR augmented with REGENETEN versus ARCR alone;
Sling type and mobilization time in ARCR augmented with REGENETEN versus ARCR 
alone.
Other Endpoints
Other Study Endpoints are:
To assess safety and efficacy as summarized in secondary endpoints in at-risk groups 
(diabetics, smokers, hypertensive, heavy laborer, age > 65 years) after full-thickness 
ARCR augmented with REGENETEN versus ARCR alone;
To assess safety and efficacy as summarized in secondary endpoints in revision repair 
subjects group after full-thickness ARCR augmented with REGENETEN;
To collect health economic evidence in ARCR augmented with REGENETEN versus 
ARCR alone:
o
Aggregate health care utilization costs,
o
Number of unscheduled visits,
o
Reoperation rate,
o
Reoperation type, type of surgery,
o
Time of baseline operation to time of reoperation,
o
Level of service (LOS): In the case of reoperation: How many nights did the 
subject spend in the hospital as a result of the surgery? 0, 1, 2, 3, 4, 5, >5.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 50 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Safety Endpoints
Safety endpoints include the collection of the following events:
All adverse events (AEs) occurring from the time of subject enrollment until study 
termination or study completion including intra-operative adverse events,
Device Deficiencies.
8.4
METHODS USED TO MINIMIZE BIAS AND MAXIMIZE VALIDITY
Multi-center
The samples from multi-center are more representative than those from single center, and the 
latter may lead to deviation of study results due to its systematic errors. The required number of 
cases can be enrolled in a shorter period, and the samples are more representative and the 
results are more generalizable.
In this study, subjects will be enrolled at multiple sites, utilizing up to 30 sites globally. This will 
reduce the effect of observer bias that might arise at any one investigational site as well as 
maximize the diversity of subjects treated.
Randomization
Subjects meeting all inclusion/exclusion criteria will be randomly allocated into any of two study 
groups in a 1:1 allocation ratio. Blocked randomization will be used to balance this allocation 
ratio by investigational site and overall. Randomization will be conducted through an online 
system. Randomization will occur and a treatment will be assigned only when subject has signed 
the ICF and satisfied all study eligibility criteria.
Measurement Consistency
For the primary endpoint (cumulative 6 months retear rate on MRI) of each site, consistency 
measurement should be performed. Failure is defined as Sugaya Type IV or V retear/recurrence

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 51 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
(full-thickness discontinuity seen on both coronal and oblique sagittal MRI images).There is a 
preference for 3.0Tesla MRI imaging, wherever available. 1.5Tesla systems will only be 
approved if 3.0Tesla MRI is not available. Images will be obtained as described in the image 
acquisition protocol (IAP).
Imaging Evaluation
For further details of imaging evaluation, refer to Image Review Guidelines. Imaging observation 
indicator is a reasonable and necessary indicator to evaluate the success rate of retear rates, 
MRI grading, and tendon thickness. To reflect the importance of imaging change over time, 
measurements should be made before surgery as well as 3, 6, 12, and 24 months after surgery.
Screening of Subjects
In order to eliminate selection bias, the Investigators will continuously screen all subjects. 
Subject recruitment continues until the completion of recruitment of 260 RCT subjects and up to 
40 revision repair subjects. 
Investigator Training
Prior to the clinical trial, the clinical research associate (CRA), coordinating with the persons in 
charge of the study sites, will train the Investigators on the study protocol, making sure they are 
familiar with the use of investigational medical device, and implement subject enrollment strictly 
in accordance with the inclusion criteria and exclusion criteria, conduct relevant examinations 
according to the protocol requirements, also master all new device-related information found 
during the clinical trial, thus to minimize the interferential factors.
Clinical Trial Monitoring
Detailed monitoring requirements will be documented in the Clinical Monitoring Plan for this 
study. The monitor is selected and appointed by the Sponsor to conduct a regular on-site 
monitoring visit, making sure that all contents in the study protocol are strictly followed. The 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2, 08 Dec 2021 
Page: 52 of 134 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
source documents are inspected to ensure consistent contents with the eCRF. Monitoring visits 
will be conducted at the start, during and at the closure of the clinical study in accordance with 
Smith+Nephew standard operating procedures (SOPs) and the Clinical Monitoring Plan. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2, 08 Dec 2021
Page: 53 of 134
CONFIDENTIAL AND PROPRIETARY
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
STUDY PROCEDURES
9.1
VISITS AND EXAMINATIONS 
Summary
For a summary of the required procedures by visit, refer to the Study Schematic Table 9.1.1-1: 
Study Procedures by Visit.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled Study to Evaluate the 
Safety and Efficacy of ARCR augmented with REGENETEN
Implant System in Full-thickness Tears (large or massive) Repair versus 
ARCR alone 
Number: REGE
Version: 2.0, 08
Dec 2021
Page: 54 of 134
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is intended for use only 
manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the contents be disclosed by any means without prior written permiss
nor shall anyone make any use of it that is contrary to the expressed or implied wishes of Smith+Nephew.  
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Table 9.1.1-1: Study Procedures by Visit
Schedule of Event
Screening 
(Baseline) 
Day -60 to 
Day -1 
Operation 
Day 0 
2 Weeks 
Follow-
up 14 ± 5 
Days 
6 Weeks 
Follow-
up 42 ± 7 
Days 
3 Months 
Follow-
up 91 ± 
15 Days
6 Months 
Follow-
up 182 ± 
30 Days 
M
F
up
60
Informed Consent 
X1 
 
 
 
 
 
 
Inclusion/Exclusion 
X2
X2
 
 
 
 
Demographics/Medical 
History/BMI 
X
 
 
 
 
 
Operative/Discharge Data 
X 
 
 
 
 
Oxford Shoulder Score 
X
 
 
 
X
X 
WORC/C-WORC 
X
 
 
 
X
X 
Constant-Murley Score 
X
 
 
 
X
X 
Subjective Shoulder Value 
X
 
 
 
X
X 
EQ-5D-5L 
X
 
 
 
X
X 
Patient Satisfaction 
X
 
 
 
X
X 
VAS Pain Score 
X
 
X 
X 
X
X 
Return to Work Questionnaire 
X
 
X3 
X3 
X3
X3 
Opioid Use 
 
X4 
 
 
 
Reoperation
X
X
X
X
MRI Assessment
X2
X
X
Concomitant 
Medication/Therapy 
X
X
X
X
X
X
Safety Assessment (AEs, DDs) 
X 
X 
X 
X
X 
End of Study/Exit 
X3 
X3 
X3 
X3
X3 
1 Date of Informed consent may be the same day or another day before screening giving the subject enough time to consider participa
2 Inclusion/exclusion confirmation will be performed at the time of screening and study procedure to confirm subject meets eligibility c
be confirmed on arthroscopy using a calibrated probe. X-Ray and MRI to confirm eligibility criteria must be within 12 months of surge
3 As appropriate.  
4 Opioid use will be documented daily from day 0 to day 14. 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 55 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Screening (Baseline) Visit 1 (Day - 60 to Day -1)
1.
Obtain written informed consent from the subject as detailed in Section 7.5. This might be 
the same day or another day before screening giving the subject enough time to consider 
participation.
----- Do not proceed until consent has been obtained -----
2.
Assign the subject a study ID in electronic data capture system.
3.
Screen the subject for protocol inclusion/exclusion criteria and surgery indication. Any 
subject who signs an informed consent but fails to meet the eligibility criteria is 
considered to be a Screen Failure.
4.
Obtain Demographic information, BMI and medical/surgical history, including information 
on all concomitant medications/therapies that is considered relevant.
5.
Obtain MRI and X-Ray (must be within 12 months of surgery) and confirm eligibility 
criteria. The tear size measurement may be provided by the radiography report or as 
determined by the Investigator.
6. 
Complete the Constant-Murley Questionnaire (Physician/Examiner completed portion).
7
Have the subject complete the OSS Questionnaire.
8.
Have the subject complete the WORC/C-WORC Questionnaire.
9.
Have the subject complete the subjective part of Constant-Murley Questionnaire.
10.
Have the subject complete the SSV Questionnaire.
11. 
Have the subject complete the EQ-5D-5L Questionnaire.
12. 
Have the subject complete Patient satisfaction Questionnaire.
13.
Have the subject complete Work Status for Return to Work Questionnaire.
14.
Have the subject complete VAS pain questionnaire.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 56 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
15.
Instruct the subject to return for the Operation Visit on the scheduled date.
Operation 
Visit 2 (Day 0)
1. 
Query subject regarding any changes in general health and the use of concomitant 
medications (e.g. oral or injected steroid use in last 4 weeks).
2.
Confirm eligibility based on arthroscopic visualization of the tear and confirm size using 
a calibrated probe.
3.
Assign the Randomization ID per randomization schedule. Screen Failure subjects 
should not be assigned randomization numbers, but their demographic information must 
be captured in the appropriate CRF with the reason for screen failure specified.
4.
Commence operation as per the randomization schedule.
5.
Collect operative and discharge data (including implant information) according to the 
CRF.
6.
If any AEs, ADEs or DD are observed or reported, they must be recorded as instructed 
in Section 12 
Adverse Events and Device Deficiencies.
7.
Instruct the subject on proper postoperative care/procedures as per standard of care 
Product Use.
8. 
Instruct the subject to document Opioid Use over the next 2 weeks on a daily basis.
9.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 3 in 14 (± 5) days.
Postoperative Follow-up Visit 3 (2 Weeks [14 days ± 5 days])
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Have the subject complete VAS pain score.
3.
Have the subject complete the Return to Work Questionnaire (if appropriate).

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 57 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
4.
Collect daily Opioid Use documentation from subject and enter into eCRF.
5.
If any Reoperation occurred complete reoperation CRF.
6.
Complete End of Study/exit information (if appropriate).
7.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 4 at 42 (± 7) days.
Postoperative Follow-up Visit 4 (6 Weeks [42 days ± 7 days])
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Have the subject complete VAS pain score.
3.
Have the subject complete the Return to Work Questionnaire (if appropriate).
4.
If any Reoperation occurred complete reoperation CRF.
5.
Complete End of Study/exit information (if appropriate).
6.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 5 at 3 months (91 ± 15 days).
Postoperative Follow-up Visit 5 (3 Months [91 ± 15 days)
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Have the subject complete VAS pain score.
3.
Complete the Constant-Murley Questionnaire (Physician/Examiner completed portion).
4.
Have the subject complete the OSS Questionnaire.
5.
Have the subject complete the WOR/C-WORC Questionnaire.
6.
Have the subject complete the subjective part of Constant-Murley Questionnaire.
7.
Have the subject complete the SSV Questionnaire.
8.
Have the subject complete the EQ-5D-5L Questionnaire.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 58 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
9.
Have the subject complete Patient satisfaction Questionnaire.
10.
Have the subject complete the Return to Work Questionnaire (if appropriate).
11.
Complete MRI assessment.
12.
If any Reoperation occurred complete reoperation CRF.
13.
Complete End of Study/exit information (if appropriate).
14.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 6 at 6 months (182 ± 30 days).
Postoperative Follow-Up Visit 6 (6 Months [182 ± 30 days])
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Have the subject complete VAS pain score.
3.
Complete the Constant-Murley Questionnaire (Physician/Examiner completed portion).
4.
Have the subject complete the OSS Questionnaire.
5.
Have the subject complete the WOR/C-WORC Questionnaire.
6.
Have the subject complete the subjective part of Constant-Murley Questionnaire.
7.
Have the subject complete the SSV Questionnaire.
8.
Have the subject complete the EQ-5D-5L Questionnaire.
9.
Have the subject complete Patient satisfaction Questionnaire.
10.
Have the subject complete the Return to Work Questionnaire (if appropriate).
11.
Complete MRI assessment.
12.
If any Reoperation occurred complete reoperation CRF.
13.
Complete End of Study/exit information (if appropriate)
14.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 7 at 12 months (365 ± 60 days).

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 59 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Postoperative Follow-Up Visit 7 (12 Months [365 ± 60 days])
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Complete the Constant-Murley Questionnaire (Physician/Examiner completed portion).
3.
Have the subject complete the OSS Questionnaire.
4.
Have the subject complete the WOR/C-WORC Questionnaire.
5.
Have the subject complete the subjective part of Constant-Murley Questionnaire.
6.
Have the subject complete the SSV Questionnaire.
7.
Have the subject complete the EQ-5D-5L Questionnaire.
8.
Have the subject complete Patient satisfaction Questionnaire.
9.
Have the subject complete the Return to Work Questionnaire (if appropriate).
10.
Complete MRI assessment.
11.
If any Reoperation occurred complete reoperation CRF.
12.
Complete End of Study/exit information (if appropriate).
13.
Instruct the subject on follow-up procedures, including returning the treatment facility for 
follow-up at Visit 8 at 24 months (730 ± 60 days).
Postoperative Follow-Up Visit 8 (24 Months [730 ± 60 days])
1.
Query subject regarding any changes in general health and the use of concomitant 
medications. If any AEs, ADEs or DDs are observed or reported, they must be recorded 
as instructed in Section 12 
Adverse Events and Device Deficiencies.
2.
Complete the Constant-Murley Questionnaire (Physician/Examiner completed portion).
3.
Have the subject complete the OSS Questionnaire.
4.
Have the subject complete the WOR/C-WORC Questionnaire.
5.
Have the subject complete the subjective part of Constant-Murley Questionnaire.
6.
Have the subject complete the SSV Questionnaire.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 60 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
7.
Have the subject complete the EQ-5D-5L Questionnaire.
8.
Have the subject complete Patient satisfaction Questionnaire.
9.
Have the subject complete the Return to Work Questionnaire (if appropriate).
10.
Complete MRI assessment.
11.
If any Reoperation occurred complete reoperation CRF.
12.
Complete Exit Visit CRF and inform subject of End of Study.
Unscheduled Visits 
Unscheduled examinations related to the study shoulder may be conducted at the discretion of 
the Investigator with all obtained information recorded in the source documents. The reason for 
the unscheduled visit as well as surgical status should be transcribed to the appropriate eCRF. If 
any adverse events or device deficiencies are observed or reported, they must be recorded as 
instructed in Section 12. - Adverse Events and Device Deficiencies. The subject should be 
scheduled to return for the next scheduled study visit within the acceptable time window.
Concomitant Medications and Therapies
Concomitant medications and concomitant therapies (e.g. use of opioids, non-opioid prescription 
medication, steroid injections to treat the index shoulder) are recorded at any time from 
enrollment into the study through the 
last study visit. 
9.1.11.1
Concomitant Medications
9.1.11.1.1Excluded Concomitant Medications
No restrictions on concomitant medications.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 61 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
9.1.11.1.2 Recording Concomitant Medication in the eCRF
Only medication related to the study treatment and therapies used to treat an adverse event
related to study device and/or study procedure and device deficiency will be recorded in the
eCRF according to the eCRF Completion Guidelines.
9.1.11.2
Concomitant Therapies
9.1.11.2.1Therapies Prohibited During the Study 
No restriction on concomitant therapies.
9.1.11.2.2Recording Concomitant Therapies in the eCRF
Only therapies related to the study treatment and therapies used to treat an adverse event 
related to study device will be recorded in the eCRF according to the eCRF Completion 
Guidelines. 
Discontinued Subjects
Discontinued subjects are those who voluntarily discontinue participation, who are withdrawn for 
reasons of safety, who are LTFU, or meet any of the criteria listed in Section 7.8 of this protocol. 
Where possible, a full Exit Visit should be completed for all subjects who discontinue the study 
early. Where consent is withdrawn, the date and any reason given for discontinuation should be 
captured, at a minimum.
Finally, if appropriate, the Investigator will also advise the subject of subsequent therapy and/or 
procedures necessary for their medical condition.
Subject Pregnancy
Pregnant or breast-feeding females are excluded from the study. If during the course of the 
study a subject becomes pregnant, study procedures that are contraindicated during pregnancy 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 62 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
and/or lactation (e.g. X-Rays, MRI) will not be obtained; however, the subject will continue to be 
followed for study visits and information will be collected regarding the outcome of the birth.
9.2
STUDY METHODS AND MEASUREMENTS
Cofield classification
The Cofield classification system will be used for all MRI analyses to assess the size of FTTs
[38]:
Small = < 1 cm
Medium = 1-3 cm
Large = 3-5 cm
Massive = > 5 cm
OSS Questionnaire
The Oxford Shoulder Score (OSS) is a questionnaire for the assessment of outcomes of 
shoulder surgery, which can reduce the observer's errors in the evaluation. It contains 12-item 
patient-reported outcome (PRO) measures specifically designed and developed for assessing 
outcomes of shoulder surgery such as assessi
degenerative conditions (e.g., arthritis and rotator cuff problems). Because of its reliability and 
effectiveness, this scoring tool is widely used in clinical practice and studies related to shoulder 
surgery outcomes [39].
The OSS consists of 12 questions each scored 0 to 4 (0=unbearable, 1=severe, 2=moderate, 
3=mild, 4=none) with 4 representing the best outcome. When the 12 items are summed, this 
produces overall scores that run from 0 to 48, with zero (0) representing a severe shoulder 
problem and 48 representing no related problem. Higher scores represent better clinical 
outcomes [39]

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 63 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
WORC/C-WORC Index
The WORC/C-WORC Index is a 21-item questionnaire assessing quality of life, evaluating the 
change in symptoms and functional ability, specific to rotator cuff tendinopathy; it is often used to 
compare pre- and postoperative changes in patients with a clinical diagnosis of an impingement 
syndrome, rotator cuff tendinopathy as well as ARCRs [40].
The WORC/C-WORC Index is self-administered, and includes a 5 different domains (physical 
symptoms, sports and recreation, work, social function, and emotions). Each question uses a 
visual analog scale (VAS) representing a 100-point scale ranging from 0 to 100. The maximum 
score is 2100 (worst possible symptoms). Zero (0) represents no symptoms at all. The final 
score can also be presented as a percentage by subtracting the total from 2100, dividing by 
2100, and multiplying by 100. This will give you an overall percentage. The total final WORC/C-
WORC Index scores can, therefore, range from 0% (lowest functional status level) to 100% 
(highest functional status level) [40].
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
Constant-Murley Score
The Constant-Murley Score is a validated assessment of pain and shoulder functionality. The 
test is divided into four subscales: pain, activities of daily living, strength and range of motion 
(forward elevation, external rotation, abduction and internal rotation of the shoulder. The 
subjective findings (severity of pain, activities of daily living and working in different positions) 
comprise 35 points and the objective (examiner assessed) measurements (arm range of motion 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 64 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
without pain, measurements of exo- and endorotation via reference points and measuring 
muscle strength) comprise the remaining 65 points, for a total of 100 points [41]. 
The Constant Score is divided into 4 subscales: pain (15 points; VAS score range of 0-15), 
activities of daily living (20 points; range 0=worst, 5=best), strength (25 points; 1 point given per 
0.5 kg of weights raised), and range of motion 
forward flexion, external rotation, abduction and 
internal rotation of the shoulder (40 points; range 0=worst, 10=best). The higher the score, the 
higher the quality of function [41].
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
Subjective Shoulder Value (SSV) (also known as Single Assessment 
Numeric Evaluation [SANE])
Note: The 
How would you rate your shoulder today as a 
The SSV is defined as a patient's subjective shoulder assessment expressed as a percentage of 
an entirely normal shoulder, which would score 100% [42].
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
Patient Satisfaction Questionnaire
The Patient Satisfaction Questionnaire is a simple subjective assessment of the success of 
not been formally validated [42].
Pre-Op: 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 65 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
The Patient satisfaction pre-Op will be documented on a visual analogue score of 0-
satisfied
fied, 100 
the most satisfied [43].
Post-Op:
This includes the VAS Patient Satisfaction Score as for pre-Op and additional five questions ask 
of the patient:
1. How well did the surgery relieve the pain?
2. How well did the surgery increase your ability to perform regular activities?
3. How well did the surgery allow you to perform heavy work or sport activities (if allowed by 
Dr)?
4. How well did the surgery meet your expectations?
Questions rated by the patient with excellent, very good, good, fair and poor.
5. Would you have the operation again if needed on another joint?
Question rated by the patient with Definitely yes, Probably yes, Possibly not, Definitely not [42].
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
VAS Pain Score
Pain is assessed on a 100-point scale ranging from 0 to 100, with zero (0) representing no pain 
and 100 representing the worst pain imaginable [42].
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 66 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Sugaya Score
The Sugaya score will be used to determine postoperative cuff integrity through magnetic 
resonance imaging classified into 5 categories: Type I to Type V. Type I indicates sufficient 
thickness with homogenously low intensity. Type II indicates sufficient thickness with partial high 
intensity. Type III indicates insufficient thickness without discontinuity. Type IV indicates
presence of a minor discontinuity, suggesting a small full-thickness tear. Type V indicates the 
presence of a major discontinuity, suggesting a medium or large full-thickness tear [43]
Goutallier Classification
The Goutallier classification will be used to classify the fatty infiltration of the rotator cuff. The 
Goutallier classification ranges from a grade of 0 indicating a completely normal muscles without 
any fatty streaks to a grade of 4 which indicates that more fat than muscle is present [44].
Grade 0: Completely normal muscle, without any fatty streaks,
Grade 1: Some fatty streaks,
Grade 2: Increased fatty infiltration, but more muscle than fat,
Grade 3: Equal amounts of fat and muscle,
Grade 4: more fat than muscle.
Return to Work Questionnaire
Generic questionnaire, covering work related questions, including demographics on 
laborer/sedentary [42].
1.
Were you working before surgery? Y/N
a. If yes, what was your job type and the nature of your work?
2.
Have you returned to work? Y/N

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 67 of 134
CONFIDENTIAL AND PROPRIETARY
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
a. If yes, how long after your operation did you return to work 
b.
to work was there a particular reason?
3.
Have you been able to return to the job you did before your surgery (doing the same 
activities)? Y/N
a. If No, is there a particular reason you c
t return to the same activities?
4.
If RTW, did you feel ready to go back to work physically? Y/N
5.
Since returning to work, did you have to take further time off due to shoulder pain or 
weakness? Y/N
a. If so, how long?
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
Duration of Opioid Use
Self-reported opioid use diary completed by the patient on a daily basis, from day 0-14, 
documenting opioid use. Consumption daily (YES/NO) x14 days
medication 
A paper questionnaire will be provided by the Sponsor to be completed by the subject. 
Responses will be recorded in the eCRF.
Imaging Examinations
Upper extremity MRIs for study participants will be collected at Baseline, at 3, 6, 12 and 24 
months. The Baseline (pre-operative) MRI follows standard of care imaging and will not follow 
the study MRI Image Acquisition Protocol. The Baseline MRI must occur within 12 months of 
enrollment into this study. MRI at 3, 6, 12 and 24 months post-surgery will be collected per 
Image Acquisition Protocol. All diagnostic images collected by the site will be modified in order to 
and provided to an external reviewer as detailed in the Image Transfer

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 68 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Protocol. The independent reviewer will be a certified radiologist selected by the Sponsor based 
on experience in orthopaedic imaging. The following reviewer assessments will be performed for 
all MRIs collected post-OP throughout the study (for endpoint analysis):
Sugaya score
Goutallier grading
Total tendon thickness, tendon length
Size of retear (anteroposterior [AP]/mediolateral [ML])
Shape of retear
All MRI assessments are detailed in the Image Review Charter. All imaging data will be stored in 
electronic Digital Imaging and Communications in Medicine (DICOM) format at the site until they 
are no longer needed in case further evaluation by an independent centralized reviewer is 
requested by NMPA, PMDA, MHRA, EMA, TGA, Medsafe, HealthCanada, or FDA.
The specific imaging evaluation requirements will be provided in a separate document to 
radiologists.
9.3
HEALTH ECONOMICS/QUALITY OF LIFE
Health economic evidence will be collected throughout the study.
EQ-5D-5L Questionnaire
The EQ-5D-5L questionnaire will be collected at the pre-operative visit and at 3-, 6-, 12- and 24-
months after surgery. A paper questionnaire will be provided by the Sponsor to be completed by 
the subject. 
The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual 
analogue scale (EQ VAS).

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 69 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each 
dimension has 5 levels to choose the most appropriate answer: no problems, slight problems, 
moderate problems, severe problems and extreme problems. The subject is asked to indicate 
his/her health state by marking the most appropriate statement in each of the five areas [45]. 
-rated health on a vertical visual analogue scale. The 
health you 
the individual respondents.
Responses for the EQ-5D-5L Score will be recorded in the eCRF.
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 70 of 134
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
STATISTICAL DESIGN
A statistical analysis plan (SAP) will be written and finalized prior to database lock. The following 
is a brief description of the analyses to be described in this plan. 
10.1
GENERAL
this study. Unless otherwise stated, all significance tests will be two-sided, performed at the 5% 
significance level. Resulting p-values will be quoted. Point estimates and their corresponding 
95% two-sided confidence intervals will be generated where appropriate. Where data summaries 
are specified, categorical or ordinal variables will be summarized with frequencies and 
percentages. Continuous variables will be summarized with the following summary statistics: 
number of observations, mean, median, standard deviation, minimum and maximum values. All 
analyses will be performed in SAS 9.4 (or later).
10.2
ANALYSIS POPULATIONS
The following study populations and analysis sets will be defined.
Full analysis set (FAS): following the Intention to Treat principle including all randomized 
patients who were recruited into the study and attended at least one post-surgery 
assessment. This analysis population includes all randomized patients in the groups to 
which they were randomly assigned, regardless of their adherence with the entry criteria, 
regardless of the treatment they actually received, and regardless of subsequent 
withdrawal from treatment or deviation from the protocol.
Per protocol set (PP): including all patients in the full analysis set who have no significant 
protocol deviations and met the inclusion/exclusion criteria.
Safety analysis set (SAF): including all patients who have received the study device.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 71 of 134
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
10.3
BASELINE DATA
Demographic and medical variables at baseline (including but not limited to, age, gender, race, 
job type (laborer/sedentary), medical history, medication history, and disease diagnosis) will be 
used to describe subjects and summarize subject information. Summary statistics will be given 
based on the nature of variables (continuous or categorical variables). Job role will be analyzed 
by Sedentary, Light, Medium and Heavy (heavy and very heavy) according to the US Social 
Security Administrations classification of labor by physical exertion requirements.
10.4
EFFICACY ANALYSIS
Analysis of Primary Endpoint
A binary variable will be defined based on whether each patient has a Sugaya score of Type IV 
or V retear/recurrence. This variable will be used to present the number of retears at the 6 month 
post-operative visit, together with a percentage and 95% confidence interval for a single 
proportion (calculated using the Clopper-Pearson Exact method). 
To test whether ARCR augmented with REGENETEN is superior to ARCR alone, the null 
hypothesis is that the retear rate of the ARCR augmented with REGENETEN group is not better 
than, or the same as, the retear rate of the ARCR alone group (standard of care):: 
H0: 
-
0  
0
H1
-
0  < 0
In the stated hypothes
tear for those patients which received 
REGENETEN and 
0 represents the rate of retear for the standard of care group. A binary 
variable of success/failure will be created to fit a logistic model adjusting for differences in 
baseline characteristics. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 72 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
As a further analysis of the primary endpoint, the time taken for retear to occur will be assessed 
as a survival endpoint for both treatment groups in order to compare the trend of incidence of 
retear over time.
Analysis will be carried out using the FAS and PP population.
Analysis of Secondary Endpoints
The following secondary endpoints will be analyzed for this study:
Retear rate at 3, 12 and 24 months post-operative will be summarized and presented as 
per the Primary Endpoint analysis.
OSS, WORC/C-WORC, Constant, SSV and EQ-5D-5L PRO scores will be calculated 
and summarized for each visit using descriptive statistics for continuous variables, 
separately for the ARCR augmented with REGENETEN group and the ARCR alone 
(standard of care) group. Changes from baseline to each subsequent follow up visit will 
be similarly summarized. Repeated measures ANCOVA models will be used to assess 
statistical significance in the change from baseline to each time point. The null 
hypothesis will be that there is no difference between baseline and the respective time 
point. An estimate of the LS mean difference between the time points for the scores will 
be reported, along with the corresponding 95% confidence interval and p-value. A 
separate model will be used to assess statistical significance between the treatment 
groups at each time point. Minimal Clinically Important Differences will be assessed and 
presented where appropriate.
Patient satisfaction and return to work questionnaire will be presented as number and 
percentage of patients who have selected each of the responses at each time point. The 
duration a patient has taken away from work will be summarized descriptively.
VAS Pain score (1-100mm) will be summarized at baseline, 2 and 6 weeks, 3, 6, 12 and 
24 months using descriptive statistics for continuous variables. Change from baseline to 
each follow up assessment will be similarly summarized and p-values will be presented. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 73 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
MRI analysis will be conducted by an external vendor at baseline, 3, 6, 12 and 24 months 
and will be presented appropriately for continuous or categorical variables. 
Opioid use will be collected each day for 2 weeks following surgery. The number of days 
of opioid use will be calculated for each patient and this will be presented descriptively for 
all patients, by treatment type (ARCR augmented with REGENETEN or ARCR alone).
Total operative time will be calculated for each treatment arm and presented 
descriptively. 
The type of sling will be collected and presented for each treatment arm summarizing if 
standard sling, shoulder immobilizer, abduction sling, ER sling, or other were advised 
and mobilization time will be calculated for both arms summarizing mobilization duration.
Analysis of Other Endpoints
A logistic regression model will be used to evaluate retear rates in at-risk groups at each time 
point. The following binary variables will be created and included in the final model: 
Age (>65 years vs 
65 years)
Diabetic status (diabetic vs not diabetic)
Smoking status (smoker vs non-smoker)
Blood pressure (hypertensive vs not hypertensive)
Job role (heavy laborer vs not heavy laborer)
The safety and efficacy in the revision repair subject group and at-risk groups will be 
summarized and presented as per the Secondary Endpoint analysis.
The following health economic evidence endpoints will be analyzed for this study:
o
Aggregate health care utilization costs; 
o
Number of unscheduled visits;
o
Reoperation rate;

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 74 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
o Surgeon recommendation for reoperation, type of surgery; 
o Time of operation to time of retear; 
o Level of service (LOS): In the case of reoperation: How many nights did the 
subject spend in the hospital as a result of surgery? 0, 1, 2, 3, 4, 5, >5 
10.5
SAFETY ANALYSES
All safety endpoints will be summarized using the safety population.
 
Adverse Events
The number of subjects reporting: adverse events, serious adverse events, adverse device 
effects, serious adverse device effects, and unanticipated serious device effects will be 
summarized. In addition, for each adverse event, the following will be summarized: severity, the 
relationship to investigational device use, outcome and duration of the resolved adverse events 
and the duration of the adverse events at trial discontinuation. 
 
Device deficiencies
The number of device deficiencies and the number of patients reporting a device deficiency will 
be summarized as well as a summary of device deficiencies with the potential to cause SADE. 
Additional summaries of safety endpoints, if applicable, will be described in the SAP. 
10.6 
INTERIM ANALYSES 
A formal interim analysis will be conducted once 50% of the planned subjects reach the 6-month 
follow-up visit to assess how the relative performance of the two treatments differ over time.  

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 75 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
SAMPLE SIZE JUSTIFICATION
Using a group sequential design, a formal interim analysis will be conducted once 50% of the 
planned 260 subjects reach the 6-month follow-up at which point a sample size re-estimation will 
be performed along with options considered to terminate early for efficacy or futility or to 
increase sample size for power. Further details will be specified within the SAP.
The initial RCT power analysis is based on a Lan-
-Fleming) spending function 
with hypothesized retear incidence of 15% for REGENETEN and 30% for conventional ARCR 
with 80% power and 5% significance level.
The sample size of 260 RCT (130 ARCR augmented with REGENETEN and 130 ARCR alone) 
is based on a primary hypothesis of 50% reduction in retear rates. 
ADVERSE EVENTS AND DEVICE DEFICIENCIES
12.1
DEFINITIONS
The categories of AEs are shown in Table 12.1-1. The definitions for each of these categories 
are given in the subsequent sections.
Table 12.1-1: Categories of Adverse Events
NOT DEVICE-
RELATED
DEVICE- OR PROCEDURE-RELATED
NON-
SERIOUS
ADVERSE EVENT 
(AE)
ADVERSE DEVICE EFFECT 
(ADE)
SERIOUS
SERIOUS ADVERSE 
EVENT 
(SAE)
SERIOUS ADVERSE DEVICE EFFECT
(SADE) (SEE 12.1.3)
ANTICIPATED
UNANTICIPATED
ANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT 
UNANTICIPATED SERIOUS 
ADVERSE DEVICE EFFECT  

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
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Page: 76 of 134
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
(ASADE)
(USADE)
Adverse Event
An Adverse Event is any untoward medical occurrence, unintended disease or untoward clinical 
sign (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
causally related to the IP and whether anticipated or unanticipated.
Note 1: This definition includes events related to the IP, comparator or ancillary products. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to the IP
AE is used both to refer to AE which do not meet the definitions of Adverse Device Effects or 
Serious Adverse Events and as an umbrella term referring to adverse events of all 
classifications.
An AE can be any unfavorable and unintended sign (for example, an abnormal laboratory 
finding), symptom, or disease. For reporting purposes, emphasis is placed first and foremost on 
whether or not the event constitutes an untoward medical occurrence.
Adverse Device Effect
An Adverse Device Effect (ADE) is an adverse event that is related to the use of the IP. 
Note 1: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation or operation, or any malfunction of the 
investigational medical device. 
Note 2: This definition includes any event resulting from use error or from intentional misuse of 
the investigational medical device. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 77 of 134
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Note 3: This includes comparator or if the comparator is a medical device.
Not Related - An AE is considered to be not related to the use of an IP or the procedure when 
the effect is DEFINITELY UNRELATED to have any relationship to the use of the 
IP or the procedure;
Related 
An AE is considered to be related to the use of an IP or the procedure when there
is a POSSIBLE, or DEFINITE relationship between the AE and the use of the IP 
or the procedure.
An ADE is further categorized depending on whether the criteria in section 12.1.3 and 12.1.4 are 
met.
Serious Adverse Events and Serious Adverse Device Effects
An AE or ADE is considered a Serious Adverse Event (SAE) or Serious Adverse Device Effect 
(SADE) if, in the view of either the Investigator or the Sponsor, it led to any of the following:
a) death,
b) serious deterioration in the health of the subject, users or other persons as defined by 
one or more of the following:
1) a life-threatening illness or injury, or
2) a permanent impairment of a body structure or a body function including 
chronic disease, or
3) in-patient or prolonged hospitalization, or
4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,
c) foetal distress, foetal death or a congenital abnormality or birth defect including 
physical or mental impairment.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 78 of 134
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the study
protocol, without serious deterioration in health, is not considered a serious adverse event.
Anticipated/Unanticipated Serious Adverse Device Effect
An Unanticipated Serious Adverse Device Effect (USADE) is a serious ADE which by its nature, 
incidence, severity or outcome has not been identified in the current version of the risk analysis 
report. 
Guidance Regarding the Determination of Unanticipated Events:
During causality assessment activity, clinical judgement shall be used and the relevant 
Report shall be consulted, as all the foreseeable serious adverse events and the potential risks 
are listed and assessed there. The presence of confounding factors, such as concomitant 
medication/treatment, the natural history of the underlying disease, other concurrent illness or 
risk factors shall also be considered. [MEDDEV 2.7/3 Rev 3 Sec 8].
Note: An anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report (see Section 4.4 for 
details).
Severity 
The severity of every AE will be assessed by the PI or medically qualified site staff to whom the 
responsibility has been delegated and documented on the delegation of authority log. AE should 
be classified as mild, moderate, or severe, regardless of whether or not the AE are considered to 
be serious or non-serious. The classification should be based on the following definitions:
Mild -
An event is mild if the subject is aware of, but can easily tolerate the sign or 
symptom;

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 79 of 134
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This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Moderate -
An event is moderate if the sign or symptom results in discomfort significant 
enough to cause interference with the 
Severe -  
An event is severe if the sign or symptom is incapacitating and results in the 
inability to work or engage in their usual activities.
Device Deficiency
A Device Deficiency (DD) is an inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety or performance. 
Note: DD includes malfunctions, use errors and inadequacy in the information supplied by the 
manufacturer including labelling. 
Device deficiencies that did not lead to an adverse event but could have led to a medical 
occurrence
a. if either suitable action had not been taken, 
b. if intervention had not been made, or 
c.
if circumstances had been less fortunate, 
are considered Device Deficiencies with potential to cause SADE and shall be reported as 
specified in section 12.3.
12.2
AE CODING DICTIONARY 
AE coding for this study will be done per International Medical Device Regulators Forum
(IMDRF) AE Terminology Annex E 
Clinical Signs, Symptoms and Conditions.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
12.3 
REPORTING PROCEDURES 
AE of any kind and DD will be recorded in the applicable eCRF and source notes. The 
Investigator will evaluate all AE for relationship to the device and procedure, seriousness, and 
severity. DD will be evaluated for potential to cause SADE. The following timescales should be 
followed for the AE/DD information to be entered into the eCRF and reported to the Sponsor or 
designee (see Figure 12.3-1 and Figure 12.3-2): 
 
ADE and DD  without unreasonable delay 
 
SAE, SADE and DD with potential to cause SADE  immediately (i.e. within 24 hours of 
the investigator being informed about the event) 
For ADE and DD, details of the product/procedure related to the event will be included and 
where applicable, pictures taken of the device. The deficient product should be retained for 
return to Smith+Nephew unless it is contaminated (e.g., used dressings must not be retained). 
Updates to submitted information will be recorded in the eCRF according to the timescales 
above. 
All adverse events will be reviewed by a medically qualified person appointed by the Sponsor to 
determine which, if any, meet criteria for expedited reporting to the regulatory authorities.  
The investigator will inform the IRB/EC of adverse events according to the IRB/EC requirements.  
Depending on the nature of the adverse event, Smith+Nephew may request copies of the 
tests performed or other documentation related to the AE. If the subject was hospitalized, a copy 
of the discharge summary may be requested by Smith+Nephew and should be forwarded as 
soon as it becomes available. In certain cases, Smith+Nephew also may request a letter from 
the Investigator that summarizes the events related to the case. Refer to the ISF Sponsor 
Contact Information Sheet to report SAE, unanticipated SADE, anticipated SADE, and DD. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
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Version: 2.0, 08 Dec 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Figure 12.3-1: Evaluation and Reporting of Adverse Events 
 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 82 of 134 
 
 
 
 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Figure 12.3-2: Evaluation and Reporting of Device Deficiencies 
 
12.4 
UNBLINDING OF INVESTIGATIONAL PRODUCT 
Not applicable. 
12.5 
FOLLOW-UP OF SUBJECTS WITH ADVERSE EVENTS 
For subjects who are experiencing ongoing unresolved AE at the time of their study completion 
or early discontinuation from the study, it is recommended that the Investigator schedule an 
appropriate follow-up visit to determine the outcome of the event.  
Any additional data must be documented and available to the Sponsor who will determine 
whether the data need to be documented in the eCRF/Clinical Study Report. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
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contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
Ongoing Adverse Events at Study Discontinuation
AEs which are related to a study procedure or REGENETEN Implant system and are ongoing at 
end of 
participation: The event should be followed until it is either resolved or until 
the event has become chronic and is not expected to further improve based on the Investig
review of the event.
AEs which are not related to a study procedure or REGENETEN Implant system and are 
ongoing at end of 
participation should be followed for 30 days after discontinuation 
or if the AE is resolved, whichever is sooner.
At the time of data analysis (e.g., interim or final), an evaluation of ongoing events should take
place and be listed as ongoing in the safety table.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
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contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
INVESTIGATOR OBLIGATIONS
The Principal Investigators will comply with Good Clinical Practice (GCP), and all applicable 
regulatory requirements as outlined in Appendix 21.5 and 21.6 of this protocol.
In addition, the PI will ensure that the Financial Disclosure Statements will be completed by the 
PI and the Sub-Investigator upon entry into the study and as any changes that affect their 
financial disclosure status occur during the course of the study and up to one year after study 
completion.
SPONSOR AND MONITOR RESPONSIBILITIES
The Sponsor will designate a monitor to conduct the appropriate site visits at the appropriate 
intervals. The clinical investigation will be monitored to ensure that: the rights and wellbeing of 
the subjects are protected; the reported data are accurate, complete, and verifiable from the 
source documents; and the study is conducted in compliance with the currently approved 
protocol and amendment(s), if applicable, with GCP regulations, and with applicable regulatory 
requirements.
Detailed monitoring requirements will be documented in the Clinical Monitoring Plan for this 
study.
14.1
SITE QUALIFICATION VISIT
A site qualification visit may be performed by the Sponsor prior to the execution of a clinical 
agreement to ensure that all Investigators have the appropriate training, staff, facilities, and 
resources to adequately conduct the study.

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 85 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
14.2
SITE INITIATION VISIT
A site initiation visit to provide training on the specifics of the study, site obligations and 
expectations of study conduct will be performed by the Sponsor or qualified person designated 
by the Sponsor following the execution of the CTA and documented IEC approval. 
14.3
SPONSOR AUDITS AND REGULATORY INSPECTION
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.  
14.4
CLOSE-OUT VISIT
A study close-out visit will be performed by the Sponsor or designee to retrieve and account for 
all remaining clinical data and to resolve outstanding queries. During study close-out, the 
monitor will review investigator files to ensure required documents and records are on file, 
confirm the disposition of any other ancillary items used for the study, and review regulatory 
requirements regarding records retention and IEC reporting requirements. When no subjects 
have been included, a remote close-out visit may be conducted. 
PROTOCOL AMENDMENTS
Amendments should be made only in necessary cases once the study has started. Protocol 
amendments must be approved by the protocol signatories prior to submission to the IRB/IEC.
Protocol amendments need to be approved by the IRB/IEC and Regulatory Authority(ies), 
according to the applicable requirements prior to implementation at the site.
CONFIDENTIALITY OF THE STUDY
The confidentiality of this study and associated documents is governed by the terms of the 
Clinical Trial Agreement (CTA). 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 86 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
STATEMENTS OF COMPLIANCE
This clinical study will be performed in compliance with the ethical principles of the Declaration of 
Helsinki and ISO14155:2020 Clinical investigation of medical devices
Good Clinical Practice
(GCP) [37, 38, 46], and all applicable local Singapore, Hong Kong, China, United Kingdom, 
Germany, Switzerland, France, Canada, United States, Australia, New Zealand, Japan and 
Netherlands regulations. 
This clinical study will not commence until the required approval/favorable opinion from the 
IRB/IEC and/or regulatory authority has been obtained. Any additional requirements imposed by 
the IRB/IEC and/or regulatory authority will be followed.
Public/Products Liability Insurance has been purchased by Smith+Nephew plc. Worldwide and 
incorporates coverage for personal injury in respect of clinical studies. The Sponsor agrees to 
operate in good faith and in accordance with ABHI (Association of British Healthcare Industries) 
guidelines regarding compensation for injury arising in the course of clinical studies.
END OF STUDY
Should circumstances arise which require the termination of the entire study prior to its planned 
completion (e.g., safety concerns) or circumstances arise which mean the end of the 
participation of an individual site (e.g., departure of Investigator, non-compliance), then this will 
be undertaken according to the SOPs of the Sponsor. 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to other parties (Investigator, 
IRB/IEC, Sponsor and regulatory authorities). If the study is prematurely terminated or 
suspended, the Investigator will promptly inform the IRB/IEC and the study sites, and will provide 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 87 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
the reason(s) for the termination or suspension. Circumstances that may warrant termination or 
suspension include, but are not limited to:
Determination of unexpected, significant or unacceptable risk to participants
Demonstration of efficacy that would warrant stopping
Insufficient compliance with study protocol requirements
Data that are not sufficiently complete and/or evaluable
Determination of futility
Study may resume once concerns about safety, study protocol compliance, data quality are 
addressed and satisfy the Sponsor and IRB/IEC.
A specific study site in this multi-center study may also warrant termination under the following 
conditions: 
Non-compliance to GCP or protocol 
Failure to enroll subjects 
Major protocol deviations 
Inaccurate or incomplete data 
Unsafe or unethical practices 
Safety or performance considerations 
Investigator involuntarily discontinues participation in study 
PUBLICATION POLICY
19.1
PUBLICATION OF STUDY DATA
The preparation and submission for publication of manuscripts containing the study results shall 
be in accordance with a process determined by the Clinical Trial Agreements between the study 
Sponsor and participating institutions. The publication or presentation of any study results shall 
comply with all applicable privacy laws, including, but not limited to HIPAA.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 88 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
19.2 
DATA SHARING 
Smith+Nephew is committed to upholding the highest ethical and legal standards involved in 
conducting clinical trials. Smith+Nephew, therefore, supports the data sharing requirements of 
The International Committee of Medical Journal Editors (ICMJE) published on the 6th June 2017 
[47]. In accordance, Smith+Nephew will consider requests to share individual (de-identified) 
participant data that underlie the results of any interventional clinical trial, as presented from the 
1st July 2018 within an ICMJE associated journal. Requests made by researchers who provide a 
methodologically sound proposal will be considered. Requests may include data that underlie 
results presented in text, tables, figures, and appendices, together with data dictionaries. 
Availability of these data will begin nine months and end 36 months after article publication. Data 
supplied may only be used by the researcher(s) named in the approved research proposal for 
the purposes of achieving the aims of the analyses specified therein. All proposals should be 
directed to datasharing.gcs@smith-nephew.com. To gain access, data requestors will need to 
sign a data access agreement. 
 
 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 89 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
REFERENCES
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Americans - Opportunities for Action.www.boneandjointburden.org.
2. Meislin RJ, Sperling JW, Stitik TP. Persistent shoulder pain: epidemiology, 
pathophysiology, and diagnosis. Am J Orthop (Belle Mead NJ). 2005;34(12 Suppl):5-9.
3. Weinstein SI, Yelin EH, Watkins-Castillo SI. The Burden of Musculoskeletal Diseases in 
the United States. In:2014.
4. Ostor AJ, Richards CA, Prevost AT, Speed CA, Hazleman BL. Diagnosis and relation to 
general health of shoulder disorders presenting to primary care. Rheumatology (Oxford) 
2005;44:800 5.
5. Tekavec E, Jöud E, Rittner R, Mikoczy Z, Nordander C, Petersson IF, et al. Population
based consultation patterns in patients with shoulder pain diagnoses. BMC 
Musculoskelet Disord 2012;13:238.
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variation in the use of subacromial decompression and rotator cuff repair of the shoulder 
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primary health care: a cost-of illness study in Sweden. BMC Musculoskelet  Disord. 2012 
Feb 10;13:17.
9. Hsu J, Keener JD. Natural History of Rotator Cuff Disease and Implications on 
Management. Operative techniques in orthopaedics. 2015;25(1):2-9.
10. Sambandam SN, Khanna V, Gul A, Mounasamy V. Rotator cuff tears: An evidence 
based approach. World journal of orthopedics. 2015;6(11):902-918.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 90 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
11. Teunis T, Lubberts B, Reilly BT and Ring D. A systematic review and pooled analysis of 
the prevalence of rotator cuff disease with increasing age. J Shoulder Elbow Surg. 
2014;23(12):1913
1921. 
12. Athwal GS, Armstrong AD. Rotator Cuff Tears. Diseases & Conditions  
https://orthoinfo.aaos.org/en/diseases--conditions/rotator-cuff-tears/.
13. T E Farley, C H Neumann, L S Steinbach, A J Jahnke and S S Petersen. Full-thickness 
tears of the rotator cuff of the shoulder: diagnosis with MR imaging. American Journal of 
Roentgenology. 1992;158: 347-351. 
14. Zhang A., Montgomery S., Nigo S., Hame S., Wang J., Gamradt S. Analysis of Rotator 
Cuff Repair Trends in a Large Private Insurance Population. The Journal of Arthroscopic 
and Related Surgery, Vol 29, No 4 (April), 2013: pp 623-629. 
15. Smith+Nephew DOF. EA/SPM/REGENETEN/005/v1. In. An overview of the outcomes 
associated with the standard of care for the surgical treatment of rotator cuff tears2019. 
16. Smith+Nephew DOF. EA/SPM/REGENETEN/011//v1. In. An overview of the re-tear 
rates associated with the use of single-row and double-row repair as a standard of care 
for the surgical treatment of rotator cuff tears2020. 
17. Smith+Nephew DOF. EA/SPM/REGENETEN/012/v1. In. An overview of the revision 
rates associated with the standard of care for the surgical treatment of rotator cuff 
tears2020 
18. Bishop J, Klepps S, Lo IK, Bird J, Gladstone JN, Flatow EL. Cuff integrity after 
arthroscopic versus open rotator cuff repair: A prospective study. J Shoulder Elbow Surg. 
2006;15(3):290-299. 
19. Heuberer PR, Smolen D, Pauzenberger L et al. Longitudinal long-term magnetic 
resonance imaging and clinical follow-up after single-row arthroscopic rotator cuff repair. 
Am J Sports Med. 2017;45(6):1283-1288. 
20. Diebold G, Lam P, Walton J, Murrell GaJJ. Relationship between age and rotator cuff 
retear: a study of 1,600 consecutive rotator cuff repairs. 2017;99(14):1198-1205. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 91 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
21. Rashid MS, Cooper C, Cook J, Cooper D, Dakin SG, Snelling S, et al. Increasing age 
and tear size reduce rotator cuff repair healing rate at 1 year: Data from a large 
randomized controlled trial. Acta orthopaedica. 2017;88(6):606-11. 
22. Patel S, Gualtieri AP, Lu HH, Levine WN. Advances in biologic augmentation for rotator 
cuff repair. Annals of the New York Academy of Sciences. 2016;1383(1):97-114. 
23. Schlegel TF, Abrams JS, Bushnell BD, Brock JL, Ho CP. Radiologic and clinical 
evaluation of a bioabsorbable collagen implant to treat partial-thickness tears: a 
prospective multicenter study. J Shoulder Elbow Surg. 2018 27(2):242-251. 
24. Bokor DJ, Sonnabend D, Deady L et al. Evidence of healing of partial-thickness rotator 
cuff tears following arthroscopic augmentation with a collagen implant: a 2-year MRI 
follow-up. MLTJ. 2016;6(1):16-25. 
25. Smith+Nephew. REGENETEN Bioinductive Implant IFU. refer to 6.1.1.1 for current 
version. 
26. Smith+Nephew. REGENETEN Tendon Marker IFU. refer to 6.1.1.1 for current version. 
27. Smith+Nephew. REGENETEN Tendon Stabilizing Guide IFU. refer to 6.1.1.1 for current 
version. 
28. Smith+Nephew. REGENETEN Manual Placement Instruments IFU. refer to 6.1.1.1 for 
current version.
29. Smith+Nephew. REGENETEN Tendon Anchors IFU. refer to 6.1.1.1 for current version.
30. Smith+Nephew. REGENETEN Bone Anchors IFU. refer to 6.1.1.1 for current version. 
31. Smith+Nephew. REGENETEN Bioinductive Implant Placement Cannula IFU. refer to 
6.1.1.1 for current version 
32. 
With a Bioinductive Collagen Patch for Large and Massive Rotator Cuff Tears: 2-Year 
Safety and Clinical Outcomes. Am J Sports Med 2019;47(8):1901-1908. 
33. Van Kampen C, Arnoczky S, Parks P, et al. Tissue-engineered augmentation of a rotator 
cuff tendon using a reconstituted collagen scaffold: a histological evaluation in sheep. 
Muscles Ligaments Tendons J. 2013;3(3):229-235. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 92 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
34. Bokor DJ, Sonnabend DH, Deady L, et al. Healing of partial-thickness rotator cuff tears 
following arthroscopic augmentation with a highly porous collagen implant: a 5-year 
clinical and MRI follow-up. Muscles, Ligaments Tendons J 2019;9(3):338-347. 
35. McElvany MD, McGoldrick E, Gee AO, Neradilek MB, Matsen FA, 3rd. Rotator cuff 
repair: published evidence on factors associated with repair integrity and clinical 
outcome. Am J Sports Med. 2015;43(2):491-500.
36. World Medical Association. World Medical Association Declaration of Helsinki - Ethical 
Principles for Medical Research Involving Human Subjects.; 2013. 
37. International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
For Human Use (ICH). Integrated Addendum to ICH E6(R1): Guideline for Good Clinical 
Practice E6(R2). Vol Step 4; 2016. 
38. Cofield Classification of Rotator Cuff Tears (Cofield 1982).Cofield, Surg Gynec Obstet, 
154(5): 667-672, 1982 
39. The Oxford Shoulder Score (OSS): Scoring System for the Oxford Shoulder Score. 
(2014, September 18). Oxford University Innovation. Retrieved, January 14, 2020 from 
https://innovation.ox.ac.uk/outcome-measures/oxford-shoulder-score-oss/.  
40. Western Ontario Rotator Cuff (WORC) Index. (2019, August 29). Physiopedia, Retrieved 
January 14, 2020 from https://www.physio-
pedia.com/index.php?title=Western_Ontario_Rotator_Cuff_(WORC)_Index&oldid=22137
1. 
41. Constant-Murley Shoulder Outcome Score. Physiopedia. Retrieved January 14, 2020 
from https://www.physio-pedia.com/Constant-Murley_Shoulder_Outcome_Score. 
42. Scores/Evaluation/Questionnaires. Socratesorthos.com. Retrieved March 30, 2020 from 
http://socratesortho.com/wp-content/uploads/Scores-Evaluations1.pdf. 
43. Sugaya H, et al. Functional and Structural Outcome After Arthroscopic Full-Thickness 
Rotator Cuff Repair: Single-Row Versus Dual-Row Fixation. Arthroscopy. 2005 
Nov;21(11):1307-1316. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 93 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
44. Somerson JS, Hsu JE, Gorbaty JD, et al. Classifications in Brief : Goutallier Clasification 
of Fatty Infiltration of the Rotator Cuff Musculature. Clin Orthop Relat Res. 2016 
May;474(5):1328-1332.
45. Janssen, M.F., et al., Measurement properties of the EQ-5D-5L compared to the EQ-5D-
3L across eight patient groups: a multi-country study. Qual Life Res, 2013. 22(7): p. 
1717-27.
46. International Organization for Standardization. ISO14155:2020 Clinical Investigation of 
Medical Devices for Human Subjects -- Good Clinical Practice (Edition 3). 3rd ed.; 2020.
47. International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals; 2017.
APPENDICES
21.1
PROTOCOL AMENDMENTS
General Purpose
This amendment has been completed to update the inclusion criteria, visit schedule, correct 
some errors in statistical section and perform administrative changes. The total number of sites 
have also been increased to reflect the challenges of recruiting for this indication.
Rationale
Following discussions with the sites and internal reviewers, the rationale for the changes made 
are as follows:
Section
Change
Rationale
Authors
Abigail Murphy replaces 
Aleksandra Vidakovic as CSM
Administrative.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
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CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
1.2 Principal 
Investigator 
Signature Page 
 
1.2 Coordinating 
Investigator Approval
Reference to version date updated 
from V1.0 to V2.0 
ISO14155 revision updated from 
2011 to 2020
Administrative. 
1.3 
Sponsor Approval 
Update to Clinical Strategy and 
Regulatory Approvers 
Administrative.
2.0 Synopsis  
Study Product 
Corrected typographic error 
(PDLLA instead of PLDLA), 
clarified type of anchors (tendon 
and bone) as well as updated the 
slight difference in wording for 
study product indication depending 
on generation of product applicable 
to a site.
Administrative and clarificatory 
2.0  
Synopsis 
Number of study 
sites 
Increase from 20 to 30 planned 
sites
Response to more challenging 
recruitment climate. 
2.0 Synopsis 
Targeted global 
regions
Added Japan and Netherlands as 
potential countries 
Expanded targeted regions to 
fulfil 30 sites requirement. 
2.0 
Synopsis 
Inclusion Criteria and 
7.2 Inclusion Criteria 
Relaxed screening cut-off for tear 
size (final eligibility remains 
>/=3cm)  
 
Usual course of large or 
massive rotator cuff tear is to 
progress rather than improve. 
Investigators have reported 
seeing patients that had 
ineligible measurements in 
MRI but are actually large or 
massive tears once measured 
with the calibrated probe. 
Relaxing the screening cut-off 
reduces the chances of 
missing tears that are actually 
eligible per the tear size 
definition.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
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CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
2.0  
Synopsis 
Exclusion Criteria 
And  
7.3 Exclusion Criteria
re pregnant or 
 
Administrative. 
2.0  
Synopsis
Exclusion Criteria 
And  
7.3 Exclusion Criteria
currently involved in any injury 
litigation relating to the index 
Subjects who are 
currently involved in any injury 
litigation or workers compensation 
claims 
Language added for workers 
compensation which is 
applicable to some 
geographies involved in the 
study and broadened the 
coverage of injury litigation. 
This change was instituted to 
minimise potential impact of 
workers compensation. 
claims/injury litigation in patient 
reported outcomes. 
2.0  
Synopsis 
Exclusion Criteria 
And  
7.3 Exclusion Criteria
Subject that meets the 
definition of a Vulnerable Subject 
updated to Subject that meets the 
definition of a Vulnerable Subject 
 
Administrative. 
2.0 Synopsis 
Study Duration
Extended from 42 to 48 months   
Reflect extended recruitment 
period.
2.0 
Synopsis 
Secondary Endpoint 
Constant-Murley added at 3 month 
visit
Pain VAS Score added at baseline,
3 and 6 months 
Correct error in earlier protocol 
as pain outcome measures 
were not documented 
correctly.
2.0  
Synopsis 
 
Secondary Endpoint 
Removed MRI tendon findings of 
secondary endpoint  
It is not possible to assess 
whether a tear is symptomatic 
or not via MRI. 
2.0  
Synopsis 
 
Study Schedule 
 
Schedule of Event: 
Demographics/Medical History-
added BMI 
Reflect the actual requirements 
of the study endpoints. 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 96 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
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intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Return to Work Questionnaire: 
marked for screening visit as there 
is baseline info being collected 
here 
Constant Murley added to 3 month 
visit
VAS Pain Score: marked for 
baseline, 3 and 6 mos as this was 
missed in last version 
X-Ray and MRI to confirm eligibility 
criteria must be within 12 months of 
surgery (extended from 6 months) 
3.4 List of 
Abbreviations and 
Definitions
Added CM as Abbreviation for 
Constant-Murley 
Administrative 
4.2 Literature 
Summary 
The REGENETEN 
Bioinductive Implant system is 
natural healing response to 
stimulate new tendon growth and 
Implant system is designed to 
response to support new tendon 
growth and disrupt disease 
 
Maintain consistency with 
available literature. 
4.2 Literature 
Summary 
The ability to induce new 
tissue formation and limit tear 
progression may represent a 
significant advancement in the 
formation and limit tear progression 
may represent a significant 
advancement in the treatment of 
Used more precise term. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 97 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
4.3 Study Purpose 
used to support registration in 
China and post market clinical 
follow-up (PMCF) in Europe, 
Australia and New Zealand and 
reimbursement in relevant 
be used to support post market 
clinical follow-up (PMCF) and 
reimbursement in relevant 
 
Changes were made to reflect 
updates to the regulatory 
status of REGENETEN in the 
different geographies and 
subsequent update to its use 
of data. 
4.4.1 Indications 
Added specific indication wording 
for depending on which device 
generation is applicable to the 
study country. 
To be consistent with the IFU 
indications wording in the 
different versions. 
6.1.1.1 
Investigational 
Product(S), 
Description  
 
 
Updated IFU version in table 
format. 
The IFUs may be updated 
periodically, in which case, the 
latest version will be used as a 
guide. 
Administrative. 
6.3.1 Labelling of 
Investigational 
Product 
Europe, Canada, Australia and 
New Zealand added to list of 
countries where REGENETEN is a 
commercial product. 
Added Japan as a country where 
the product will be cleared/licensed 
before study enrolment. 
Added statement on how further 
regulatory status updates will be 
managed via TMP-CD-18-01. 
Changes were made to reflect 
updates to the regulatory 
status of REGENETEN in the 
different geographies and the 
subsequent labelling 
requirements.
 
 
Regulatory status updates will 
be expected during the 
duration of the study. This 
statement avoids the need for 
a protocol amendment for 
labelling requirement changes 
related to regulatory status 
updates.
6.5 Surgical 
Technique
The REGENETEN System should 
be used according to the surgical 
Administrative. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 98 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
technique and IFUs provided with 
the investigational device per 
Section 6.1.1.1 
(removed list of outdated IFUs)
7.1 Subject 
Population 
Increased site number to 30 and 
added Netherlands and Japan 
Updated with plan for new 
sites. 
7.2 Inclusion Criteria Relaxed screening cut-off for tear 
size (final eligibility remains 
>/=3cm)  
Usual course of large or 
massive rotator cuff tear is to 
progress rather than improve. 
Investigators have reported 
seeing patients that had 
ineligible measurements in 
MRI but are actually large or 
massive tears once measured 
with the probe. Relaxing the 
screening cut-off reduces the 
chances of missing tears that 
are actually eligible per the 
tear size definition.
7.5 Informed 
Consent
Reference to ISO14155 version 
updated from 2011 to 2020 version
Administrative. 
8.1 Study Design 
Added competent authority for 
Japan and updated number of sites 
to 30.
Increased total study duration from 
42 to 48 months. 
Updated with plan for new 
sites to achieve recruitment 
targets in the extended 
timeline.
8.1.1 
Study Flowchart 
The flow diagram has been 
updated to have the randomization 
process after performing repair and 
to include process for patients 
requiring re-operation. Title 
updated to Study Flowchart-Main 
Arms 
Updated per feedback from 
sites. Tears have to be 
repairable to be considered 
eligible to doing the 
randomization after the repair 
ensures we do not randomise 
a patient that will end up as a 
 Addition of 
process for revision repair 
added for clarity.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 99 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
8.1.2 
Study Flowchart
Created new flowchart for Revision 
Repair Group
Added in this version as this 
was missed in v1.0.
8.3.2 
Secondary Endpoints
 
Constant-Murley added at 3 month 
visit
Pain VAS Score added at baseline 
and 3 and 6 months
 
Removed MRI tendon findings of 
secondary endpoint 
Correct error in earlier protocol 
as pain outcome measures 
were not documented 
correctly.
 
 
It is not possible to assess 
whether a tear is symptomatic 
or not via MRI. 
8.4.1 
Increase planned sites from 20 to 
30. 
Updated with plan for new 
sites to expedite recruitment. 
8.4.2 
Removed statement about 
assignment of randomization 
number. 
Randomization number is 
actually not assigned by the 
system, only treatment group 
name is assigned.
9.1.1.1 
Study Procedures by 
Visit 
Schedule of Event: 
Demographics/Medical History/BMI 
added 
Return to Work Questionnaire: 
marked for screening visit as there 
is baseline info being collected 
here 
Constant Murley added to 3 month 
visit
VAS Pain Score: marked for 
baseline, 3 and 6 mos as this was 
missed in last version 
X-Ray and MRI to confirm eligibility 
criteria must be within 12 months of 
surgery (extended from 6 months)
Reflect the actual requirements 
of the study endpoints. 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 100 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
9.1.2 
Screening (Baseline) 
Visit 1 (Day -60 to 
Day-1) 
4. Other demographic information 
updated to include BMI 
5. Obtain MRI and X-Ray (must be 
within 12 months of surgery - 
extended from 6 months).  The tear 
size measurement may be 
provided by the radiography report 
or as determined by the 
Investigator. 
13. Have the subject complete 
Work Status for Return to Work 
Questionnaire 
14. Have the subject complete VAS 
pain questionnaire. 
Added BMI as this is part of 
the standard eCRF 
Demographics/Med Hx form. 
 
We expect tear to progress 
over time so there is very low 
risk that tear will be ineligible in 
size. Extending the timeframe 
means we can expand the 
recruitment pool as not all sites 
may repeat MRIs older than 6 
months if already scheduled 
for an ARCR. 
 
Return to Work Questionnaire: 
marked for screening visit as 
there is baseline info being 
collected here. 
 
 
VAS Pain Score: marked for 
baseline as this was missed in 
last version.
9.1.6 
Postoperative 
Follow-up Visit 5 (3 
Months [91 ± 15 
days)
Added the following: 
2. Have the subject complete VAS 
pain score
Added as point 3. Complete the 
Constant-Murley Questionnaire 
(Physician/Examiner completed 
portion) 
6. Have the subject complete the 
subjective part of Constant-Murley 
Questionnaire. 
The rest of the activities 
renumbered automatically.
 
 
VAS Pain Score and Constant-
Murley Questionnaire: marked 
for 3 months as these were 
missed in last version. 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 101 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
9.1.7 Postoperative 
Follow-Up Visit (6 
Months [182 ± 30 
days]) 
Added the following: 
2. Have the subject complete VAS 
pain score 
The rest of the activities 
renumbered automatically
VAS Pain Score marked for 3 
months as this was missed in 
last version. 
 
9.2.10 
Return to Work 
Questionnaire 
- 1 updated to. Were you working 
before surgery? Y/N 
If yes, what was your job type and 
nature of your work? 
- 3 updated to. Have you been able 
to return to the job you did before 
your surgery (doing the same 
activities)? Y/N 
a. If No, is there a particular reason 
activities? 
- 4. If RTW, did you feel ready to go 
back to work or did you have to 
take further time off due to shoulder 
pain or weakness? Y/N 
b. If so, how long? 
Wording updated to be 
consistent with Return to Work
questionnaire 
 
9.2.12 
Imaging 
Examinations 
The Baseline MRI must occur 
within 12 months (extended from 6  
months) of enrollment into this 
study.
We expect tear to progress 
over time so there is very low 
risk that tear will be ineligible in 
size with MRI older than 6 
months. Extending the 
timeframe means we can 
expand the recruitment pool as 
not all sites may repeat MRIs 
older than 6 months if already 
scheduled for an ARCR.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 102 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
9.2.12 
Imaging 
Examinations 
Removed one of the MRI 
secondary endpoints: Retear: 
Divided into symptomatic and 
asymptomatic 
Added Competent Authority for 
Japan
MRI cannot provide 
assessment on whether tear is 
symptomatic or not. 
 
 
Administrative. 
10.4.1 
Analysis of Primary 
Endpoint 
Reworded hypotheses, updated 
inequality signs on the hypothesis 
test, removed t-test from primary 
endpoint and added a logistic 
model instead 
T-test was removed as we do 
not have continuous data. 
Language updated to reflect 
superiority. 
10.4.2 Analysis of 
Secondary Endpoints
Baseline added below. 
MRI analysis will be conducted by 
an external vendor at baseline, 3, 
6, 12 and 24 months and will be 
presented appropriately for 
continuous or categorical variables.
Clarification. Endpoints will be 
compared to baseline. 
10.6 Interim 
Analyses 
Added underlined and removed 
strucktrough phrases: 
A formal interim analysis will be 
conducted once 50% of the 
planned subjects reach the 6-
month and 1 year follow-up visits to 
assess how the relative 
performance of the two treatments 
differ over time. 
 
To be consistent with wording 
of interim analyses elsewhere 
in the protocol. There is no 
plan to conduct another interim 
analysis at 1 year as the main 
endpoint is at 6 months. 
17 Statements of 
Compliance 
Reference to ISO14155 version 
updated from 2011 to 2020 version.
Added Japan and Netherlands. 
Administrative. 
20. References 
Updated references 25-31 by 
removing old version dates and 
referencing current versions of 
IFUs in 6.1.1.1
Administrative 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 103 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
21.1.1 Protocol 
Amendments 
General Purpose 
This amendment has been 
completed to update the inclusion 
criteria, visit schedule, correct 
some errors in statistical section 
and perform administrative 
changes. The total number of sites 
have also been increased to reflect 
the challenges of recruiting for this 
indication. 
Added to document this 
amendment 
21.1.2 Rationale 
Added table of rationale for 
changes made (refer to actual 
section) 
Added to document this 
amendment 
21.1.3 Effect on 
Study Status 
New section added 
The changes made with this 
protocol amendment allows the 
study to improve recruitment by 
expanding the patient pool in the 
screening stage so as not to miss 
large tears that appear smaller on 
MRI as well as increase in number 
of sites that can recruit to the study. 
Some changes were also added to 
reflect the patient reported 
outcomes that need to be collected 
at each visit. Finally, the statistical 
section has been updated to reflect 
that the study is an superiority 
study and has continuous 
variables. 
The database will be updated 
according to the new protocol once 
approved. 
Added to document this 
amendment 
21.1.4 Details 
This table 
Added to document this 
amendment 
21.1.5 
Approval/Notification 
Added: 
These updates will be submitted for 
REC/IRB approval. The changes 
Added to document this 
amendment 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 104 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
will only be implemented after 
REC/IRB approval confirmation.
21.2
Updated to be consistent with 
current IFU versions and to reflect 
there are three generations of 
device that are in use in the study
Administrative
21.5 Principal 
Investigator 
Obligations
References to ISO14155:2011 
update to ISO14155:2020
Administrative
Effect on Study Status 
The changes made with this protocol amendment allows the study to improve recruitment by 
expanding the patient pool in the screening stage so as not to miss large tears that appear 
smaller on MRI as well as increase in number of sites that can recruit to the study. Some 
changes were also added to reflect the patient reported outcomes that need to be collected at 
each visit. Finally, the statistical section has been updated to reflect that the study is an 
superiority study and has continuous variables.
The database will be updated according to the new protocol once approved.
Details
The following revisions were made:
Section
Current Text 
Protocol Version 1.0  
Dated 16/APR/2020
Revised Text 
Protocol Version 2.0 
Dated 08/DEC/2021
Authors
Aleksandra Vidakovic, Clinical Study 
Manager
Abigail Murphy, Clinical Study 
Manager

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 105 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
1.1 Principal 
Investigator 
Signature Page 
and 
1.2 Coordinating 
Investigator 
Approval 
I have read the attached protocol 
-center, 
Randomized Controlled Study to 
Evaluate the Safety and Efficacy of 
ARCR augmented with 
System  in Full-thickness Tears (large 
or massive) Repair versus ARCR 
and agree to abide by all provisions 
set forth herein. 
I agree to comply with the 
Section 21.5 Principal Investigator 
Obligations (ISO14155:2011) and 
Section 21.6 Responsibilities of 
Clinical Trial Institution and 
Investigator (cFDA). 
I have read the attached protocol 
-center, 
Randomized Controlled Study to 
Evaluate the Safety and Efficacy of 
ARCR augmented with 
System  in Full-thickness Tears (large 
or massive) Repair versus ARCR 
alo
08Dec2021, and agree to abide by all 
provisions set forth herein. 
I agree to comply with the 
Section 21.5 Principal Investigator 
Obligations (ISO14155:2020) and 
Section 21.6 Responsibilities of 
Clinical Trial Institution and 
Investigator (cFDA). 
1.3  
Sponsor Approval 
Cristin Taylor, Global Clinical Strategy 
Lead
Kerry Geng, Head of Regulatory 
Affairs and Quality, Great China 
Lori Fontaine, Global Clinical Strategy 
Lead 
Jenna Horsley 
Sr Manager Regulatory Affairs, SPM 
and ENT
2.0 Synopsis 
Study Product
REGENETEN Bioinductive Implant 
s comprised of disposable 
instruments, a resorbable bovine 
collagen scaffold, poly-l/d-lactide 
(PLDLA) anchors to secure the 
scaffold to the underlying tendon, and 
PEEK anchors to secure the implant 
to bone. REGENETEN is indicated for 
the management and protection of 
tendon injuries in which there has 
been no substantial loss of tendon 
tissue.
REGENETEN Bioinductive Implant 
s comprised of disposable 
instruments, a resorbable bovine 
collagen scaffold, poly-l/d-lactide 
(PDLLA) tendon anchors to secure 
the scaffold to the underlying tendon, 
and PEEK bone anchors to secure 
the implant to bone. REGENETEN is 
indicated for the management and 
protection of tendon injuries/rotator 
cuff tendon injuries (see Indications 
Section 4.4.1) in which there has 
been no substantial loss of tendon 
tissue.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 106 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
2.0 Synopsis 
Number of study 
sites 
Up to 20 study sites 
Up to 30 study sites 
2.0 Synopsis 
Targeted global 
regions 
Singapore, Hong Kong, China, United 
Kingdom, Germany, Switzerland, 
France, Canada, Australia, New 
Zealand and United States sites.
Singapore, Hong Kong, China, United 
Kingdom, Germany, Switzerland, 
France, Canada, Australia, 
Netherlands, Japan, New Zealand 
and United States sites.
2.0 Synopsis 
Inclusion Criteria  
Subjects with a diagnosis of a 
symptomatic primary or recurrent 
(revision repair subject group), large 
measured on MRI and confirmed on 
arthroscopy using a calibrated probe) 
of the supraspinatus and/or 
infraspinatus tendons amenable to 
repair;  
Subjects with a diagnosis of a 
symptomatic primary or recurrent 
(revision repair subject group), large 
 3 cm AP/ML) of 
the supraspinatus and/or 
infraspinatus tendons amenable to 
repair. For screening purposes, a 
2 cm AP/ML tear as measured on 
MRI will be eligible to proceed to the 
operative visit but will have to be 
 3 cm on arthroscopy 
using a calibrated probe to proceed;
2.0 Synopsis 
Exclusion Criteria
14. Subject who is pregnant or 
breastfeeding
14. Subjects who are pregnant and 
breastfeeding
2.0 Synopsis 
Exclusion Criteria
Subjects who are currently involved in 
any injury litigation relating to the 
index shoulder
Subjects who are currently involved in 
any injury litigation or workers 
compensation claims
2.0 Synopsis 
Exclusion Criteria
20. Subject that meets the definition 
of a Vulnerable Subject per 
ISO14155:2011 Section 3.44. 
20. Subject that meets the definition 
of a Vulnerable Subject per 
ISO14155:2020 Section 3.44. 
2.0 Synopsis 
Study Duration 
42 months (18 month enrollment 
period and 24 months follow-up 
period). 
48 months (24 month enrollment 
period and 24 months follow-up 
period).
2.0 Synopsis 
Secondary Endpoint
Overall performance of full-thickness 
ARCR augmented with REGENETEN 
versus ARCR alone at Baseline and 
at 3, 6, 12 and 24 months assessed 
by:
Overall performance of full-thickness 
ARCR augmented with REGENETEN 
versus ARCR alone at Baseline and 
at 3, 6, 12 and 24 months assessed 
by: 
 
Constant-Murley Score (CM) 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 107 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Constant-Murley Score 
(except at 3 months) 
Pain, Visual analog scale 
(VAS) Score (additionally at 2 
and 6 weeks); 
 
Pain, Visual analog scale 
(VAS) Score (additionally at 
baseline, 2 weeks, 6 weeks, 3 
months and 6 months); 
2.0 Synopsis 
Secondary Endpoint
MRI Tendon Findings in ARCR 
augmented with REGENETEN versus 
ARCR alone postoperatively at 3, 6, 
12 and 24 months including 
o Sugaya score, 
o Goutallier grading, 
o Total tendon thickness, 
tendon length, 
o Retear: Divided into 
symptomatic and 
asymptomatic 
 
MRI Tendon Findings in ARCR 
augmented with REGENETEN versus 
ARCR alone postoperatively at 
Baseline, 3, 6, 12 and 24 months 
including
o Sugaya score, 
o Goutallier grading, 
o Total tendon 
thickness, tendon 
length, 
o Retear: Divided into 
symptomatic and 
asymptomatic 
2.0 Synopsis 
Study Schedule 
Schedule of Event: 
Demographics/Medical History 
Return to Work Questionnaire 
 
 
Constant-Murley 
 
VAS Pain Score 
 
X-Ray and MRI to confirm eligibility 
criteria must be within 6 months of 
surgery
Schedule of Event: 
Demographics/Medical History/BMI 
 
Return to Work Questionnaire: 
marked for screening visit as there is 
baseline info being collected here 
 
Constant-Murley added to 3-month 
visit 
 
VAS Pain Score: marked for baseline, 
3 months and 6 mos as this was 
missed in last version 
X-Ray and MRI to confirm eligibility 
criteria must be within 12 months of 
surgery

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 108 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
3.4 List of 
Abbreviations and 
Definitions 
Abbreviation: Constant  
Definition: Constant-Murley
Abbreviation: Constant/CM 
Definition: Constant-Murley
4.2 Literature 
Summary
The REGENETEN Bioinductive 
Implant system is designed to 
stimulate 
response to support new tendon 
growth and disrupt disease 
progression 
The REGENETEN Bioinductive 
Implant system is designed to support
to support new tendon growth and 
disrupt disease progression 
4.2 Literature 
Summary 
The ability to induce new tissue 
formation and limit tear progression 
may represent a significant 
advancement in the treatment of 
rotator cuff lesions. 
The ability to induce new tissue 
formation and limit tear progression 
may represent a significant 
advancement in the treatment of 
rotator cuff tears. 
4.3 Study Purpose 
The study results will be used to 
support registration in China and post 
market clinical follow-up (PMCF) in 
Europe, Australia and New Zealand 
and reimbursement in relevant 
countries.
The study results will be used to 
support post market clinical follow-up 
(PMCF) and reimbursement in 
relevant countries. 
4.4.1 Indications 
The REGENETEN Bioinductive 
Implant System (compromised of 
disposable instruments, a resorbable 
collagen implant, anchors to secure 
the scaffold to the underlying tendon 
and PEEK anchors to secure implant 
to the bone) is indicated for the 
management and protection of rotator 
cuff in which there has been no 
substantial loss of tendon tissue. 
The REGENETEN Bioinductive 
implant System has different 
indications depending on the country 
and shown below:
Singapore, Hong Kong, United 
States: The REGENETEN 
Bioinductive Implant System 
(compromised of disposable 
instruments, a resorbable collagen 
implant, anchors to secure the 
scaffold to the underlying tendon and 
PEEK anchors to secure implant to 
the bone) is indicated for the 
management and protection of 
tendon injuries which there has been 
no substantial loss of tendon tissue. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 109 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
China, United Kingdom, Germany, 
Switzerland, France, Canada, 
Australia, Netherlands, Japan New 
Zealand: The REGENETEN 
Bioinductive Implant System 
(compromised of disposable 
instruments, a resorbable collagen 
implant, anchors to secure the 
scaffold to the underlying tendon and 
PEEK anchors to secure implant to 
the bone) is indicated for the 
management and protection of rotator 
cuff tendon injuries which there has 
been no substantial loss of tendon 
tissue.
6.1.1.1 
Investigational 
Product(S), 
Description  
Old IFU versions 
Updated IFU version in table format. 
The IFUs may be updated 
periodically, in which case, the latest 
version will be used as a guide.
6.3.1 Labelling of 
Investigational 
Product 
The REGENETEN Bioinductive 
Implant System is an investigational 
product in China. Addition labels will 
be included on the commercial 
packaging to specify that the product 
is for clinical trial use only in order to 
meet regulatory requirements for use 
of investigational devices.
 
In the United States, Singapore and 
Hong Kong the REGENETEN 
Bioinductive Implant System is a 
commercial product and will be used 
as cleared/licensed. Product labeling 
will be the same as per standard 
commercial packaging.  
In Europe, Canada, Australia and 
New Zealand the REGENETEN 
Bioinductive Implant System is a 
product that will be cleared/registered 
before study enrollment. The product 
The REGENETEN Bioinductive 
Implant System is an investigational 
product in China. Addition labels will 
be included on the commercial 
packaging to specify that the product 
is for clinical trial use only in order to 
meet regulatory requirements for use 
of investigational devices.
In the United States, Singapore, 
Hong Kong, Europe, Canada, 
Australia and New Zealand, the 
REGENETEN Bioinductive Implant 
System is a commercial product and 
will be used as cleared/licensed. 
Product labeling will be the same as 
per standard commercial packaging. 
In Japan, the REGENETEN 
Bioinductive Implant System is a 
product that will be cleared/registered 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 110 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
will only be used either through 
market approval and/or special 
access approval.  
 
For China only, labels on the 
REGENETEN Bioinductive Implant 
System contain the following 
information in addition to standard 
commercial packaging:  
 
 
 
before study enrollment. The product 
will only be used either through 
market approval and/or special 
access approval. 
For China only, labels on the 
REGENETEN Bioinductive Implant 
System contain the following 
information in addition to standard 
commercial packaging: 
 
Study number, 
 
Clinical Investigation Use 
Only. 
Any regulatory status updates that 
may impact labeling requirements 
moving forward will be managed via 
TMP-CD-18-01 Investigational 
Products/Ancillary Products/Supplies 
Protocol.
6.5 Surgical 
Technique 
The REGENETEN System should be 
used according to the surgical 
technique and IFUs provided with the 
investigational device
List of outdated IFUs follow
The REGENETEN System should be 
used according to the surgical 
technique and IFUs provided with the 
investigational device per Section 
6.1.1.1
 
(removed list of outdated IFUs) 
7.1 Subject 
Population 
Up to 300 subjects will be enrolled 
into the study in up to 20 sites in the 
United States, Canada, United 
Kingdom, France, Switzerland, 
Germany, China, Singapore, Hong 
Kong, Australia and New Zealand:  
Up to 300 subjects will be enrolled 
into the study in up to 30 sites in the 
United States, Canada, United 
Kingdom, France, Switzerland, 
Germany, China, Singapore, Hong 
Kong, Australia, New Zealand, Japan 
and Netherlands  
7.2 Inclusion Criteria Subjects with a diagnosis of a 
symptomatic primary or recurrent 
(revision repair subject group), large 
Subjects with a diagnosis of a 
symptomatic primary or recurrent 
(revision repair subject group), large 
3 cm AP/ML) of 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 111 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
measured on MRI and confirmed on 
arthroscopy using a calibrated probe) 
of the supraspinatus and/or 
infraspinatus tendons amenable to 
repair.
 
the supraspinatus and/or 
infraspinatus tendons amenable to 
repair. For screening purposes, a 
2 cm AP/ML tear as measured on 
MRI will be eligible to proceed to the 
operative visit but will have to be 
 3 cm on arthroscopy 
using a calibrated probe to proceed.
7.3 Exclusion 
Criteria 
Subject who is pregnant or breast 
feeding. 
Subjects who are pregnant or breast 
feeding. 
7.3 Exclusion 
Criteria 
Subjects who are currently involved in 
any litigation relating to the index 
shoulder 
Subjects who are currently involved in 
any litigation or workers 
compensation claims. 
7.3 Exclusion 
Criteria 
Subject that meets the definition of a 
Vulnerable Subject per 
ISO14155:2011 Section 3.44. 
Subject that meets the definition of a 
Vulnerable Subject per 
ISO14155:2020 Section 3.44. 
7.5 Informed 
Consent 
Before conducting any study related 
procedures, informed consent shall 
be obtained from all participating 
subjects according to ISO14155:2011 
guidelines or applicable NMPA 
requirements in China.
Before conducting any study related 
procedures, informed consent shall 
be obtained from all participating 
subjects according to ISO14155:2020 
guidelines or applicable NMPA 
requirements in China.
8.1 Study Design 
This clinical trial is supporting the 
registration of a medical device in 
China and will support the post 
market clinical follow up in Europe, 
Australia and New Zealand after 
market approval and reimbursement 
to relevant countries and therefore is 
required to follow the requirements of 
relevant regulations issued by NMPA, 
MHRA, EMA, TGA, Medsafe, 
HealthCanada or FDA. 
 
Study duration is planned to take 
approximately 42 months (18-month 
enrollment and 24-month follow-up).  
This clinical trial is supporting the 
registration of a medical device in 
China and will support the post 
market clinical follow up in Europe, 
Australia and New Zealand after 
market approval and reimbursement 
to relevant countries and therefore is 
required to follow the requirements of 
relevant regulations issued by NMPA, 
PMDA, MHRA, EMA, TGA, Medsafe, 
HealthCanada or FDA. 
Study duration is planned to take 
approximately 48 months (24-month 
enrollment and 24-month follow-up).  

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 112 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
For primary hypothesis a total of up to 
260 subjects (130 ARCR augmented 
with REGENETEN; 130 ARCR alone) 
and additionally up to 40 revision 
repair subjects if applicable, for sub-
group analysis are planned to be 
included in up to 20 study sites.
For primary hypothesis a total of up to 
260 subjects (130 ARCR augmented 
with REGENETEN; 130 ARCR alone) 
and additionally up to 40 revision 
repair subjects if applicable, for sub-
group analysis are planned to be 
included in up to 30 study sites.
8.1.1 
Study Flowchart 
Original Flowchart 
The flow diagram has been updated 
to have the randomization process 
after performing repair and to include 
process for patients requiring re-
operation.  
Title updated to Study Flowchart-
Main Arms 
8.1.2 Study 
Flowchart 
NA
Created new flowchart for Revision 
Repair Group 
8.3.2 
Secondary 
Endpoints 
 
-Constant Murley (except at 3 
months) 
-Pain VAS score frequency at 2 & 6 
weeks
- MRI Tendon Findings in ARCR 
augmented with REGENETEN versus 
ARCR alone postoperatively at 3, 6, 
12 and 24 months 
- Retear: Divided into symptomatic 
and asymptomatic  
-Constant Murley  
-Pain VAS score frequency updated 
to include baseline, 2 weeks, 6 
weeks, 3 months and 6 months 
- MRI Tendon Findings in ARCR 
augmented with REGENETEN versus 
ARCR alone postoperatively at 
Baseline, 2 weeks, 6 weeks, 12 
months and 24 months 
- Retear: Divided into symptomatic 
and asymptomatic 
8.4.1 
In this study, subjects will be enrolled 
at multiple sites, utilizing up to 20 
sites globally. 
In this study, subjects will be enrolled 
at multiple sites, utilizing up to 30 
sites globally. 
8.4.2 
A randomization number will be 
assigned only when subject has 
signed the ICF and satisfied all study 
eligibility criteria.
Randomization will occur and a 
treatment will be assigned only when 
subject has signed the ICF and 
satisfied all study eligibility criteria.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 113 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
9.1.1-1 
Study Procedures 
by Visit 
Schedule of Event: 
Demographics/Medical History 
Return to Work Questionnaire 
 
Constant Murley
 
VAS Pain Score 
 
X-Ray and MRI to confirm eligibility 
criteria must be within 6 months of 
surgery 
Schedule of Event: 
Demographics/Medical History/BMI 
Return to Work Questionnaire: 
marked for screening visit as there is 
baseline info being collected here 
Constant Murley added to 3 month 
visit 
 
VAS Pain Score:  added for baseline, 
3 months and 6 months. 
 
X-Ray and MRI to confirm eligibility 
criteria must be within 12 months of 
surgery
9.1.2 
Screening 
(Baseline) Visit 1 
(Day -60 to Day-1) 
4. Other Demographic information 
 
5.Obtain MRI and X-Ray (must be 
within 6 months of surgery) 
 
 
 
 
 
 
13. Instruct the subject to return for 
the Operation Visit on the scheduled 
date.
4. Other demographic information 
updated to include BMI 
5. Obtain MRI and X-Ray (must be 
within 12 months of surgery).  The 
tear size measurement may be 
provided by the radiography report or 
as determined by the Investigator.
13. Have the subject complete Work 
Status for Return to Work 
Questionnaire 
14. Have the subject complete VAS 
pain questionnaire. 
15. Instruct the subject to return for 
the Operation Visit on the scheduled 
date. 
9.1.6 
 
Added the following: 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 114 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Postoperative 
Follow-up Visit 5 (3 
Months [91 ± 15 
days) 
No VAS and Constant-Murley 
Questionnaire 
2. Have the subject complete VAS 
pain score 
3. Complete the Constant-Murley 
Questionnaire (Physician/Examiner 
completed portion) 
6. Have the subject complete the 
subjective part of Constant-Murley 
Questionnaire. 
The rest of the activities re-numbered 
automatically. 
9.1.7 Postoperative 
Follow-Up Visit (6 
Months [182 ± 30 
days]) 
 
No VAS  
Added the following: 
2. Have the subject complete VAS 
pain score 
The rest of the activities renumbered 
automatically.
9.2.10 
Return to Work 
Questionnaire 
1. Where you working before 
surgery? Y/N  
a. If yes, what was your job and does 
your job require heavy lifting? 
2. Have you returned to work? Y/N  
a. If yes, how long after your 
operation did you return to work or if 
there a particular reason?  
3. Have you been able to return to the 
job you did before your injury/surgery 
(doing the same activities)? Y/N  
 
 
1.
Were you working before 
surgery? Y/N 
a. If yes, what was your job type 
and  
b. the nature of your work? 
 
2. Have you returned to work? Y/N
a. If yes, how long after your 
operation did you return to work 
b.  
k 
was there a particular reason? 
 
 
 
 
3. Have you been able to return to 
the job you did before your 
surgery (doing the same 
activities)? Y/N 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 115 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
 
4. If RTW, did you feel ready to go 
back to work or did you have to take 
further time off due to shoulder pain 
or weakness? Y/N a. If so, how long? 
a. If No, is there a particular 
the same activities? 
 
4. If RTW, did you feel ready to go 
back to work physically ? Y/N 
 
 
 
5. Since returning to work, did you 
have to take further time off due 
to shoulder pain or weakness? 
Y/N 
a. If so, how long? 
9.2.12 
Imaging 
Examinations
The Baseline MRI must occur within 6 
months of enrollment into this study. 
The Baseline MRI must occur within 
12 months of enrollment into this 
study. 
9.2.12 
Imaging 
Examinations 
The following reviewer assessments 
will be performed for all MRIs 
collected post-OP throughout the 
study (for endpoint analysis): 
Sugaya score
Goutallier grading 
Total tendon thickness, tendon 
length 
Retear: Divided into symptomatic 
and asymptomatic 
Size of retear (anteroposterior 
[AP]/mediolateral [ML]) 
Shape of retear 
All MRI assessments are detailed in 
the Image Review Charter. All 
imaging data will be stored in 
electronic Digital Imaging and 
Communications in Medicine 
(DICOM) format at the site until they 
The following reviewer assessments 
will be performed for all MRIs 
collected post-OP throughout the 
study (for endpoint analysis): 
Sugaya score
 Goutallier grading 
 Total tendon thickness, tendon 
length 
 Retear: Divided into symptomatic 
and asymptomatic 
 Size of retear (anteroposterior 
[AP]/mediolateral [ML]) 
 Shape of retear 
All MRI assessments are detailed in 
the Image Review Charter. All 
imaging data will be stored in 
electronic Digital Imaging and 
Communications in Medicine 
(DICOM) format at the site until they 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 116 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
are no longer needed in case further 
evaluation by an independent 
centralized reviewer is requested by 
NMPA, MHRA, EMA, TGA, Medsafe, 
HealthCanada, or FDA. 
are no longer needed in case further 
evaluation by an independent 
centralized reviewer is requested by 
NMPA, PMDA, MHRA, EMA, TGA, 
Medsafe, HealthCanada, or FDA. 
10.4.1 
Analysis of Primary 
Endpoint 
The following hypotheses will be 
tested to establish the rate of 
operations in the ARCR augmented 
with REGENETEN group is strictly no 
worse (lower) than the ARCR alone 
(standard of care) group:  
 
-
 
-
 
epresents 
the rate of retear for those patients 
represents the rate of retear for the 
standard of care group. A one-sided t-
test with alpha = 0.025 will be used to 
evaluate the hypothesis and the 
corresponding 95% CIs will also be 
presented. 
As a further analysis of the primary 
endpoint, the time taken for retear to 
occur will be assessed as a survival 
endpoint for both treatment groups in 
order to compare the trend of 
incidence of retear over time. 
 
Analysis will be carried out using the 
PP population as the primary analysis 
population with the FAS population 
used for sensitivity analysis.
To test whether ARCR augmented 
with REGENETEN is superior to 
ARCR alone, the null hypothesis is 
that the retear rate of the ARCR 
augmented with REGENETEN group 
is not better than, or the same as, the 
retear rate of the ARCR alone group 
(standard of care): 
 - 
 
- 
 
 
the rate of retear for those patients 
which received REGENETEN a
represents the rate of retear for the 
standard of care group. A binary 
variable of success/failure will be 
created to fit a logistic model 
adjusting for differences in baseline 
characteristics.  
 
As a further analysis of the primary 
endpoint, the time taken for retear to 
occur will be assessed as a survival 
endpoint for both treatment groups in 
order to compare the trend of 
incidence of retear over time. 
Analysis will be carried out using the 
FAS and PP population. 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 117 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
10.4.2 Analysis of 
Secondary 
Endpoints 
MRI analysis will be conducted by an 
external vendor at 3, 6, 12 and 24 
months and will be presented 
appropriately for continuous or 
categorical variables.
MRI analysis will be conducted by an 
external vendor at baseline, 3, 6, 12 
and 24 months and will be presented 
appropriately for continuous or 
categorical variables.
10.6 Interim 
Analyses
A formal interim analysis will be 
conducted once the subjects reach 
the 6-month and 1 year follow-up 
visits to assess how the relative 
performance of the two treatments 
differ over time. 
A formal interim analysis will be 
conducted once 50% of the planned 
subjects reach the 6-month follow-up 
visit to assess how the relative 
performance of the two treatments 
differ over time.  
17. Statements of 
Compliance 
This clinical study will be performed in 
compliance with the ethical principles 
of the Declaration of Helsinki and 
ISO14155:2011 Clinical investigation 
of medical devices  Good Clinical 
Practice (GCP) [37, 38, 46], and all 
applicable local Singapore, Hong 
Kong, China, United Kingdom, 
Germany, Switzerland, France, 
Canada, United States, Australia and 
New Zealand regulations.  
This clinical study will be performed in 
compliance with the ethical principles 
of the Declaration of Helsinki and 
ISO14155:2020 Clinical investigation 
of medical devices  Good Clinical 
Practice (GCP) [37, 38, 46], and all 
applicable local Singapore, Hong 
Kong, China, United Kingdom, 
Germany, Switzerland, France, 
Canada, United States, Australia, 
New Zealand, Japan and Netherlands 
regulations.  
20. References 
25. Smith+Nephew. REGENETEN 
Bioinductive Implant IFU. Jan2018 
ed.; Rev C.  
26. Smith+Nephew. REGENETEN 
Tendon Marker IFU. Jan2018 ed.; 
Rev D.  
27. Smith+Nephew. REGENETEN 
Tendon Stabilizing Guide IFU. 
Jan2018 ed.; Rev E.  
28. Smith+Nephew. REGENETEN 
Manual Placement Instruments IFU. 
Jan2018 ed.; Rev B.  
48. Smith+Nephew. 
REGENETEN Bioinductive 
Implant IFU. refer to 6.1.1.1 
for current version. 
49. Smith+Nephew. 
REGENETEN Tendon Marker 
IFU. refer to 6.1.1.1 for current 
version. 
50. Smith+Nephew. 
REGENETEN Tendon 
Stabilizing Guide IFU. refer to 
6.1.1.1 for current version. 
51. Smith+Nephew. 
REGENETEN Manual 
Placement Instruments IFU. 
refer to 6.1.1.1 for current 
version.

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 118 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
29. Smith+Nephew. REGENETEN 
Tendon Anchors IFU. Jan2018 ed.; 
Rev D.  
30. Smith+Nephew. REGENETEN 
Bone Anchors IFU. Feb2018 ed.; Rev 
G. 
31. Smith+Nephew. REGENETEN 
Bioinductive Implant Placement 
Cannula IFU. Feb2018; RevC.  
52. Smith+Nephew. 
REGENETEN Tendon 
Anchors IFU. refer to 6.1.1.1 
for current version. 
53. Smith+Nephew. 
REGENETEN Bone Anchors 
IFU. refer to 6.1.1.1 for current 
version. 
54. Smith+Nephew. 
REGENETEN Bioinductive 
Implant Placement Cannula 
IFU. refer to 6.1.1.1 for current 
version 
21.1.1 Protocol 
Amendments 
General Purpose 
N/A 
This amendment has been completed 
to update the inclusion criteria, visit 
schedule, correct some errors in 
statistical section and perform 
administrative changes. The total 
number of sites have also been 
increased to reflect the challenges of 
recruiting for this indication.
21.1.2 Rationale 
N/A 
Added table of rationale for changes 
made (refer to actual section)
21.1.3 Effect on 
Study Status 
N/A 
The changes made with this protocol 
amendment allows the study to 
improve recruitment by expanding the 
patient pool in the screening stage so 
as not to miss large tears that appear 
smaller on MRI as well as increase in 
number of sites that can recruit to the 
study. Some changes were also 
added to reflect the patient reported 
outcomes that need to be collected at 
each visit. Finally, the statistical 
section has been updated to reflect 
that the study is an superiority study 
and has continuous variables. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 119 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
The database will be updated 
according to the new protocol once 
approved. 
21.1.4 Details of 
Protocol 
Amendment
N/A 
Added this table detailing changes 
made between the two versions 
21.1.5 
Approval/Notification
N/A
These updates will be submitted for 
REC/IRB approval. The changes will 
only be implemented after REC/IRB 
approval confirmation. 
21.2 
Smith+Nephew. REGENETEN 
Bioinductive Implant IFU. Jan2020 
ed.; Rev C. 
Smith+Nephew. REGENETEN 
Manual Placement Instruments 
IFU. Jan2018 ed.; Rev B. 
Smith+Nephew. REGENETEN 
Tendon Anchors IFU. Jan2018 ed.; 
Rev D. 
Smith+Nephew. REGENETEN 
Bone Anchors IFU. Feb2018 ed.; 
Rev G. 
Smith+Nephew. REGENETEN 
Bioinductive Implant Placement 
Cannula IFU. Feb2018; RevC.  
Smith+Nephew. REGENETEN 
Tendon Marker IFU. Jan2018 ed.; 
Rev D.
Smith+Nephew. REGENETEN 
Tendon Stabilizing Guide IFU. 
Jan2018 ed.; Rev E 
Updated to be consistent with current 
versions and to reflect there are three 
generations of device that are in use 
in the study. 
 
21.5 Principal 
Investigator 
Obligations 
PRINCIPAL INVESTIGATOR OBLIGATIONS 
(ISO14155:2011) 
PRINCIPAL INVESTIGATOR OBLIGATIONS 
(ISO14155:2020) 
Further references to 2011 version 
updated to 2020 elsewhere in the 
section 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 120 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
General comment: the protocol template was also updated over-all to include all the changes 
from TMP-CD-05 Rev A to current Rev D.1.
Approval/Notification
These updates will be submitted for REC/IRB approval. The changes will only be implemented 
after REC/IRB approval confirmation. 
21.2
INSTRUCTIONS FOR USE
Gen 3.5 US
Gen 3.5 Intl
Gen 3.0
Part
IFU Version
IFU Version
IFU Version
Bioinductive 
Implant 
02/2020 10601445 
Rev. D
02/2020 10601447 
Rev. B
02/2020 10601401 
Rev. C
Tendon Anchors
01/2019 10601404 
Rev. B
02/2020 10601391 
Rev. C
02/2020 10601391 
Rev. C
Bone Anchors
01/2019 10601405 
Rev. B
02/2020 10601392 
Rev. C
02/2020 10601392 
Rev. C
Tendon Stabilising 
Guide
10/2018 10601407 
Rev. A
02/2020 10601394 
Rev. C
02/2020 10601393 
Rev. C
21.3
EQUIPMENT AND SPECIAL INSTRUCTIONS
Clinical study sites and PIs should properly manage the surgical tools, investigational devices 
and test equipment in accordance with regulations of applicable guidelines and trial protocol. 
The clinical study sites and the PIs cannot use and permit the use of the investigational devices 
and test equipment for any purpose other than the implementation of this trial, and will follow 
applicable guidelines, trial protocol and any instructions given by the Sponsor regarding any 
operation, maintenance or storage of the investigational devices and test equipment. Upon 
termination or expiration of this Agreement, according to the Sponsor's choice, all unused 
investigational devices and test equipment should be returned to the Sponsor or be disposed 
according to the written instructions of the Sponsor. 

Study Protocol
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number:
REGENETEN.2020.01
Version: 2.0, 08 Dec
2021
Page: 121 of 134
CONFIDENTIAL AND PROPRIETARY
This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew. 
TMP-CD-05-01 
Clinical Protocol-Device 
Revision D.1; SOP-CD-05 Clinical Protocols
21.4
HEALTH ECONOMIC OUTCOME MEASURES/ QUALITY OF LIFE MEASURES
For reimbursement and health economic evidence following data will be collected additionally to 
endpoint related data, where possible:
1. Hospital length of stay including readmission, number of specialist clinic or physician, 
physiotherapy visits.
2. Unit costs of procedures or resource utilization where possible
Reoperation: 
1. Hospital readmissions (number of patients readmitted post-surgery and reasons for 
readmissions)
2. Number of specialist clinic or physician, physiotherapy visits
Unit costs of resource use where possible
Type of 
cost
Cost for
Specification/ 
Examples
Source of unit costs
Direct 
cost to the 
healthcare 
system or 
the patient
Primary care 
consultations
General practitioner, 
medical specialist, 
physiotherapist, 
chiropractor etc
Relevant National Reference 
costs
Secondary care 
consultations
Inpatient, emergency 
department, and 
outpatient services
Relevant National Reference 
costs
Diagnostic tests
MRI, CT scan, and X-ray
Relevant National Reference 
costs

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 122 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
Pharmaceutical 
treatment
Analgesic, NSAIDs, 
tramadol, (just as 
examples) 
Relevant National Reference 
costs 
Transportation 
Travel expenses for the 
patient
Mileage allowance according 
to the relevant country
Reoperation
Type of surgery, implant 
costs, material costs 
Relevant National Reference 
costs 
Indirect 
cost 
Absenteeism
Absence from work 
Mean wage according to 
Statistics of relevant country 
Presenteeism 
Reduced productivity at 
work due to rotator 
shoulder pain 
Mean wage according to 
Statistics of relevant country 
21.5 
PRINCIPAL INVESTIGATOR OBLIGATIONS (ISO14155:2020) 
1. General:  
a. 
The role of the PI is to implement and manage the day-to-day conduct of the clinical 
investigation as well as ensure data integrity and the rights, safety, and well-being of 
the subjects involved in the clinical investigation.  
2. Qualification of the PI. The PI shall: 
a. 
be qualified by education, training, and experience to assume responsibility for the 
proper conduct of the clinical investigation in accordance with this International 
Standard; evidence of such qualifications of the PI and key members of the 
investigation site team shall be provided to the Sponsor through up-to-date Curriculum 
Vitae (CV) or other relevant documentation, 
b. 
be experienced in the field of application and trained in the use of the investigational 
device under consideration, 
c. 
disclose potential conflicts of interest, including financial, that interfere with the conduct 
of the clinical investigation or interpretation of results, and

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 123 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
d. 
be knowledgeable with the method of obtaining informed consent. 
3. Qualification of investigation site. The PI shall be able to demonstrate that the proposed 
investigation site: 
a.
has the required number of eligible subjects needed within the agreed recruitment 
period, and 
b. 
has one or more qualified investigators, a qualified investigation site team and adequate 
facilities for the foreseen duration of the clinical investigation. 
4. Communication with the IEC. The PI shall:  
a. 
provide the Sponsor with copies of any clinical-investigation-related communications 
between the PI and the IEC, 
b. 
comply with the requirements described in 4.5 of ISO14155:2020. 
i. 
Submit to the IEC the following information, any amendments and any additional 
documentation required by the IEC: the Protocol; IB or equivalent; informed 
consent form and any other written information provided to subjects; procedures 
for recruiting subjects and advertising materials, if any; a copy of the CV of the 
PI(s) for with the IEC has oversight. 
ii. 
Provide documentation of the IECs approval/favorable opinion, identifying the 
documents and amendments on which the opinion was based, to the Sponsor, 
prior to commencing the clinical investigation.  
iii. 
Submit the following to the IEC if required by national regulations, the protocol or 
IEC, whichever is more stringent: 
1. 
SAEs 
2. 
Requests for deviations, and reports of deviations, if the deviation affects 
-being, or the scientific integrity of the clinical 
investigation. Document and report to the Sponsor and IEC a report of 
deviations made to protect the rights, safety, and well-being of human 
subjects under emergency circumstances.  
3. 
Progress reports, including safety summary and deviations 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 124 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
4. 
Amendments to any documents already approved by the IEC.  
5. 
If applicable, notifications of suspension or premature termination 
6. 
If applicable, justification and request for resuming the clinical investigation 
after suspension.  
7. 
Clinical investigation report or summary. 
iv.
As a minimum, during the clinical investigation, the following information shall be 
obtained in writing from the IEC prior to implementation: 
1. 
Approval/favorable opinion of amendments 
2. 
safety, and well-being or scientific integrity of the clinical investigation 
3. 
Approval for resumption of a suspended clinical investigation if applicable.  
c. 
obtain the written and dated approval/favorable opinion of the IEC for the clinical 
investigation before recruiting subjects and implementing all subsequent amendments, 
if required, 
d. 
promptly report any deviations from the protocol that affect the rights, safety or well-
being of the subject or the scientific integrity of the clinical investigation, including those 
which occur under emergency circumstances, if required by the IEC, protocol or 
national regulations. In particular circumstances, the communication with the IEC can 
be performed by the Sponsor, partly or in full, in which case the Sponsor shall keep the 
Principal Investigator informed. 
5. Informed consent process. The PI shall: 
a. 
General: 
i. 
Informed consent shall be obtained in writing from the subject and the process 
shall be documented before any procedure specific to the clinical investigation is 
applied to the subject; except when special circumstances for emergency 
treatments apply (see below) 
b. 
Process of obtaining informed consent. The general process for obtaining informed 
consent shall be documented in the protocol and shall comply with the following. These 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 125 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
requirements also apply with respect to informed consent obtained from a subject
legally authorized representative:  
i. 
Ensure that the PI or his/her authorized designee conducts the informed consent 
process 
ii. 
decision to participate throughout the clinical investigation
iii. 
Avoid any coercion or undue improper influence on, or inducement of, the subject 
to participate
iv. 
 
v. 
Use native non-technical language that is understandable to the subject 
vi. 
Provide ample time for the subject to read and understand the informed consent 
form and to consider participation in the clinical investigation 
vii. 
Include personally dated signatures and the PI or an authorized designee 
responsible for conducting the informed consent process 
viii. 
Show how informed consent will be obtained in special circumstances (see below) 
where the subject is unable to provide him or herself, and  
ix. 
Ensure important new information is provided to new and existing subjects 
throughout the clinical investigation.  
c.
Special circumstances for informed consent (the following provisions are subject to 
national regulations): 
i. 
Subject needing legally authorized representatives:  informed consent may be 
given by the legally authorized representative only if a subject is unable to make 
the decision to participate in a clinical investigation (e.g., infant, child, or juvenile, 
seriously ill or unconscious subject, mentally ill person, mentally handicapped 
person). In such cases, the subject shall also be informed about the clinical 
investigation within his/her ability to understand.  
ii. 
Subject unable to read or write: informed consent shall be obtained through a 
supervised oral process if a subject or legally authorized representative is unable 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 126 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
to read or write. An independent witness shall be present throughout the process. 
The written informed consent form and any other information shall be read aloud 
and explained to the prospective subject or his/her legally authorized 
representative and, whenever possible, either shall sign and personally date the 
informed consent form. The witness also signs and personally dates the informed 
consent for attesting that the information was accurately explained and that the 
informed consent was freely given.  
iii. 
Emergency treatments:  
1. 
For clinical investigations involving emergency treatments, when prior 
representative, if present, shall be requested.  
2. 
When it is not possible to obtain prior informed consent from the subject, and 
may still be enrolled if a specific process has been described in the protocol.  
3. 
Arrangements shall be made to inform the subject or legally authorized 
representative
clinical investigation and about all aspects of the clinical investigation.  
4.
The subject shall be asked to provide informed consent for continued 
participation as soon as his/her medical condition allows.  
d. 
The Principal Investigator may not enroll a subject without obtaining informed consent 
of the subject or his/her legally authorized representative only when the following 
conditions are fulfilled: the prospective subject fulfils the emergency conditions and is 
obviously in a life-threatening situation; no sufficient clinical benefits are anticipated 
from the currently available treatment; there is a fair possibility that the life-threatening 
risk to the prospective subject can be avoided if the investigational device is used; 
anticipated risks are outweighed by the potential benefits of applying the investigational 
device ; the legally authorized representative cannot be promptly reached and informed.  

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 127 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
e. 
Information provided to the subject. All information pertinent to the clinical investigation, 
including at least the following, shall be provided in writing and in native, non-technical 
language that is understandable to the su
authorized 
representative): 
i. 
Description and purpose 
ii.
Potential benefits
iii. 
Risks and inconveniences or the subject and, when applicable, for any embryo, 
fetus or nursing infant 
iv. 
Alternative procedures 
v. 
Confidentiality
vi. 
Compensation
vii. 
Anticipated expenses, if any, to be borne by the subject for participating in the 
clinical investigation 
viii. 
 
ix. 
Contact persons 
x. 
Statement declaring that new findings or the reasons for any amendment to the 
the subject. 
xi.
pation in the clinical investigation 
xii. 
Termination procedures 
f. 
Informed consent signature shall contain the following: 
i. 
The voluntary agreement to participate in the clinical investigation and follow the 
 
ii. 
A statement declaring that refusal of participation incurs no penalty for the subject 
iii. 
A statement declaring that discontinuation at any time incurs no penalty for the 
subject 
iv. 
A statement with regard to the possible consequences of withdrawal 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 128 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
v. 
An acknowledgment of the information provided and confirmation that all the 
 
vi. 
A statement confirming that the subject or his/her legally authorized 
purpose of the clinical investigation 
vii.
A statement confirming that the subject or his/her legally authorized 
 
g. 
New information: if new information becomes available that can significantly affect a 
subject(s) affected in written form. If relevant, all affected subjects shall be asked to 
confirm their continuing consent in writing.  
h. 
ensure compliance with the applicable regulatory requirements and ethical principles for 
the process of obtaining informed consent, and 
i. 
ensure and document appropriate training if an authorized designee is appointed to 
conduct the informed consent process. 
6. Compliance with the protocol. The Principal Investigator shall: 
a. 
indicate his/her acceptance of the protocol in writing, 
b.
conduct the clinical investigation in compliance with the protocol,
c. 
create and maintain source documents throughout the clinical investigation and make 
them available as requested during monitoring visits or audits, 
d. 
ensure that the investigational device is used solely by authorized users as specified in 
6.2, and in accordance with the protocol and instructions for use, 
e. 
propose to the Sponsor any appropriate modification(s) of the protocol or investigational 
device or of the use of the investigational device, 
f. 
refrain from implementing any modifications to the protocol without agreement from the 
Sponsor, IEC and regulatory authorities, if required, 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 129 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
g. 
document and explain any deviation from the approved protocol that occurred during 
the course of the clinical investigation, 
h. 
ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation, 
i. 
ensure that maintenance and calibration of the equipment relevant for the assessment 
of the clinical investigation is appropriately performed and documented, where 
applicable, 
j. 
ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
Sponsor in the CRF and in all required reports, 
k. 
maintain the device accountability records, 
l. 
allow and support the Sponsor to perform monitoring and auditing activities, 
m. be accessible to the monitor and respond to questions during monitoring visits, 
n. 
allow and support regulatory authorities and the IEC when performing auditing 
activities, 
o. 
ensure that all clinical-investigation-related records are retained as required taking 
measures to prevent accidental or premature destruction, and
p. 
review and sign the clinical investigation report, as applicable.
7. Medical care of subjects. The Principal Investigator shall 
a.
provide adequate medical care to a subject during and after a subject's participation in 
a clinical investigation in the case of adverse events,  
b. 
inform the subject of the nature and possible cause of any adverse events experienced, 
c. 
provide the subject with the necessary instructions on proper use, handling, storage, 
and return of the investigational device, when it is used or operated by the subject, 
d. 
inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required, 
e. 
provide the subject with well-defined procedures for possible emergency situations 
related to the clinical investigation, and make the necessary arrangements for 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 130 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
emergency treatment, including decoding procedures for blinded/masked clinical 
investigations, as needed, 
f. 
ensure that clinical records are clearly marked to indicate that the subject is enrolled in 
a particular clinical investigation, 
g. 
if appropriate, subjects enrolled in the clinical investigation shall be provided with some 
means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided), 
h. 
inform, with the subject's approval or when required by national regulations, the 
subject's personal physician about the subject's participation in the clinical investigation, 
and  
i. 
make all reasonable efforts to ascertain the reason(s) for a subject's premature 
withdrawal from the clinical investigation while fully respecting the subject's rights. 
8. Safety reporting. The Principal Investigator shall: 
a. 
record every adverse event and observed device deficiency, together with an 
assessment, 
b. 
report to the Sponsor, without unjustified delay, all serious adverse events and device 
deficiencies that could have led to a serious adverse device effect; this information shall 
be promptly followed by detailed written reports, as specified in the protocol,
c. 
c) report to the IEC serious adverse events and device deficiencies that could have led 
to a serious adverse device effect, if required by the national regulations or protocol or 
by the IEC, 
d. 
report to regulatory authorities serious adverse events and device deficiencies that 
could have led to a serious adverse device effect, as required by the national 
regulations, and 
e. 
supply the Sponsor, upon Sponsor's request, with any additional information related to 
the safety reporting of a particular event. 
 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 131 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
21.6 
RESPONSIBILITIES OF CLINICAL TRIAL INSTITUTION AND INVESTIGATOR (CFDA 
CHINA FOOD AND DRUG ADMINISTRATION) 
 
Article 59 Before accepting a clinical trial, the clinical trial institution shall assess relevant 
resources according to the characteristics of the investigational medical device to determine 
whether to accept that clinical trial.
Article 60 The clinical trial institutions shall properly keep the clinical trial records and basic 
documents as per the agreement with the sponsor. 
 
Article 61 The investigator who is responsible for the clinical trial shall meet the following 
conditions: 
(1) Having the professional technical titles and qualifications of deputy chief physician, 
associate professor and associate investigator in the clinical trial institution; 
(2) Having the expertise and experience required by the investigational medical device, 
and having accepted relevant training if necessary; 
(3) Familiar with the material and literatures related to the clinical trial required and 
provided by the sponsor; 
(4) Competent to coordinate, control and make use of the personnel and equipment to 
carry out the trial, and to deal with adverse events and other associated events that may 
be incurred by in the investigational medical device;
(5) Familiar with relevant state laws and regulations and this GCP.
 
 
Article 62 Before the clinical trial, the medical device clinical trial management department of 
the clinical trial institution shall coordinate with the sponsor to submit the application to the 
ethics committee and submit relevant documents according to the regulations. 
 
Article 63 The investigator shall ensure that the relevant working personnel involved in the 
trial are familiar with the principles, scope of application, product performance, operating 
methods, installation requirements and technical specifications of the investigational medical 
device, understand the pre-clinical study data and safety data of the investigational medical 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 132 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
device, and master the prevention and emergency treatment methods for possible risks in 
the clinical trial. 
 
Article 64 The investigator shall ensure that all clinical trial participants are fully aware of the 
clinical trial protocol, relevant provisions, characteristics of the investigational medical device 
and the respective responsibilities in the clinical trial, that sufficient subjects who meet the 
selection criteria in the clinical trial protocol are involved in the clinical trial and that the time 
decided in the agreement is sufficient to safely implement and complete the clinical trial in 
accordance with relevant regulations during the trial period.
 
Article 65 The investigator shall ensure that the investigational medical device is used only 
for the subjects of the clinical trial and shall not charge any fees.
 
Article 66 The investigator shall strictly follow the clinical trial protocol and shall not deviate 
from the protocol or make a substantive change of plan without the consent of the sponsor 
and the ethics committee or the approval of China Food and Drug Administration in 
accordance with the regulations. However, when immediate treatment is needed in the face 
of emergencies such as direct danger to the subjects, the written report can be provided 
afterwards. 
 
Article 67 The investigator is responsible for recruiting subjects and talking with them or the 
guardians. The investigator shall explain to the subjects the details of the investigational 
medical device and details about the clinical trial, inform the subjects of possible benefits and 
known and foreseeable risks, and obtain signed and dated informed consent forms from the 
subjects or the guardians. 
 
Article 68 The investigators or other personnel involved in the trial shall not force or induce 
subjects to participate in the trial by any improper means. 
 
Article 69 If any unexpected adverse event incurred by the investigational medical device is 
found during the clinical trial, the investigator shall modify relevant content of the informed 
consent form with the sponsor, and the affected subjects or the guardians shall re-sign the 
modified informed consent form after it is reviewed and approved by the ethics committee in 
accordance with the relevant working procedures. 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 133 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
 
Article 70 The investigator is responsible for making medical decisions related to the clinical 
trial. When any adverse event related to the clinical trial occurs, the clinical trial institution 
and the investigator shall ensure that the subjects are in a timely manner provided with 
adequate treatment and solution. When the subjects develop complications which require 
treatment, the investigator shall promptly inform the subjects of the situation.
Article 71 If any serious adverse event in the clinical trial occurs, the investigator shall 
immediately give appropriate treatment measures to the subjects, at the same time report in 
writing to the relevant medical device clinical trial management department of the clinical trial 
institution, and notify the sponsor through the department by a written notice. The medical 
device clinical trial management department shall report in writing to the corresponding 
ethics committee and the local food and drug administration department and the competent 
health and family planning department of the province, autonomous region or municipality 
where the clinical trial institution is located within 24 hours. For death events, the clinical trial 
institution and the investigator shall provide the ethics committee and the sponsor with all the 
information needed.
 
Article 72 The investigator shall record all the adverse events occurred and the device 
defects found during the clinical trial and analyze the cause of the event together with the 
sponsor, form a written analysis report, give the opinion of continuing, suspending or 
terminating the trial, and report to the ethics committee for review through the medical device 
clinical trial management department of the clinical trial institution. 
 
Article 73 The investigator shall ensure that the clinical trial data is accurately, completely, 
clearly and promptly entered in the case report form. The case report form shall be signed by 
the investigator; any change in the data shall be signed and dated by the investigator and 
meanwhile clear and identifiable original records shall be kept.
 
Article 74 The clinical trial institution and the investigator shall ensure that the data, 
documents and records formed in the clinical trial are authentic, accurate, clear and secure. 
 
Article 75 The clinical trial institution and the investigator shall be subject to the supervision 
and verification of the sponsor and supervision of the ethics committee and shall provide all 

 
Study Protocol 
A Prospective, Multi-center, Randomized Controlled 
Study to Evaluate the Safety and Efficacy of ARCR 
augmented with REGENETEN
System in Full-thickness Tears (large or massive) Repair 
versus ARCR alone
Number: 
REGENETEN.2020.01 
Version: 2.0, 08 Dec 
2021
Page: 134 of 134 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY 
 This document contains information that is confidential and proprietary to Smith+Nephew PLC and Smith+Nephew, Inc. and is 
intended for use only by Smith+Nephew and its manufacturer. It shall not be reproduced or copied in whole or in part, nor shall the 
contents be disclosed by any means without prior written permission from Smith+Nephew, nor shall anyone make any use of it that 
is contrary to the expressed or implied wishes of Smith+Nephew.  
 
TMP-CD-05-01  Clinical Protocol-Device  Revision D.1; SOP-CD-05 Clinical Protocols
required records related to the trial. The clinical trial institution and the investigator shall 
cooperate with the inspectors during the inspections assigned by the food and drug 
administration department and the competent health and family planning department. 
 
Article 76 Where the clinical trial institution and the investigator find that the risk exceeds the 
potential benefit, or the result obtained is enough to judge the safety and effectiveness of the 
investigational medical device and therefore the clinical trial needs to be suspended or 
terminated, they shall notify the subjects, ensure that the subjects are properly treated and 
followed up, and report and provide a detailed written explanation in accordance with the 
regulations. If necessary, they shall report to the local food and drug administration 
department of the province, autonomous region and municipality. 
 
When receiving a notice from the sponsor or the ethics committee to suspend or terminate 
the clinical trial, the investigator shall inform the subjects promptly and ensure that the 
subjects are properly treated and followed up. 
 
Article 77 Where the sponsor violates relevant regulations or requires the change of the trial 
data and conclusions, the clinical trial institution and the investigator shall report to the local 
food and drug administration departments of the province, autonomous region and 
municipality or China Food and Drug Administration.
 
Article 78 Upon the completion of the clinical trial, the investigator shall ensure that the 
records and reports are completed. At the same time, the investigator shall also ensure that 
the number of investigational medical devices received is consistent with that of the used, 
discarded or returned devices, and ensure that the remaining investigational medical devices 
are properly handled, recorded and documented. 
 
Article 79 The investigator may, according to the needs of the clinical trial, authorize 
corresponding personnel to recruit subjects, communicate with the subjects, record the 
clinical data and manage the investigational medical device. The investigator shall carry out 
relevant training and form the corresponding document for the personnel authorized.