A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement With JOURNEY II CR Total Knee System
Conditions: Arthroplasty, Replacement, Knee
Sponsor: Smith & Nephew, Inc.

 
 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 1 of 57   
 
 
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 Protocol 
 
 
 
 
 
 
 
Sponsor Name and Address: 
Smith & Nephew, Inc., 1450 E. Brooks Road, Memphis, TN 38116, United States  
 
 
Investigational Product(s) 
The JOURNEY II CR Total Knee System  
 
Protocol Author(s): 
Jing Xie, Clinical Senior Vice President 
 Lili Li, Associate Clinical Study Manager 
Olayinka, Babajide, Statistician 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 2 of 57   
 
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 Protocol 
1 SIGNATURES 
1.1 Principal Investigator Signature Page 
This page will be returned to Smith & Nephew Inc. and a copy retained at the investigational site. 
☐ I have read the attached protocol entitled “A Prospective Multi-Centre Study in Patients Undergoing Total Knee 
Replacement with JOURNEY II CR Total Knee System”, version <2.0>, dated <02/Jun/2021>, and agree to abide by all 
provisions set forth herein. 
I agree to comply with the Investigator’s Obligations stipulated in Section 22.3 of the protocol,  
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 Inc. 
 
Name, Address, Professional Position Signature and Date / DocuSign Stamp 
 
 
 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 3 of 57   
 
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 Protocol 
1.2 Coordinating Investigator Approval 
☐ I have read the attached protocol entitled “A Prospective Multi-Centre Study in Patients Undergoing Total Knee 
Replacement with JOURNEY II CR Total Knee System”, version <2.0>, dated <02/Jun/2021>, and agree to abide by all 
provisions set forth therein. 
Name, Address, Professional Position Signature and Date / DocuSign Stamp 
 
 
 
 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 4 of 57   
 
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 Protocol 
1.3 Sponsor Approval 
Name and Title 
Signature and Date / DocuSign Stamp 
Head of Global Clinical Operations 
Racheal, Winter 
 
 
 
 
Publications Strategy & Operations, 
Director 
Kamali, Amir 
 
Head of Global Data Analytics 
Alan, Rossington 
 
Medical Affairs Representative 
Orlandini, Luca Claudio 
 
 
 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 5 of 57   
 
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 Protocol 
2 SYNOPSIS 
Title of Study: 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement with 
JOURNEY II CR Total Knee System  
Study Design: 
Study Design 
Implant 
Prospective non-randomized 
comparative (across sites) 
JOURNEY II CR TKA (resurfaced patella and 
un-resurfaced patella)  
Sites have the options of conventional, navigation or robotics TKA and also the patella 
resurface technique (inlay/onlay). Regardless of which approach/technique, the 
approach/technique in single site should be used consistently for all study subjects if all 
possible. 
Study Type: 
Prospective, Non-randomized 
Study Product:  
The JOURNEY II CR Total Knee System consists of femoral component made from 
oxidized zirconium (OXINIUM) 
Study Purpose: 
Post-market evidence generation for JOURNEY II CR Total Knee System 
Study Objective(s): 
1.Evaluate performance of JOURNEY II TKA in APAC patient populations 
2.Evaluate impact of patella resurfacing on the outcomes of JOURNEY II TKA 
Sample Size: 
Total：Up to 480 knees (JOURNEY II CR TKA) with or without Patella Resurfaced 
• 
Resurfaced Patella: up to 240 knees 
• 
Un-resurfaced Patella: up to 240 knees 
(Decision on whether to resurface patella or not will be made by investigator based on 
patient’s conditions.) 
Number of Study Sites: 
up to 15 sites 
Targeted Global Regions: 
India/China Mainland/China (Hongkong)/Singapore/Thailand/Japan 
Inclusion Criteria: 
• 
Subjects with degenerative Osteoarthritis. 
• 
Subject is planning to have TKA using JOURNEY II CR. 
• 
Subject is able and willing to provide voluntary consent to study participation. 
• 
Subject is 18-80 years old (inclusive) * 
(* For Japan, the minimum inclusion age is 20 years old.) 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 6 of 57   
 
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 Protocol 
Exclusion Criteria: 
• 
Subjects with rheumatoid arthritis/inflammatory arthritis, posttraumatic arthritis. 
• 
Previous surgeries including HTO, UKA or TKA on the subject knee.  
• 
Subject is pregnant or breast feeding or those at a child-bearing age planning to 
become pregnant during the follow up.  
• 
Subject does not meet the indication or is contraindicated for JOURNEY II CR’s IFU.  
Study Duration: 
Total – 4.5 years (1.5 years enrolment + 3 years follow-up) 
Primary Endpoint 
•OKS at 2 years 
Secondary endpoint: 
•FJS  
•OKS 
•KSS 
•Patient Expectation  
•Patient Satisfaction  
•Radiographic Assessment 
Safety Data 
•All adverse events (AEs) including intra-operative adverse events and complications 
•Device related re-intervention  
•Device Deficiencies 
Data Collection Platform 
Medidata EDC System for data collection and centralized evaluation 
Centralized Radiographic Analysis 
Study Data Collection 
Pre-op - Baseline characteristics: 
•Age, BMI, gender 
•Diagnosis 
•Comorbidities 
•Radiographic assessment 
•KSS, OKS, Patient Expectation 
Surgery/Discharge:Perioperative: 
•Surgery info – Data, Side, Implant details, patella resurfacing, Use of enabling 
technologies (e.g. Robotics/Navigation), OR time, Blood loss 
•Discharge info – Date, Discharge Destination 
Postoperative: 
•KSS, OKS, FJS, Patient Satisfaction 
•Radiographic assessment 
• All adverse events (AEs) including intra-operative adverse events and complications 
•Device related re-intervention  
•Device Deficiencies 
Data Analysis 
•Outcomes and complications data will be analysed centrally blinded. 
•Radiographs* will be collected at each site and quantitative analysis will be conducted 
centrally. 
* The data confidentiality rules will be followed in different countries. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 7 of 57   
 
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 Protocol 
STUDY SCHEDULE  
Schedule of Events1 
Pre-Operative 
-28 to 0 days 
Operation  
Day 1 
Immediate Post -
op to 6 weeks  
Post-Op 
(Day 1 to 6 
weeks+14 days) 
6 months 
Post-Op 
(± 14 days) 
1 year  
Post-Op 
(± 30 days) 
2 years  
Post-Op  
(± 60 days) 
3 years 
Post-Op 
(± 60 days) 
Informed Consent 
x 
 
 
 
 
 
 
Inclusion/Exclusion 
x 
 
 
 
 
 
 
Demographics/Medical 
History 
x 
 
 
 
 
 
 
Operative Data Collection 
 
x 
 
 
 
 
 
Discharge Data Collection 
 
 
x 
 
 
 
 
OKS2 
x 
 
 
x 
x 
x 
x 
FJS2 
 
 
 
x 
x 
x 
x 
KSS2 
x 
 
 
x 
x 
x 
x 
Patient Expectation  
x 
 
 
 
 
 
 
Patient Satisfaction 2 
 
 
 
x 
x 
x 
x 
Quantitative Radiographic 
Assessment 
x3 
 
x4 
x5 
x5 
x5 
 
Safety Assessment (AEs, 
DDs) 
 
x 
x 
x 
x 
x 
x 
End of Study/Exit 
 
x6 
x6 
x6 
x6 
x6 
x 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 8 of 57   
 
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 Protocol 
1. All the data will be collected based on knee, except inform consent, inclusion/exclusion and demographic/medical history. 
2. Patient reported outcome can be assessed and collected remotely for follow-up period. 
3. The radiographic images prior to 3 months can be accepted for pre-operative screening data due to hospital’s SoC. 
4. Radiographic assessment can be conducted at discharge if it’s the SoC of the site. 
5. Radiographic images can be retrieved from other hospital/facility under specific image acquisition protocol and send back to site for assessment. 
6. Exit form to be completed at the point of withdrawal if the study is not completed.

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 9 of 57   
 
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 Protocol 
 
3 CONTENTS  
3.1 Table of Contents 
1 SIGNATURES .................................................................................................................. 2 
1.1 Principal Investigator Signature Page ..................................................................................... 2 
1.2 Coordinating Investigator Approval ...................................................................................... 3 
1.3 Sponsor Approval .......................................................................................................... 4 
2 SYNOPSIS ...................................................................................................................... 5 
3 CONTENTS ..................................................................................................................... 9 
3.1 Table of Contents .......................................................................................................... 9 
3.2 List of Abbreviations and Definitions....................................................................................12 
4 INTRODUCTION ..............................................................................................................14 
4.1 Background ...............................................................................................................14 
4.2 Literature Summary .......................................................................................................16 
4.3 Study Purpose .............................................................................................................17 
4.4 Safety Consideration ......................................................................................................17 
5 OBJECTIVE(S) ................................................................................................................17 
6 INVESTIGATIONAL PRODUCT(S) .........................................................................................17 
6.1 Identification ..............................................................................................................17 
6.2 Product Use ...............................................................................................................18 
6.3 Packaging and Labelling .................................................................................................18 
6.4 Product Accountability Procedures ......................................................................................19 
6.5 Surgical Technique .......................................................................................................19 
6.6 Medical Procedure ........................................................................................................19 
7 SUBJECT ENROLLMENT AND WITHDRAWAL .........................................................................19 
7.1 Subject Population ........................................................................................................19 
7.2 Inclusion Criteria..........................................................................................................20 
7.3 Exclusion Criteria .........................................................................................................20 
7.4 Screening ..................................................................................................................20 
7.5 Informed Consent .........................................................................................................20 
7.6 Enrolment .................................................................................................................21 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 10 of 57   
 
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 Protocol 
7.7 Lost to Follow-up .........................................................................................................21 
7.8 Withdrawal ................................................................................................................21 
8 STUDY DESIGN ..............................................................................................................23 
8.1 Study Design ..............................................................................................................23 
8.2 Allocation and Blinding ..................................................................................................24 
8.3 Data Management.........................................................................................................25 
8.4 Study Endpoints...........................................................................................................26 
8.5 Methods Used to Minimize Bias and Maximize Validity ...............................................................26 
9 STUDY PROCEDURES .......................................................................................................27 
9.1 Visits and Examinations ..................................................................................................27 
9.2 Study Methods and Measurements .......................................................................................34 
9.3 Health Economics/Quality of Life .......................................................................................35 
10 STATISTICAL DESIGN .....................................................................................................35 
10.1 General ...................................................................................................................35 
10.2 Analysis Populations ....................................................................................................36 
10.3 Baseline Data ............................................................................................................36 
10.4 Efficacy Analysis ........................................................................................................36 
10.5 Safety Analyses ..........................................................................................................38 
10.6 Interim Analyses.........................................................................................................38 
11 SAMPLE SIZE JUSTIFICATION ...........................................................................................39 
12 ADVERSE EVENTS AND DEVICE DEFICIENCIES.....................................................................39 
12.1 Definitions ...............................................................................................................39 
12.2 AE Coding Dictionary...................................................................................................42 
12.3 Reporting procedures ....................................................................................................42 
13 FIGURE 13-1: EVALUATION AND REPORTING OF DD ..............................................................44 
13.1 Unblinding of Investigational Product ..................................................................................44 
13.2 Follow-up of Subjects with Adverse Events ...........................................................................44 
14 INVESTIGATOR OBLIGATIONS ..........................................................................................45 
15 SPONSOR AND MONITOR RESPONSIBILITIES ........................................................................45 
15.1 Contract Research Organization ........................................................................................45 
15.2 Site Qualification Visit ..................................................................................................45 
15.3 Site Initiation Visit ......................................................................................................45 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 11 of 57   
 
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 Protocol 
15.4 Interim Monitoring Visit ................................................................................................46 
15.5 Sponsor Audits and Regulatory Inspection .............................................................................46 
15.6 Close-Out Visit ..........................................................................................................46 
16 PROTOCOL DEVIATIONS .................................................................................................46 
17 PROTOCOL AMENDMENTS ..............................................................................................46 
18 CONFIDENTIALITY OF THE STUDY ....................................................................................46 
19 STATEMENTS OF COMPLIANCE ........................................................................................46 
20 END OF STUDY .............................................................................................................47 
21 PUBLICATION POLICY ....................................................................................................47 
21.1 Publication of Study Data ...............................................................................................47 
21.2 Data Sharing .............................................................................................................47 
22 REFERENCES ................................................................................................................48 
23 APPENDICES ................................................................................................................49 
23.1 Protocol Amendment ....................................................................................................49 
23.2 Instructions for Use ......................................................................................................52 
23.3 Principal Investigator Obligations ......................................................................................52 
 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 12 of 57   
 
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 Protocol 
3.2 List of Abbreviations and Definitions 
Abbreviation 
Definition 
ADE 
Adverse Device Effect(s) 
AE 
Adverse Event(s) 
AVN 
Avascular Necrosis 
BCS 
Bi-cruciate Stabilized 
CRF 
Case Report Form(s) 
CR 
Cruiciate Retaining 
CRO 
Contract Research Organization 
CV 
Curriculum Vitae 
DA 
Degenerative Arthriti 
DD 
Device Deficiency(ies) 
DFMEA 
Design Failure Mode Effects Analysis 
FAS 
Full Analysis Set Population 
FDA 
Food and Drug Administration 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
HTO 
High Tibial Osteotomy 
ICH 
International Conference on Harmonisation  
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IP 
Investigational Product  
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
ITT 
Intention to Treat population 
KSS 
Knee Society Score 
LOCF 
Last Observation Carried Forward 
NA or N/A 
Not Applicable 
N (or n) 
Total Sample Size (or subgroup sample size) 
NSAID 
Nonsteroidal Anti-inflammatory Drug 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 13 of 57   
 
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 Protocol 
OA 
Osteoarthritis  
OKS 
Oxford Knee Score 
PI 
Principal Investigator 
PMA 
Pre-Market Authorization 
PP 
Per-protocol Population 
PTA 
Post Traumatic Arthritis 
RA 
Rheumatoid arthritis 
RCT 
Randomized Controlled Trial 
ROM 
Range of Motion 
S+N 
Smith&Nephew.Inc 
SADE 
Serious Adverse Device Effect(s) 
SAE 
Serious Adverse Event(s) 
SAF 
Safety population 
SAP 
Statistical Analysis Plan 
SoC 
Standard of care 
THA 
Total Hip Arthroplasty  
TKA  
Total Knee Arthroplasty 
USADE 
Unanticipated Serious Adverse Device Effect(s) 
WOMAC 
Western Ontario and McMaster Universities Arthritis  
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 14 of 57   
 
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 Protocol 
4 INTRODUCTION 
4.1 Background 
Arthritis is a clinical syndrome of joint pain accompanied by varying degrees of functional limitation and reduced quality of 
life. Two common etiologies of arthritis are degeneration of the joint, osteoarthritis (OA), and inappropriate inflammatory 
response, rheumatoid arthritis (RA). OA is characterized by loss of cartilage, remodeling of adjacent bone, and inflammation 
in the affected joint [1, 2]. RA is a progressive inflammatory disease that eventually causes systemic joint damage and 
disability [3]. Post-traumatic arthritis is a form of osteoarthritis following an injury to a joint. Inappropriate joint 
biomechanics due to deformities is the main risk factor for OA [4]. The joint biomechanics are directly affected by the 
malalignment of the lower extremities due to anatomical deformities [5]. Varus deformity is an excessive inward angulation 
of the lower leg and results in a bowlegged appearance. It may cause an overloading and cartilage wear in the medial knee 
compartment, which could support a degeneration of the knee joint leading to OA [5]. 
Initial treatment of arthritis may include physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen 
and corticosteroids which can be taken orally or by injection.  
Avascular necrosis (AVN) has several etiologies but fundamentally results from a decrease in blood flow to the affected 
bone, leading to cellular death [7]. Studies have reported a 3.4% and 9.4% incidence of spontaneous osteonecrosis in persons 
older than 50 and 65 years of age, respectively [8]. Initial treatment of AVN may include medication, stretching, not walking 
on the affected leg.  
Complex epiphyseal fractures around the knee joint involve the distal femur or proximal end of the tibia. The management of 
these fractures especially in elderly patients is challenging [9]. 
When the damage to the joint is advanced or available conservative treatment options are exhausted, knee arthroplasty is 
considered the most effective treatment for patients with any of these indications. 
Total knee arthroplasty (TKA) is a highly successful and frequently performed surgical treatment to reduce disability caused 
by end-stage osteoarthritis and other conditions affecting articular cartilage [10, 11]. It has been widely used in the treatment 
of knee osteoarthritis. Among them, patellofemoral joint and patellar treatment have long been the focus of scholars. 
Currently, there are three methods to treat patella during TKA: conventional replacement, selective replacement and never 
replacement [12].Scholars who advocate non-replacement of patella believe that patients' own patella can provide better 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 15 of 57   
 
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 Protocol 
patella movement track which can improve the function of knee joint and avoid prosthesis related complications [13,14].After 
patella replacement, the incidence of complications such as patella fracture, osteonecrosis, and knee extensor device rupture 
will significantly increase, and there will be prosthesis loosening, rupture and other complications caused by the prosthesis 
itself. The incidence of patellofemoral article-related complications can be effectively reduced by performing patelloplasty in 
TKA to remove peripatellar osteophytosis, repair the articular surface of patella and perform peripatellar electroablation [15]. 
However, scholars who advocate patella replacement believe that patella replacement can greatly improve the motor function 
of the knee joint by reducing the pain of the knee and enhancing the quadriceps muscle strength. Moreover, compared with 
the prosthesis, although the patella of the patient can better fit to the trochlear surface of the human body and will have better 
movement track of the patella, the patellofemoral joint surface and mechanical properties of the femoral prosthesis will 
change after TKA, and the original bonding advantages will no longer exist [16,17,18]. Some scholars reported [14] that in 
the first TKA operation, the patients with good chondral surface of patella were found to have chondral surface destruction 
during the second operation. Therefore, a patellar component matching the femoral component should be used to prevent 
damage to the patellar cartilage. Now patella replacement has become an operative method that can greatly improve patient 
satisfaction during TKA [19]. However, due to the occurrence of patellar fracture, prosthesis wear and loose, patellar impact-
syndrome and other complications after patellar replacement, some scholars are more inclined to choose patellar replacement. 
Many scholars also recommend the selective replacement of patella based on patella thickness, preoperative pre-knee pain, 
patellar cartilage damage, rheumatoid arthritis, and operator's surgical experience [15]. The utilization rate of patella 
replacement in TKA varies from country to country. 
The purpose of this study is to investigate the treatment standards and concepts of patella treatment in various research 
centres and the impact of relevant treatments on postoperative outcomes of patients on JOURNEY II CR Total Knee System. 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 16 of 57   
 
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 Protocol 
4.2 Literature Summary 
A thorough analysis of the clinical literature was performed for JOURNEY II CR Total Knee Systems. 
4.2.1 JOURNEY II CR Total Knee System 
The clinical literature analysis was performed and one clinical publication was identified. involved JOURNEY II CR system 
which focused on primary TKA. 
Demographic information 
The demographic information was summarized as shown in Table 4-1.  
Table 4-1. Demographic information for JOURNEY II CR knee system from included study 
Author, Year 
JOURNEY II Components 
Male 
(%) 
Joints 
(FU) 
Avg FU, 
yrs 
(range) 
Avg Age, 
yrs 
(range) 
Chow 2017[20] 
OxZr CR Femoral 
CR Insert 
43.9% 
114 
0.5 
66.4 
 
One study which involved JOURNEY II CR system was identified. A number of 114 joints were followed for 6 months in 
order to compare sensor-assisted TKA outcomes with manual TKA outcomes. No information of diagnosis for TKA was 
reported. In this study, standard tibial inserts of the knee system were used.  Although material of the femoral component was 
not mentioned, JOURNEY II CoCr femoral component was not available during the implantation data of this study (May 2015 
through March 2016).  Therefore, the material of femoral component that implanted in this study was assumed to be OxZr. 
 
Clinical outcomes 
Table 4-2 below shows clinical outcomes for JOURNEY II CR system from included study. 
Table 4-2. Clinical outcome information for JOURNEY II CR knee system from included study 
Author, Year 
OKS 
KSS 
(pain) 
KSS 
(function) 
KSS 
(total) 
ROM 
Pre-op 
Post-op 
Pre-op 
Post-op 
Pre-op 
Post-op 
Pre-op 
Post-op 
Pre-op 
Post-op 
Chow 2017[20] 
(sensor-assisted TKA) 
- 
(+17) 
- 
36 
- 
27 
- 
63 
105.4° 
- 
Chow 2017[20] 
(manual TKA) 
- 
(+13) 
- 
29 
- 
23 
- 
52 
109.3° 
- 
 
Chow et al compared sensor-assisted TKA outcomes with manual TKA outcomes, both with JOURNEY II CR system 
implanted.  Results at 6 months follow-up showed that patient-reported clinical outcomes were slightly higher in the sensor-
assisted TKA group than in the manual TKA group. 
 
Survivorship and Adverse events 
The study by Chow et al. that involved JOURNEY II CR system did not report any survival or revision information.  Reported 
postoperative complications included pain control issues, bleeding issues, nausea, kidney function issues, cardiac issues, 
reactive leukocytosis, dyskinesia, and transient hypotension. None of the postoperative complications were related to knee 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 17 of 57   
 
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 Protocol 
instability or unanticipated limits in range of motion. 
 
All found adverse events, where relevant, are covered under DFMEAs of JOURNEY II CR system.  
The literature review demonstrated that the JOURNEY II CR Knee System provides acceptable clinical performance with 
few complications reported. The reviewed literature did not identify additional risks beyond those previously identified in the 
DFMEA. 
4.3 Study Purpose 
This is a post-market study, and the purpose is for evidence generation for JOURNEY II CR Total Knee System 
4.4 Safety Consideration 
The contraindications, potential adverse events, precautions and warnings of JOURNEY II CR can be found in Instructions 
for Use (IFU). 
5 OBJECTIVE(S) 
The objectives of the study are listed as below, 
1. 
Evaluate performance of JOURNEY II TKA in APAC patient populations 
2. 
Evaluate impact of patella resurfacing on the outcomes of JOURNEY II TKA 
6 INVESTIGATIONAL PRODUCT(S)  
6.1 Identification 
6.1.1  Investigational Product 
The JOURNEY II CR belongs to JOURNEY II Total Knee Systems, and manufactured by Smith & Nephew, Inc. It is 
intended to be used in total knee arthroplasty surgery. 
The design philosophy behind development of the JOURNEY II CR Total Knee System is to provide the ability for greater 
flexion (155°) to those patients who have the anatomical capability to allow a greater flexion range. The JOURNEY II CR 
components are designed to work with a functional posterior cruciate ligament (PCL). 
The JOURNEY II CR Total Knee System components include: 
 
•JOURNEY II CR Femoral Components which are available in right and left designs in Oxinium material in sizes 1-10 
or CoCr material in sizes 1-9. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
 
•JOURNEY II CR Articular Inserts which are available in sizes 1-2, 3-4, 5-6, and 7-8 in right and left designs, and 
offered in 9-18 mm thicknesses and manufactured from cross-linked polyethylene (XLPE) material. 
 
•JOURNEY II Deep Dished Inserts, cruciate substituting (deep dished) articular inserts, which are available in sizes 1-2, 
3-4, 5-6, and 7-8 in right and left designs with 9-21mm thicknesses and manufactured from cross-linked polyethylene 
(XLPE) material. 
JOURNEY II Knee components are supplied sterile for single use only. Components do not incorporate medicinal 
substances, tissues, or blood products, nor is it present in the manufacturing process.  
JOURNEY II CR total knee system was first approved by FDA in 2012.  
The JOURNEY II CR Total Knee System consists of femoral component made from oxidized zirconium (OXINIUM) will be 
used for this study.  
 
Figure 6-1. JOURNEY II CR Total Knee System (OXINIUM) 
6.2 Product Use 
Please refer to IFU of the JOURNEY II CR Total Knee System for full instructions.  
6.3 Packaging and Labelling 
Packaging and labeling will be prepared to meet regulatory requirements. Package integrity and labelling should be verified 
prior to use of the product and confirmed in the eCRF. 
6.3.1 Labelling  
JOURNEY II CR Total Knee System (Oxinium) is commercial product for sites in India, China mainland, China (Hong 
Kong), Singapore, Thailand and Japan. Packaging and labelling will be prepared  per the standard commercial packaging and 
local regulatory requirements.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 19 of 57   
 
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 Protocol 
6.4 Product Accountability Procedures 
This study is a post-market study but OXINIUM Femoral component is supplied by the Sponsor in China sites and 
accountability procedure should be followed in China sites.   
China investigational sites will maintain an inventory of the IP/Ancillary Products and Study Supplies.  
The Sponsor or its designee will provide a log(s) to facilitate IP/Ancillary Products and Study Supplies inventory control. All 
IP/Ancillary Products and Study Supplies 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. 
The Study Monitor will ensure that the procedures and records are in place for the appropriate reconciliation of all 
IP/Ancillary Products and Study Supplies. As part of monitoring, the Study Monitor will check that site personnel are 
following the proper procedures for accountability and completing all necessary documentation. 
Only the product components provide by sponsor need to follow the accountability procedure, for the components purchased 
by investigational site, no product accountability procedure will be applied. 
6.5 Surgical Technique 
All study related procedures with the JOURNEY II CR Total Knee System must be performed according to the surgical 
technique and IFU of the specific Smith+Nephew Implant System. 
Surgeons selected to participate in this study will be familiar with the JOURNEY II CR Total Knee System and have written 
evidence of training and expertise in the study procedure. Pre-study cases shall be performed until the surgeon feels 
comfortable with the system in order to prevent any learning curve during the study. The number of pre-study cases depends 
on the level of the individual experience of the surgeon.  
6.6 Medical Procedure 
All surgical related procedures with the JOURNEY II CR Total Knee System must be performed according to the surgical 
technique and IFU of the specific Smith+Nephew Implant System. 
7 SUBJECT ENROLLMENT AND WITHDRAWAL 
7.1 Subject Population 
A total of up to 480 knees’ information will be collected in up to 15 sites in India, China mainland, Hong Kong, Singapore, 
Thailand and Japan There will be up to 240 knees for resurfaced patella group and up to 240 knees for un-resurfaced patella 
group. 
Group 
# of sites 
Resurfaced Patella 
Un-resurfaced Patella  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 20 of 57   
 
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 Protocol 
Up to 480 knees (JOURNEY II CR 
TKA) 
Up to 15 
Up to 240 knees 
Up to 240 knees 
7.2 Inclusion Criteria 
Subjects will be considered qualified for enrollment if they meet the following criteria: 
1. 
Subjects with degenerative Osteoarthritis. 
2. 
Subject is planning to have TKA using JOURNEY II CR. 
3. 
Subject is able and willing to provide voluntary consent to study participation. 
4. 
Subject is 18-80 years old (inclusive).* 
* For Japan, the minimum inclusion age is 20 years old. 
7.3 Exclusion Criteria 
Any one (1) of the following criteria will disqualify a potential subject from participation in the study: 
1. 
Subjects with rheumatoid arthritis/inflammatory arthritis, posttraumatic arthritis 
2. 
Previous surgeries including HTO, UKA or TKA on the subject knee 
3.  
Subject is pregnant or breast feeding or those at a child-bearing age planning to become pregnant during the follow 
up.  
4. 
Subject does not meet the indication or is contraindicated for JOURNEY II CR’s IFU. 
 
7.4 Screening 
Participating study sites are required to document all screened subjects considered for inclusion in this study. If a subject is 
excluded from the study, the reasons for exclusion will be documented in the subject's source documents and noted on the 
Screening and Enrollment Log.   
7.5 Informed Consent 
Before conducting any study procedures or examinations, the purpose and nature of the study should be explained to the 
subject in their native language.  
The subject, or their legally authorized representative, will then read, sign, and personally date the IRB/IEC-approved 
informed consent document(s) (see below for difficulties with reading and writing). Additionally, the individual who obtains 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 21 of 57   
 
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 Protocol 
consent from the subject will sign and date the informed consent document. A copy of the signed informed consent document 
will be provided to the subject, a copy will be placed in the subject’s medical record, with the original filed in the ISF. 
If the subject is unable to read, the informed consent document and associated study information may be read aloud to the 
subject in the presence of an impartial witness. If possible, the subject shall sign and personally date the Informed Consent 
Form (ICF). Where this is not possible, due to difficulties in writing, the subject shall provide verbal consent to participate in 
the study. The witness shall then personally sign and date the informed consent form, attesting that the information was 
accurately explained and that the informed consent was freely given. 
 
7.6 Enrolment 
Subjects for whom the consent process has been completed and have been treated with the study product are considered 
enrolled. 
Subjects that provided informed consent but do not receive the study treatment for any reason will be considered as screen 
failure. 
7.7  Lost to Follow-up 
A subject will be considered lost to follow-up if he/she does not appear for the scheduled study visit for 2 consecutive visits, 
and study personnel are unable to contact the subject. 
Some actively enrolled subjects will not return for follow-up exams on time. Study personnel must make a reasonable effort 
to contact the subject and document the following contact attempts before declaring a subject to be lost to follow-up: the 
subject has been contacted according to the site's policies, but no fewer than two documented phone contacts and one 
certified letter without response. Copies of all attempts to reach the subjects by 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. 
7.8 Withdrawal 
7.8.1 Withdrawal from Treatment 
Subjects may be withdrawn early from study treatment for the following reasons: 
• 
At the discretion of the Investigator due to: 
o A change in treatment is clinically warranted 
o An adverse event 
o Any other significant reason identified by the Investigator 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 22 of 57   
 
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 Protocol 
7.8.2 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 
• 
The Investigator or the Sponsor stops the study for any reason and decides to withdraw subject(s) from the study 
• 
Concurrent illness 
• 
Adverse Events/Adverse Device Effects 
• 
Any other significant reason identified by the Investigator 
For each case, information will be obtained in the source document and the Case Report Form (CRF), detailing circumstances 
leading to the withdrawal.  
Subjects who drop out or are withdrawn will not be re-entered into the study at a later date.  
If at any point during the study, the prosthesis needs to be revised for any reason the following will apply: Subjects shall 
continue to have follow-up visits in order to monitor the subject’s health status. Potential data following the revision surgery 
will not be included as study data but presented separately as safety data.  
For minor revisions, where not the whole knee implant system is replaced (e.g. replacement of inserts) the subject shall 
continue with the study specific schedule and data will be presented. 
7.8.3 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 reason(s), while 
fully respecting the subject’s privacy. The reason for withdrawal will be recorded in the CRF and source documents. 
7.8.4 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.  
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 23 of 57   
 
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 Protocol 
8 STUDY DESIGN 
8.1 Study Design 
This study is a prospective, non-randomized multi-centre study to evaluate the performance of JOURNEY II CR Total Knee 
System in APAC patient populations, also to evaluate impact of patella resurfacing on the outcomes of JOURNEY II TKA. 
Totally up to 15 sites will participate within India, China mainland, Hongkong, Singapore, Thailand and Japan. Totally up to 
480 knees information will be collected. The details can be seen in below Table 8-1. 
The decision on whether to resurface patella or not will be made by investigator based on patient’s conditions.  
Table 8-1: Overview of Study Design 
Study Design 
Implant 
Total 
Sample Size 
Number of sites 
Resurfaced Patella Un-resurfaced 
Patella  
Prospective non-
randomized comparative 
(across sites) 
JOURNEY II 
CR TKA  
Up to 480 
knees  
Up to 15 
Up to 240 knees 
Up to 240 knees 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 24 of 57   
 
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 Protocol 
Figure 8-1: Study Recruitment Timeline 
 
 
The study is expected to enroll all subjects within a 18 month timeframe. Subjects will be followed-up for a time period of 36 
months after surgery. Figure 8-1 details the Study Recruitment timeline. For the study flowchart, please see below Figure 8-2. 
 
This study is being conducted in parallel to another study (which is under same umbrella) titled: “A Prospective Multi-Centre 
Study in Patients undergoing Total Knee Replacement with Journey II BCS and CR Total Knee System” (Protocol ID: 
Journey II CR + BCS.2020.12). The study data may be combined for analysis. Further details are described in Statistical 
Design and the Statistical Analysis Plan (SAP).  
 
Figure 8-2: Study Flowchart 
 
 
 
8.2 Allocation and Blinding 
8.2.1 Treatment Allocation 
There’s no randomization for this study. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
8.2.2 Blinding 
To minimize the impact of bias associated with treatment assignment during the study, since the surgeon cannot be blinded to 
the identity of the surgical product, it is planned to appoint independent evaluators for the study, who will be blinded and 
responsible for completing study related outcome & complication upon central analysis. 
8.3 Data Management 
This study utilizes a validated, electronic data capture system. Access to the electronic data capture system is controlled 
through Smith and Nephew procedures. 
8.3.1 Data Review and Quality Assurance 
Data will be transcribed from the data source to an electronic Case Report Form (eCRF). All data requested on the eCRFs are 
considered required. Data points not collected and/or recorded will be considered deviations unless otherwise specified.  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the Principal Investigator. The 
Principal Investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
The Principal Investigator must provide his/her electronic signature on the appropriate eCRFs to be documented in 
compliance with local regulations. Changes to data previously submitted to the sponsor will require a new signature by the 
Investigator to acknowledge/approve the changes.  
Visual and computer data review will be performed in line with Smith and Nephew procedures to identify possible data 
discrepancies. Manual and automatic queries will be created within the electronic data capture system, and will be issued by 
Smith and Nephew to the site for appropriate response. Site staff are responsible for resolving all queries in the electronic 
data capture system. 
8.3.2 Retention Period 
All eCRFs will be archived once the study is completed and will kept for a period of no less than five years after the later of 
the following dates: the date of which the study is terminated or completed or; the date that the records are no longer required 
supporting marketing applications. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
8.4 Study Endpoints 
8.4.1 Primary Endpoint 
The primary endpoint for the study is defined as the OKS at 2 years. 
8.4.2 Secondary Endpoint 
The following secondary endpoints have been defined for this study as below,  
• 
OKS 
• 
FJS  
• 
KSS 
• 
Patient Expectation  
• 
Patient Satisfaction 
• 
Radiographic Assessment  
8.5 Methods Used to Minimize Bias and Maximize Validity 
8.5.1 Multiple sites 
In order to eliminate selection bias, investigators will continuously screen eligible subjects. After fulfillment of all eligibility 
criteria (including informed consent), subjects will be enrolled at multiple sites, utilizing up to 15 sites in total for the study. 
Subject enrollment will continue until the completion of recruitment of up to 480 subjects. File records and enrollment 
registration forms for screening work must be retained and submitted to the Sponsor as needed. 
8.5.2 Prospective Consecutive Enrolment 
Subjects meeting all inclusion/exclusion criteria will be allocated to receive JOURNEY II CR TKA with resurfaced patella or 
un-resurfaced patella in a 1:1 allocation ratio. The decision on whether to resurface patella or not will be made by investigator 
based on patient’s conditions.  
8.5.3 Subject Attrition  
Subject attrition for the sample size has been accounted for in the sample size estimation. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
8.5.4 Pre-specification of Statistical Analysis 
The key outcome measure has been pre-specified as well as the type of statistical analysis to be performed in order to evaluate 
this outcome. The details of the analysis will further be pre-specified in the Statistical Analysis Plan (SAP) so to minimize any 
threats to validity and yield clinically relevant estimates of effects and precision. 
9 STUDY PROCEDURES 
9.1 Visits and Examinations 
9.1.1 Summary 
For a summary of the required procedures by visit, refer to the Study Schematic Table 9-1: Study Procedures by Visit.

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 28 of 57   
 
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 Protocol 
Table 9-1: Study Procedures by Visit 
Schedule of Events1 
Pre-Operative 
-28 to 0 days 
Operation  
 (Day 1) 
Immediate Post-
op to 6 weeks  
Post-Op 
(Day 1 to 6 
weeks+14 days) 
6 months 
Post-Op 
(± 14 days) 
1 year  
Post-Op 
(± 30 days) 
2 years  
Post-Op  
(± 60 days) 
3 years 
Post-Op 
(± 60 days) 
Informed Consent 
x 
 
 
 
 
 
 
Inclusion/Exclusion 
x 
 
 
 
 
 
 
Demographics/Medical 
History 
x 
 
 
 
 
 
 
Operative Data Collection 
 
x 
 
 
 
 
 
Discharge Data Collection 
 
 
x 
 
 
 
 
OKS2 
x 
 
 
x 
x 
x 
x 
FJS2 
 
 
 
x 
x 
x 
x 
KSS2 
x 
 
 
x 
x 
x 
x 
Patient Expectation  
x 
 
 
 
 
 
 
Patient Satisfaction 2 
 
 
 
x 
x 
x 
x 
Quantitative Radiographic 
Assessment 
x3 
 
x4 
x5 
x5 
x5 
 
Safety 
Assessment 
(AEs, DDs) 
 
x 
x 
x 
x 
x 
x 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
End of Study/Exit 
 
x6 
x6 
x6 
x6 
x6 
x 
1. All the data will be collected based on knee, except inform consent, inclusion/exclusion and demographic/medical history. 
2. Patient reported outcome can be assessed and collected remotely for follow-up period. 
3. The radiographic images prior to 3 months can be accepted for pre-operative screening data due to hospital’s SoC. 
4. Radiographic assessment can be conducted at discharge if it’s the SoC of the site. 
5. Radiographic images can be retrieved from other hospital/facility under specific image acquisition protocol and send back to site for assessment. 
6. Exit form to be completed at the point of withdrawal if the study is not completed.

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
9.1.2 Screening/Pre-operative Visit (-28 to 0 days) 
1. 
Obtain written informed consent from the subject as detailed in Section 7.5 
----- Do not proceed until consent has been obtained ----- 
2. 
Obtain demographic information and medical history.  
3. 
Screen the subject for protocol inclusion/exclusion criteria. 
4. 
The eCRF will assign the subject a study number. The subject identification log shall be completed accordingly. 
5. 
Instruct the subject on treatment procedures. 
6. 
Collect radiographic assessment information. 
7. 
Collect the Patient Expectation. 
8. 
Collect the KSS score objective measures (joint alignment, instability, motions & symptoms). 
9. 
Have the subject complete the KSS score subject questions. 
10. 
Have the subject complete the OKS patient-reported outcome measure. 
11. 
Subjects will be instructed to return for the Operation Visit on a scheduled date. 
9.1.3 Operation Visit (Day 1) 
1. 
Check if there is any change in eligibility of the subject since the pre-operative visit. If the subject is no longer 
eligible, document as screening failure. 
2. 
The subject will be assigned to treatment group by investigator. 
3. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
4. 
Perform surgery and collect intra-operative data on the appropriate eCRF. 
5. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
6. 
Instruct the subject on proper postoperative care/procedures. 
7. 
Instruct the subject returning to the site for the next follow up visit on immediate post-op to 6 weeks. 
9.1.4 Immediate Post-op to 6 weeks (Day 1 to 6 Weeks+14 days)  
1. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
2. 
Collect discharge information and complete discharge eCRF. 
3. 
Collect the radiographic assessment if it’s the SoC of the hospital. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
4. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
5. 
Instruct the subject on follow-up procedures, including returning to the site for the next follow-up visit in 6 months 
(185 ± 14 days) after the surgery date. 
9.1.5 6 months (6 months ± 14 days) after surgery 
1. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
2. 
Collect the KSS score objective measures (joint alignment, instability, motions & symptoms). 
3. 
Have the subject complete the KSS score subject questions. 
4. 
Have the subject complete the OKS patient-reported outcome measure 
5. 
Collect the Patient Satisfaction information. 
6. 
Have the subject complete the FJS patient-reported outcome measure. 
7. 
Collect the radiographic assessment information.  
8. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
9. 
Instruct the subject on follow-up procedures, including returning to the site for the next follow-up visit in 1 year (365 
± 30 days) after the surgery date. 
9.1.6 1 year (1 year ± 30 days) after surgery 
1. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
2. 
Collect the KSS score objective measures (joint alignment, instability, motions & symptoms). 
3. 
Have the subject complete the KSS score subject questions. 
4. 
Have the subject complete the OKS patient-reported outcome measure 
5. 
Collect the Patient Satisfaction information. 
6. 
Have the subject complete the FJS patient-reported outcome measure. 
7. 
Collect the radiographic assessment information.  
8. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
9. 
Instruct the subject on follow-up procedures, including returning to the site for the next follow-up visit in 2 years 
(730 ± 60 days) after the surgery date. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
9.1.7 2 years (2 years ± 60 days) after surgery 
1. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
2. 
Collect the KSS score objective measures (joint alignment, instability, motions & symptoms). 
3. 
Have the subject complete the KSS score subject questions. 
4. 
Have the subject complete the OKS patient-reported outcome measure 
5. 
Collect the Patient Satisfaction information. 
6. 
Have the subject complete the FJS patient-reported outcome measure. 
7. 
Collect the radiographic assessment information.  
8. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
9. 
Instruct the subject on follow-up procedures, including returning to the site for the next follow-up visit in 3 years 
(1095 ± 60 days) after the surgery date. 
9.1.8 Exit visit 3 years (3 years ± 60 days) after surgery 
1. 
Query subject regarding any changes in general health and the use of concomitant medications/therapies. 
2. 
Have the subject complete the OKS patient-reported outcome measure 
3. 
Collect the Patient Satisfaction information. 
4. 
Have the subject complete the FJS patient-reported outcome measure. 
5. 
Collect the KSS score objective measures (joint alignment, instability, motions & symptoms). 
6. 
Have the subject complete the KSS score subject questions. 
7. 
If any adverse device effects or device deficiencies are observed or reported, they must be recorded as instructed in 
Section 12 adverse events and device deficiencies. 
8. 
Complete Exit Visit eCRF. 
9.1.9 Unscheduled Visits 
All information obtained during an unscheduled visit should be recorded in the source documents and on the appropriate 
CRF. 
9.1.10 Concomitant Medications and Therapies 
Concomitant medications and concomitant therapies (e.g., physical therapy, pain medication) are recorded at any time from 
enrollment into the study through the subject’s last study visit.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
Concomitant Medications 
Excluded Concomitant Medications 
There are no restrictions on concomitant medications for this study. 
Recording Concomitant Medications in CRF 
Medications related to the study treatment and medications used to treat an adverse event will be recorded in the eCRF. 
Reference the eCRF Completion Guidelines for how medications are recorded.  
Concomitant Therapies 
Therapies Prohibited During the Study 
There are no restrictions on concomitant therapies for this study. 
Recording Concomitant Therapies in the CRF 
Therapies related to the study treatment and therapies used to treat an adverse event will be recorded in the eCRF. Reference 
the eCRF Completion Guidelines for how therapies are recorded. 
9.1.11 Discontinued Subjects 
Discontinued subjects are those who voluntarily discontinue participation, who are withdrawn for reasons of safety or use of 
prohibited concomitant medication/therapies, who are lost to follow-up, refer to section 7.8 for further details. 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 (see Section 7.8.3). 
Finally, if appropriate, the Investigator will also advise the subject of subsequent therapy and/or procedures necessary for 
their medical condition. 
9.1.12 Subject Pregnancy 
Pregnant or breast-feeding women or women at a child-bearing age planning to become pregnant during the follow up are 
excluded from the study. Also, if a woman becomes pregnant during the study, S+N must be contacted immediately once the 
investigator is made aware of the pregnancy. All study procedures that are contraindicated during pregnancy and/or lactation 
(e.g., x-rays) will not be required. A decision will be made regarding the continuation in the study of the pregnant woman. 
Pregnancy is not an adverse event; however, complications related to the pregnancy may be reportable as determined on a 
case-by-case basis. Pregnancy-related information will be collected until the end of the pregnancy. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
9.2 Study Methods and Measurements 
9.2.1 Standard Radiographic Evaluation 
Standard radiographic evaluation on antero-posterior (A/P) and lateral views shall be performed at the determined time point 
before and after surgery in order to identify any radiographic observations such as radiolucent lines around the implant 
components. The presence of radiolucent lines, osteolysis & implant migration shall be recorded in the eCRF. 
9.2.2 Oxford Knee Score (OKS) 
The Oxford Knee Score (OKS) is a Patient Reported Outcome questionnaire that was developed to specifically assess the 
patient's perspective of outcome following Total Knee Arthroplasty. The OKS is a patient self-completion PRO containing 12 
equally weighted questions on activities of daily living. The OKS has been developed and validated specifically to assess 
perceived function and pain answered on a Likert scale after TKA. Responses to each question ranges from 0-4 with a range of 
a possible overall score from 0-48. A score of 0 is the worst possible outcome while a score of 48 is the best possible outcome. 
The benefit to this questionnaire is that it is short, practical, reliable, valid and sensitive to clinically important changes over 
time.  
A paper questionnaire will be provided by the Sponsor to be completed by the subject. Responses for the OKS will then be 
recorded in the eCRF. 
9.2.3 Forgotten Joint Score (FJS) 
The FJS comprises measures for the assessment of joint-specific patient reported outcomes. This questionnaire focuses on the 
study subject’s awareness of the partially or fully replaced knee joint in everyday life. Joint awareness can be simply defined 
as any unintended perception of a joint [49]. Subjects are asked to rate their awareness of their knee arthroplasty in 12 
questions with a five-point Likert response format: “Never”, “almost never”, “seldom”, “sometimes” and “mostly”. The item 
scores are summed and linearly transformed in a 0 to 100 scale with a high value reflecting the ability of the subject to forget 
about the replaced knee joint during the activities of daily living.  
A paper questionnaire will be provided by the Sponsor to be completed by the subject. Responses for the FJS will then be 
recorded in the eCRF. 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
9.2.4 Knee Society Score (KSS) 
The KSS is a validated tool that combines an objective physician-derived component with a subjective subject-derived 
component. The Objective Knee Score is rated by the clinician and assesses a range of clinical outcomes: UKA alignment, 
stability, ROM and symptoms. The Subject Satisfaction Score assesses the satisfaction with 5 daily activities (sitting, lying in 
bed, getting out of bed, light household duties, and leisure activities). The Subject Expectation Score evaluates the subject’s 
expectations prior to surgery. The post-operative questions differ from the pre-operative questions and ask if the subject’s 
pre-operative expectations have been met. As the pre- and post-operative scores are based on different questions, they cannot 
be directly compared. The Functional Knee Score is derived from assessments of walking and standing, standard activities, 
advanced activities, and discretionary activities. 
A paper questionnaire will be provided by the Sponsor to be completed by the subject. Responses for KSS will then be recorded 
in the eCRF. 
9.3 Health Economics/Quality of Life 
Not Applicable. 
10 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 
S+N’s Global Biostatistics group will conduct the statistical analysis for this study. Unless otherwise stated, all significance 
tests and hypothesis testing will be two-sided, performed at the 5% significance level. Resulting p-values will be quoted and 
95% two-sided confidence intervals will be generated where appropriate. Where data summaries are specified, categorical 
and ordinal variables will be summarized with frequencies and percentages. Continuous variables will be summarized with 
the following summary statistics: the number of observations, mean, median, standard deviation, minimum and maximum 
values.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 36 of 57   
 
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 Protocol 
Different statististical test will be performed based on the different data type. For continuous variables, if normality can not 
be assumed, a commensurate non-parametric test would be used. All analyses will be performed using SAS version 9.3 (or a 
later version). 
10.2 Analysis Populations 
The following are the analysis populations: 
• 
Safety Population (SAF): This is defined as all subjects who were enrolled and treated with the study devices. 
• 
Intent-to-Treat Population (ITT): The ITT population is defined as subjects from SAF, who have at least one post-
operative assessment on any of the effectiveness endpoints. 
• 
Per-Protocol Population (PP): The PP population is a subset of subjects in the ITT population, who do not have major 
protocol deviations and who satisfied all enrolment eligibility criteria. All major protocol deviations will be formally 
classified on a case-by-case basis prior to the final study database lock. 
10.3 Baseline Data 
All observations available prior to the operative date will be defined as baseline (or preoperative) data. All demographic and 
pre-operative characteristics data will be summarized at baseline. All demographic and baseline characteristics will be 
summarized using the SAF, ITT and PP analysis populations.  
10.4 Efficacy Analysis 
10.4.1 Analysis of Primary Endpoints 
The primary endpoint of this study is the OKS at 2 years. If we assume the mean of OKS at 2 years for the subjects with 
implant JOURNEY II TKA with and without Patella Resurfaced as µ1 and µ2. The hypothesis test will be as following:     
H0: µ1 = µ2 vs  
H1: µ1≠ µ2   
The mean difference (µ1-µ2) and 95% CI will be estimated. If zero is included in 95% CI of mean difference, then null 
hypothesis will be accepted, which means patella resurfacing has no impact on the outcomes of JOURNEY II TKA. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
Otherwise if zero is not included in 95% CI of mean difference, then alternative hypothesis (H1) will be accepted, which 
means patella resurfacing has significant impact on the outcomes of JOURNEY II TKA. If the lower limit of 95% CI is 
greater than 0, which means that the subject implant with Patella Resurfaced has higher OKS at 2 years. If the upper limit of 
95% CI is less than 0, which means that the subject implant with Patella Resurfaced has lower OKS at 2 years.  
In addition, the mean and 95% CI of OKS at 2 years for subjects implant with and without Patella Resurfaced will be 
estimated separately. 
The primary endpoint will be summarized using the Per-Protocol (PP) population as the primary analysis population and then 
subsequently with the ITT population for sensitivity analysis. 
10.4.2 Analysis of Secondary Endpoints 
Knee Society Score (KSS), Oxford Knee Score (OKS) and Forgotten Joint Score (FJS) 
The KSS score, OKS score and FJS score will be summarized at the pre-operative and postoperative visits and stratified by 
surgical method (resurfaced/un-resurfaced) using continuous summary characteristics. For each of these scores, repeated 
measures Analysis of Covariance (ANCOVA) models will be used to model the change from preoperative to postoperative 
and surgical method (resurfaced/ un-resurfaced patella). As a minimum, each model will contain a time points (pre-operative 
and postoperative), the investigational site and surgical method as fixed terms, subject as a random term. Pre-operative 
prognostic and demographic variables such as age, BMI, sex and other related factors will be introduced as covariates. These 
covariates will be added to the model using a stepwise approach and a covariate is retained in the final model if and only if its 
associated p-value ≤ 0.1. Model based means (adjusted means or Least Square Means), mean difference and corresponding 
standard errors associated with different time points, different surgical methods will be presented. If the p-value associated 
with the different time points and/or surgical methods in the model is significant (i.e. p < 0.05), then the 95% CIs 
corresponding to the model-based differences will additionally be presented.   
Standard Radiographic Assessment 
The presence of radiographic observations: implant loosening, implant migration, and osteolysis and other pertinent 
radiographic findings will be summarized as counts (n) and percentages (%) by visit. These would additionally be stratified 
by surgical method (resurfaced/un-resurfaced). Fisher Exact or Chi-Square test will be performed. 
Radiolucent lines (mm) by zone and visit will be summarized using descriptive statistics for continuous variables. These 
would additionally be stratified by surgical method (resurfaced/un-resurfaced). 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
Patient expectation and patient satisfaction  
The patient expectation and patient satisfaction will be summarized as counts (n) and percentages (%) by visit. These would 
additionally be stratified by surgical method (resurfaced/un-resurfaced). Fisher Exact or Chi-Square test will be performed. 
All secondary endpoints will be analyzed and summarized using the ITT and PP population. 
10.5 Safety Analyses 
All safety data will be summarized separately for different surgical methods (resurfaced/un-resurfaced) as follows: 
• 
Incidence of device-related re-interventions that occur on-study will be summarized as number (n) and percentages  
by different surgical methods and Fisher’s exact test will be performed. 
• 
Knee implant revision rate will be summarized as proportions with 95% CIs estimated using exact binomial methods 
for two surgical method separately. Proportion test will be performed to compare the revision rate from two surgical 
methods.  
All safety analysis will be performed using the SAF analysis population. 
10.6 Interim Analyses 
An interim analysis is planned after completion of the 2 years visit. More specific details on the interim analyses will be 
included in the SAP.  
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
11 SAMPLE SIZE JUSTIFICATION 
The sample size is established primarily using a precision of estimates-based approach for resurfaced and unsurfaced Patella 
cohorts separately. As a secondary concern formal statistical hypothesis testing to assess differences between the cohorts will 
be a possibility.  
Based on an underlying assumption of standard deviation of 7.4 in OKS reported in literature (Bohm et al 2012)., a minimum 
of 192 knees are required, per cohort, to ensure that there is an 80% probability that a 95% confidence interval constructed 
around the OKS score can be calculated to within ±1.2 units for each cohort of resurfaced and unresurfaced knees. To allow 
for up to 20% attrition during the data collection activity, this will be inflated to enrol a minimum of 240 knees per cohort. 
12 ADVERSE EVENTS AND DEVICE DEFICIENCIES 
12.1 Definitions 
Table 12.1-1: Categories of Adverse Event 
 
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 
(ASADE) 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
 
12.1.1 Adverse Event 
An Adverse Event (AE) is any untoward medical occurrence, unintended disease or injury or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not related to the investigational 
medical device and whether anticipated or unanticipated. 
Note 1: This definition includes events related to the investigational medical device or the comparator.  
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 use of investigational medical devices. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
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Version: 2.0, 02Jun2021 
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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 Protocol 
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. 
12.1.2 Adverse Device Effect 
An Adverse Device Effect (ADE) is an adverse event related to the use of an investigational medical device.  
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.  
Note 3: This includes "comparator" 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. 
12.1.3 Related Serious Adverse Events and Serious Adverse Device Effects 
An AE or ADE is considered a Serious Adverse Event (SAE) or Serious Adverse Device Effects (SADE) if, 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 diseases, 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) fetal distress, fetal death or a congenital abnormality or birth defect including physical or mental impairment 
Note 1: 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. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 41 of 57   
 
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 Protocol 
12.1.4 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 assessment.  
Note 1: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, severity or outcome 
has been identified in the risk assessment.   
12.1.5 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; 
Moderate - 
An event is moderate if the sign or symptom results in discomfort significant enough to cause interference 
with the subject’s usual activities; 
Severe -  An event is severe if the sign or symptom is incapacitating and results in the subject’s inability to work or engage 
in their usual activities. 
12.1.6 Device Deficiency 
A Device Deficiency (DD) is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. DD includes malfunctions, use errors and inadequate 
labeling.  
Note 1: DD includes malfunctions, use errors and inadequacy in the information supplied by the 
manufacturer including labelling.  
Note 2: This definition includes device deficiencies related to the investigational medical device or 
the comparator. 
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. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 42 of 57   
 
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 Protocol 
12.2 AE Coding Dictionary 
Coding for this study will be done per International Medical Device Regulators Forum (IMDRF) AE Terminology Annex E – 
Clinical signs, symptoms, and conditions. 
12.3 Reporting procedures 
AE of any kind and DD will be recorded in the applicable CRF and source notes to include the date of occurrence, treatment 
and the details resolution. The Investigator will evaluate all AE for relationship to the device and procedure, seriousness, and 
severity (if applicable). DD will be evaluated for potential to cause SADE.  The following timescales should be followed for 
the AE/DD information to be submitted/entered into the CRF and reported to the Sponsor or designee (see figure 12.2-1): 
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) 
All other events – according to usual timescales 
In addition to inputting SAE and SADE information within 24 hours of being aware of the event, the investigator should 
email Clinical.safety@Smith-nephew.com to alert the safety representative of the events existence and to clarify details if 
necessary. 
For ADE and DD, date of occurrence, and 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 S+N unless it is contaminated 
(e.g., used dressings must not be retained). Updates to submitted information will be recorded in the CRF 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.  
Safety reporting to the IRB/IEC and regulatory authority will be completed as per local IRB and regulatory authority 
reporting requirements and will be outlined in the study Safety Monitoring Plan (SMP).  
If there are no mandatory timelines for reporting unanticipated SADE’s and DD’s that could have led to an SADE, these will 
be reported to IEC/IRB and regulatory authorities within 10 working days 
All other events will be reported on a periodic/annual basis. 
Depending on the nature of the adverse event, S+N may request copies of the subject’s medical records, Imaging, Operative 
notes, as well as results of any relevant laboratory tests performed or other documentation related to the AE. If the subject 
was hospitalized, a copy of the discharge summary may be requested by S+N and should be forwarded as soon as it becomes 
available. In certain cases, S+N 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. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 43 of 57   
 
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 Protocol 
Figure 12.3-1: Evaluation and Reporting of AE 
Site 
aware 
of AE
Investigator 
assesses 
seriousness 
Serious
Investigator 
assesses device 
relationship
Related 
Investigator 
assesses whether 
SADE is 
anticipated
Not Related
Serious Adverse 
Event (SAE)
unanticipated
Unanticpated 
Serious Adverse 
Device Effect 
(USADE)
Anticipated 
Serious Adverse 
Device Effect 
(ASADE)
Investigator 
assesses device 
relationship
Non-serious
Related
Adverse Device 
Effect (ADE)
Not Related
Adverse Event 
(AE)
Complete CRF 
and alert S+N 
IMMEDIATELY  
Record 
information in 
patient CRF 
according to 
usual 
timescales.
Complete CRF 
and alert S+N 
without 
unreasonable 
delay. 
Record 
details in 
subject’s 
medical 
records
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 44 of 57   
 
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 Protocol 
13 FIGURE 13-1: EVALUATION AND REPORTING OF DD 
Site aware 
of DD
Investigator 
assesses whether 
could have led to 
SADE 
Potential to cause SADE
No potential to cause SADE
Complete CRF and alert S+N 
Without Unreasonable Delay
Record information in patient 
CRF according to usual 
timescales.
Record details in subject’s 
medical records
 
13.1 Unblinding of Investigational Product 
Not applicable. 
13.2 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 CRF/Clinical Study Report. 
13.2.1 Ongoing Adverse Events at Study Discontinuation 
Adverse events which are related to a study procedure or S+N IP and are ongoing at the end of subject’s 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 Investigator’s review of the event. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 45 of 57   
 
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 Protocol 
Adverse events which are not related to a study procedure or S+N IP and are ongoing at the end of subject’s 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. 
14 INVESTIGATOR OBLIGATIONS 
The Principal Investigator will comply with the commitments outlined in the Statement of Investigator, provided by the 
Sponsor, and with Good Clinical Practice (GCP), and all applicable regulatory requirements as outlined in Appendix-
Principal Investigator Obligations. 
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. 
15 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.  
15.1 Contract Research Organization  
The Sponsor may engage a Contract Research Organization (CRO) to assist in conducting this study. 
15.2 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. 
15.3 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 IRB/IEC approval.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
15.4 Interim Monitoring Visit 
Regular interim monitoring visits will be performed by the Sponsor or qualified person designated by the Sponsor. 
15.5 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. 
15.6 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 IRB/IEC reporting requirements.  When no subjects have been 
included, a remote close-out visit may be conducted.  
16 PROTOCOL DEVIATIONS 
An Investigator must not make any changes or deviate from this protocol, except to protect the life and physical well-being of 
a subject in an emergency. Protocol deviations reported by the Investigator or discovered during monitoring visits will be 
compiled in a Protocol / GCP Deviation Log (TMP-CD-31-02 Protocol/GCP Deviation Log). Significant and/or recurrent 
protocol/GCP deviations will be documented on a protocol deviation form (TMP-CD-31-01 Protocol/GCP Deviation) 
including identified root cause and, as necessary, appropriate corrective and preventive actions will be put in place and signed 
off by the study personnel. 
17 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, 
according to the applicable requirements prior to implementation at the site. 
18 CONFIDENTIALITY OF THE STUDY 
The confidentiality of this study and associated documents is governed by the terms of the Clinical Trial Agreement (CTA). 
19 STATEMENTS OF COMPLIANCE 
This clinical study will be performed in compliance with the ethical principles of the Declaration of Helsinki and ISO 14155: 
Clinical investigation of medical devices – Good Clinical Practice as far as relevant for the study type. 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
This clinical study will not commence until the required approval/favorable opinion from the IRB/IEC or regulatory authority 
has been obtained. Any additional requirements imposed by the IRB/IEC 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.  
20 END OF STUDY 
The end of this study is defined by the last follow-up visit that occurs in the whole study population. 
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. The requirement for subject follow up in 
these instances will be considered as part of these processes. 
The sponsor may decide to discontinue a specific study site under the following conditions: 
• 
Non-compliance to GCP or study protocol 
• 
Failure to enroll in subjects 
• 
Unsafe or unethical practices 
21 PUBLICATION POLICY 
21.1 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. 
21.2 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. 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. 
 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
22 REFERENCES 
1. Ferreira de Meneses, S., F. Rannou, and D.J. Hunter, Osteoarthritis guidelines: Barriers to implementation and solutions. 
Ann Phys Rehabil Med, 2016. 59(3): p. 170-173. 
2. Cutolo, M., et al., Commentary on recent therapeutic guidelines for osteoarthritis. Semin Arthritis Rheum, 2015. 44(6): p. 
611-7. 
3. Arora, S., A. Rafiq, and M. Jolly, Management of rheumatoid arthritis: Review of current guidelines. Journal of 
Arthroscopy and Joint Surgery, 2016. 3(2): p. 45-50. 
4. Saxby, D.J. and D.G. Lloyd, Osteoarthritis year in review 2016: mechanics. Osteoarthritis Cartilage, 2017. 25(2): p. 190-
198. 
5. Xie, K., et al., The effect of varus knee deformities on the ankle alignment in patients with knee osteoarthritis. J Orthop 
Surg Res, 2019. 14(1): p. 134. 
6. Cross, M., et al., The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. 
Ann Rheum Dis, 2014. 73(7): p. 1323-30. 
7. Karim, A.R., et al., Osteonecrosis of the knee. Annals of translational medicine, 2015. 3(1). 
8. Pape, D., et al., Prevalence of spontaneous osteonecrosis of the medial femoral condyle in elderly patients. Knee Surg 
Sports Traumatol Arthrosc, 2002. 10(4): p. 233-40. 
9. Parratte, S., et al., Primary total knee arthroplasty in the management of epiphyseal fracture around the knee. Orthop 
Traumatol Surg Res, 2011. 97(6 Suppl): p. S87-94. 
10. Tang, X.B., et al., A Meta-Analysis of Patellar Replacement in Total Knee Arthroplasty for Patients With Knee 
Osteoarthritis. J Arthroplasty, 2018. 33(3): p. 960-967. 
11. Winter, A.R., J.E. Collins, and J.N. Katz, The likelihood of total knee arthroplasty following arthroscopic surgery for 
osteoarthritis: a systematic review. BMC Musculoskelet Disord, 2017. 18(1): p. 408. 
12. Schindler OS. The controversy of patellar resurfacing in total knee arthroplasty: Ibisne in medio tutissimus[J]. Knee Surg 
Sports Traumatol Arthrosc，2012，7: 1227－1244. 
13. Lustig S，Magnussen RA, Dahm DL, et al. Patellofemoral arthroplasty, where are we today[J]. Knee Surg Sports 
Traumatol Arthrosc,2012,7: 1216－1226. 
14. Bourne RB，Burnett RS. The consequences of not resurfacing the patella[J]. Clin Orthop，2004，11: 166－169. 
15. Kim BS，Reitman RD, Schai PA,et al. Selective patellar nonresurfacing in total knee arthroplasty. 10 year results[J]. Clin 
Orthop,1999,10: 81－88. 
16. Wallin & Dalholm AB. Use of patellar button for TKA in 2008[R].Sweden: Annual Report 2009－The Swedish Knee 
Arthroplasty Register，2009: 16－19. 
17. Phillips AM,Goddard NJ,Tomlinson JE. Current techniques in total knee replacement: results of a national survey[J]. Ann 
R Coll Surg Engl,1996,6: 515－520. 
18. Fu Y,Wang G,Fu Q. Patellar resurfacing in total knee arthroplasty for osteoarthritis: a meta－analysis［J］. Knee Surg 
Sports Traumatol Arthrosc， 2011，9: 1460－1466. 
19. Pilling RW,Moulder E,Allgar V, et al. Patellar resurfacing in primary total knee replacement: a meta－analysis［J］. J 
Bone Joint Surg Am，2012，24: 2270－2278. 
20. Chow JC, Breslauer L. The Use of Intraoperative Sensors Significantly Increases the Patient-Reported Rate of 
Improvement in Primary Total Knee Arthroplasty. Orthopedics. 2017;40(4):e648-e651. 
 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 49 of 57   
 
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 Protocol 
23 APPENDICES 
23.1 Protocol Amendment  
23.1.1 General Purpose 
The purpose to have the 1st protocol amendment from version 1.0 into version 2.0 is to further update the section 12 about 
safety reporting process to compliance with the SOP requirements and update the section 6.2 about product accountability 
procedures for China specific requirement. 
23.1.2 Rationale 
The rationale to 1st update the protocol is due to SOP-CD-05 requirement that both AE and DD should be reported, thus update 
the section 12 to compliance with protocol SOP template TMP-CD-05-01. And as China need to free provide the Oxinium 
femoral component, the device accountability will be needed for China sites. 
23.1.3 Effect on Study Status 
Not applicable. This amendment is to be in effect and implemented prior to subject enrollment. 
23.1.4 Details 
1st Update from Version 1.0 to Version 2.0 
Section 
Current Text 
Version 1.0 (10DEC2020) 
Revised Text 
Version 2.0 (02Jun2021) 
Header 
Version: 1.0, 10DEC2020 
Version: 2.0, 02Jun2021 
Section 2-Synopsis-
Safety Data  
•Adverse events (AEs) related to 
subsequent surgical interventions on 
subject knee due to any reasons  
•AEs identified from qualitative 
radiographic assessment 
• All adverse events (AEs) including intra-operative 
adverse events and complications 
• Device related re-intervention  
• Device Deficiencies  
Section 2-Synopsis-
Study data collection-
Postoperative 
•Adverse events (AEs) related to 
subsequent surgical interventions on 
subject knee due to any reasons  
•AEs identified from qualitative 
radiographic assessment 
• All adverse events (AEs) including intra-operative 
adverse events and complications 
• Device related re-intervention  
• Device Deficiencies  
Section 2-Synopsis -
Study Schedule 
Adverse Events related to subsequent 
surgical interventions on subject knee 
due to any reasons & identified from 
qualitative radiographic assessment 
Safety Assessment (AEs, DDs) 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 50 of 57   
 
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 Protocol 
Section 6.4 
6.4 Product Accountability 
Procedures 
No product accountability procedures 
will be applied for the JOURNEY II 
Knee Implant Systems as these are 
commercially available products. 
 
This study is a post-market study but OXINIUM 
Femoral component is supplied by the Sponsor in 
China sites and accountability procedure should be 
followed in China sites.   
China investigational sites will maintain an inventory 
of the IP/Ancillary Products and Study Supplies.  
The Sponsor or its designee will provide a log(s) to 
facilitate IP/Ancillary Products and Study Supplies 
inventory control. All IP/Ancillary Products and Study 
Supplies 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. 
The Study Monitor will ensure that the procedures and 
records are in place for the appropriate reconciliation of 
all IP/Ancillary Products and Study Supplies. As part 
of monitoring, the Study Monitor will check that site 
personnel are following the proper procedures for 
accountability and completing all necessary 
documentation. 
Only the product components provide by sponsor need 
to follow the accountability procedure, for the 
components purchased by investigational site, no 
product accountability procedure will be applied. 
Section 9.1-Table 9.1 
Adverse Events related to subsequent 
surgical interventions on subject knee 
due to any reasons & identified from 
qualitative radiographic assessment 
Safety Assessment (AEs, DDs) 
Section 9.1.3- Part 5 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment. 
Collect any adverse events or DDs 
Section 9.1.4- Part 4 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment. 
Collect any adverse events or DDs 
Section 9.1.5- Part 8 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
Collect any adverse events or DDs 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
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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 Protocol 
identified from qualitative 
radiographic assessment. 
Section 9.1.6- Part 8 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment. 
Collect any adverse events or DDs 
Section 9.1.7- Part 8 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment. 
Collect any adverse events or DDs 
Section 9.1.8- Part 7 
Collect any adverse events related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment. 
Collect any adverse events or DDs 
Section 12.1.6 
N/A 
A Device Deficiency (DD) is an inadequacy of a 
medical device with respect to its identity, quality, 
durability, reliability, safety or performance. DD 
includes malfunctions, use errors and inadequate 
labeling.  
Note 1: DD includes malfunctions, use errors and 
inadequacy in the information supplied by the 
manufacturer including labelling.  
Note 2: This definition includes device deficiencies 
related to the investigational medical device or the 
comparator. 
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. 
Section 12.2 
NA 
Coding for this study will be done per International 
Medical Device Regulators Forum (IMDRF) AE 
Terminology Annex E – Clinical signs, symptoms, and 
conditions.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 52 of 57   
 
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 Protocol 
Section 12.3 
Adverse events (AEs) related to 
subsequent surgical interventions on 
subject knee due to any reasons & 
identified from qualitative 
radiographic assessment will be 
recorded in the applicable CRF and 
source notes to include the date of 
occurrence, treatment and the details 
resolution. The Investigator will 
evaluate these AE for relationship to 
the device and procedure, 
seriousness, and severity (if 
applicable). The following timescales 
should be followed for the AE 
information to be submitted/entered 
into the CRF and reported to the 
Sponsor or designee (see Figure 12-
1): 
• 
SAE – immediately (i.e. 
within 24 hours of the 
investigator being informed 
about the event) 
• 
All other events – according 
to usual timescales 
AE of any kind and DD will be recorded in the 
applicable CRF and source notes to include the date of 
occurrence, treatment and the details resolution. The 
Investigator will evaluate all AE for relationship to the 
device and procedure, seriousness, and severity (if 
applicable). DD will be evaluated for potential to cause 
SADE.  The following timescales should be followed 
for the AE/DD information to be submitted/entered into 
the CRF and reported to the Sponsor or designee (see 
figure 12.2-1): 
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) 
All other events – according to usual timescales 
 
 
23.2 Instructions for Use 
Please refer to the IFU of JOURNEY II CR Total Knee Systems. 
23.3 Principal Investigator Obligations  
Since this is a multiple-country study, overall ISO14155 will be followed, and for each country, the study should be 
compliance with local regulations and laws. 
23.3.1 ISO14155:2011 
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: 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 53 of 57   
 
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 Protocol 
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 
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 ISO 14155:2011. 
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 subject’s rights, safety, and 
well-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 
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. 
Approval of the request for deviations that can affect the subject’s rights, 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, 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 54 of 57   
 
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 Protocol 
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 requirements also apply with respect to informed consent 
obtained from a subject’s legally authorized representative:  
i. 
Ensure that the PI or his/her authorized designee conducts the informed consent process 
ii. 
Include all aspects of the clinical investigation that are relevant to the subject’s decision to participate 
throughout the clinical investigation 
iii. 
Avoid any coercion or undue improper influence on, or inducement of, the subject to participate 
iv. 
Not waive or appear to waive the subject’s legal rights 
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 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 informed consent of the subject 
is not possible because of the subject’s medical condition, the informed consent of the subject’s legally 
authorized representative, if present, shall be requested.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 55 of 57   
 
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 Protocol 
2. 
When it is not possible to obtain prior informed consent from the subject, and the subject’s legally 
authorized representative, is not available, the subject 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, as soon as 
possible, about the subject’s inclusion in the 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.  
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 subject 
(or the subject’s legally 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. 
Information on the role of Sponsor’s representative in the clinical investigation 
ix. 
Contact persons 
x. 
Statement declaring that new findings or the reasons for any amendment to the protocol that affect the 
subject’s continued participation shall be made available to the subject.  
xi. 
Statement indicating that, upon the subject’s approval, the subject’s personal physician will be informed of 
the subject’s participation 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 investigator’s instructions 
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 
v. 
An acknowledgment of the information provided and confirmation that all the subject’s questions were 
answered 
vi. 
A statement confirming that the subject or his/her legally authorized representative agrees to the use of the 
subject’s relevant personal data for the purpose of the clinical investigation 
vii. 
A statement confirming that the subject or his/her legally authorized representative agrees that Sponsor’s 
representatives, regulatory authorities and IEC representatives will be granted direct access to the subject’s 
medical records.  

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 56 of 57   
 
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 Protocol 
g. 
New information: if new information becomes available that can significantly affect a subject’s future health and 
medical care, that information shall be provided to the 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, 
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 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, 

 
Clinical Protocol - Device 
Study Number: Journey II CR.2020.11 
A Prospective Multi-Centre Study in Patients Undergoing Total Knee Replacement 
with JOURNEY II CR Total Knee System 
Version: 2.0, 02Jun2021 
Page: 57 of 57   
 
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 Protocol 
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. 
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. 
*To the extent outlined in section 12.