A Prospective, Double Blinded, Multicenter, Randomized, Controlled Trial to Evaluate Mechanical Debridement vs. Radiofrequency-Based Debridement in the Treatment of Articular Cartilage Lesions
Phase: NA
Conditions: Chondral Lesion Plus Partial Medial Meniscectomy
Sponsor: Smith & Nephew, Inc.

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 1 of 101 
Document Date: 27OCT2016; Version 4.0 
 
Protocol Name:  
A Prospective, Double Blinded, Multi-Center, Randomized, Controlled 
Trial to Evaluate Mechanical Debridement vs. Radiofrequency-Based 
Debridement in the treatment of Articular Cartilage Lesions 
 
Short Title:    
ArthroCare Cartilage Trial (ACT) 
 
Protocol Number:    SM-2012-02 
 
Protocol Version:   Version 4.0 
 
Protocol Date:            October 27, 2016 
 
Sponsor:   
 
Smith & Nephew, Inc.  
1450 E. Brooks Road  
Memphis, TN 38116  
US     
 
 
 
 
 
Nondisclosure Statement 
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 
manufacturers.  It shall not be reproduced or copied in whole or in part, nor shall the contents be 
disclosed by any mean 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.  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 2 of 101 
Document Date: 27OCT2016; Version 4.0 
Table of Contents 
1. STUDY PROTOCOL SIGNATURE PAGE ................................................................................................... 5 
2. TABLE 1:  LIST OF ABBREVIATIONS ....................................................................................................... 6 
3. TABLE 2:  STUDY SYNOPSIS .................................................................................................................... 7 
4. TABLE 3:  STUDY FLOWCHART AND FOLLOW-UP ASSESSMENTS ................................................... 9 
5. BACKGROUND INFORMATION ............................................................................................................... 10 
5.1 INTRODUCTION ....................................................................................................................................... 10 
5.2 STUDY DEVICE ....................................................................................................................................... 11 
5.3 MECHANISM OF ACTION........................................................................................................................... 12 
6. OVERVIEW OF INVESTIGATIONAL PLAN .............................................................................................. 13 
7. STUDY OBJECTIVES ................................................................................................................................ 14 
7.1 STUDY PURPOSE .................................................................................................................................... 14 
7.2 PRIMARY OBJECTIVE ............................................................................................................................... 14 
7.3 SECONDARY OBJECTIVE .......................................................................................................................... 14 
8. STUDY ENDPOINTS .................................................................................................................................. 15 
8.1 PRIMARY ENDPOINT ................................................................................................................................ 15 
8.2 SECONDARY ENDPOINTS ......................................................................................................................... 15 
9. PROTOCOL ................................................................................................................................................ 15 
9.1 STUDY DESIGN ....................................................................................................................................... 15 
9.2 SUBJECT RECRUITMENT AND SCREENING ................................................................................................ 16 
9.3 STUDY DURATION AND FOLLOW-UP ......................................................................................................... 17 
10. SELECTION OF SUBJECTS ..................................................................................................................... 17 
10.1 INCLUSION CRITERIA ............................................................................................................................. 17 
10.2 EXCLUSION CRITERIA ............................................................................................................................ 18 
10.3 EARLY WITHDRAWAL OF SUBJECTS ........................................................................................................ 20 
10.3.1 
When and How to Withdraw Subjects ................................................................................. 20 
10.3.2 
Data Collection and Follow-up for Withdrawn Subjects ...................................................... 21 
10.3.3 
Study Site Termination ........................................................................................................ 21 
10.4 PRIOR AND CONCOMITANT THERAPY ...................................................................................................... 21 
11. STUDY PROCEDURES .............................................................................................................................. 22 
11.1 STUDY INTERVENTIONS ......................................................................................................................... 22 
11.1.1 
Single Medial Femoral Chondral Lesion Treatment plus Partial Medial Meniscectomy 
Procedure ........................................................................................................................................... 22 
11.2 OUTCOME MEASURES ........................................................................................................................... 22 
11.2.1 
Subject Questionnaires ....................................................................................................... 22 
11.2.2 
Physical Assessment .......................................................................................................... 23 
11.2.3 
Magnetic Resonance Imaging (MRI)................................................................................... 23 
11.3 VISIT SUMMARY .................................................................................................................................... 23 
11.3.1 
Visit 1:  Screening/Baseline (days -21 to -1) ....................................................................... 23 
11.3.2 
Visit 2:  Surgery (Day 0) ...................................................................................................... 25 
11.3.3 
Visit 3:  Day 10 Follow-Up (+/- 3 day(s)) ............................................................................. 27 
11.3.4 
Visit 4:  Week 6 Follow-up (+/- 5 day(s)) ............................................................................. 27 
11.3.5 
Visit 5:  Week 12 Follow-Up (+/- 7 day(s)) .......................................................................... 28 
11.3.6 
Visit 6: Week 24 Follow-Up (+/- 14 day(s)) ......................................................................... 28 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 3 of 101 
Document Date: 27OCT2016; Version 4.0 
11.3.7 
Visit 7:  Week 36 Follow-Up (+/- 14 day(s)) ........................................................................ 29 
11.3.8 
Visit 8:  Week 52 Follow-Up (+/- 28 day(s)) ........................................................................ 29 
11.3.9 
Visit 9:  Week 104 Follow-Up (+/- 56 day(s)) ...................................................................... 30 
11.3.10 
Optional Follow-Up Visit, Unscheduled Visit Procedures ............................................... 31 
11.3.11 
Post-operative Rehabilitation Guideline .......................................................................... 31 
12. STATISTICAL ANALYSIS  ......................................................................................................................... 31 
12.1 TREATMENT GROUPS ............................................................................................................................ 31 
12.2 DESCRIPTION OF STUDY ENDPOINTS ...................................................................................................... 32 
12.2.1 
Primary Efficacy Endpoint ................................................................................................... 32 
12.2.2 
Secondary Endpoints: ......................................................................................................... 32 
12.2.3 
Safety Assessments ............................................................................................................ 33 
12.3 SAMPLE SIZE DETERMINATION, POWER CALCULATION, AND RATIONALE ................................................... 33 
12.4 RANDOMIZATION ................................................................................................................................... 34 
12.5 BLINDING .............................................................................................................................................. 35 
12.5.1 
Subject Blinding................................................................................................................... 35 
12.5.2 
Study MRI Blinding .............................................................................................................. 35 
12.5.3 
Interim Analysis (IA) ............................................................................................................ 35 
12.5.4 
General Statistical Considerations ...................................................................................... 37 
12.6 ANALYSIS POPULATIONS ........................................................................................................................ 38 
12.6.1 
Intent-to-Treat Population ................................................................................................... 38 
12.6.2 
Per Protocol Population ...................................................................................................... 38 
12.6.3 
Safety Population ................................................................................................................ 38 
12.7 STATISTICAL METHODS.......................................................................................................................... 38 
12.7.1 
Subject Disposition .............................................................................................................. 38 
12.7.2 
Demographic and Baseline Characteristics ........................................................................ 39 
12.7.3 
Protocol Deviations ............................................................................................................. 39 
12.7.4 
Prior and Concomitant Medications .................................................................................... 39 
12.7.5 
Efficacy Analyses ................................................................................................................ 39 
12.7.6 
Safety Analyses................................................................................................................... 40 
13. SAFETY AND ADVERSE EVENTS ........................................................................................................... 42 
13.1 DEFINITIONS ......................................................................................................................................... 42 
13.1.1 
Adverse Event ..................................................................................................................... 42 
13.1.2 
Adverse Device Effect ......................................................................................................... 42 
13.1.3 
Serious Adverse Events ...................................................................................................... 42 
13.1.4 
Unanticipated Adverse Device Effect .................................................................................. 43 
13.2 RECORDING OF ADVERSE EVENTS ......................................................................................................... 43 
13.3 REPORTING........................................................................................................................................... 44 
13.3.1 
Adverse Event Reporting Period ......................................................................................... 44 
13.3.2 
Reporting Adverse Events .................................................................................................. 44 
13.3.3 
Reporting Serious Adverse Events and Incidents ............................................................... 46 
13.3.4 
Informed Consent Violation Reporting ................................................................................ 50 
13.3.5 
Protocol Deviation Reporting .............................................................................................. 50 
13.3.6 
Progress Reports ................................................................................................................ 50 
13.3.7 
Final Report ......................................................................................................................... 50 
13.4 UNBLINDING PROCEDURES .................................................................................................................... 50 
13.5 DATA SAFETY MONITORING BOARD ........................................................................................................ 51 
13.6 STUDY STOPPING RULES ....................................................................................................................... 51 
13.7 MEDICAL MONITORING........................................................................................................................... 51 
13.8 ASSESSMENT OF RISKS AND BENEFITS ................................................................................................... 52 
13.8.1 
Risks of Procedure .............................................................................................................. 53 
13.8.2 
Risks of Study Device ......................................................................................................... 54 
13.8.3 
Benefits of Study Device ..................................................................................................... 54 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 4 of 101 
Document Date: 27OCT2016; Version 4.0 
14. DATA HANDLING AND RECORD KEEPING ........................................................................................... 54 
14.1 CONFIDENTIALITY .................................................................................................................................. 54 
14.2 SOURCE DOCUMENTS ........................................................................................................................... 55 
14.3 CASE REPORT FORMS ........................................................................................................................... 56 
14.4 DATA MANAGEMENT .............................................................................................................................. 56 
14.5 RECORDS RETENTION ........................................................................................................................... 57 
15. STUDY MONITORING, AUDITING, AND INSPECTING ........................................................................... 57 
15.1 STUDY MONITORING .............................................................................................................................. 57 
15.2 AUDITING AND INSPECTING .................................................................................................................... 58 
16. ETHICAL CONSIDERATIONS ................................................................................................................... 58 
16.1 PROTOCOL AMENDMENTS ...................................................................................................................... 59 
16.2 INFORMED CONSENT ............................................................................................................................. 59 
17. INVESTIGATOR TRAINING ....................................................................................................................... 60 
17.1 INVESTIGATOR TRAINING ....................................................................................................................... 60 
17.2 TRAINING OF STAFF ............................................................................................................................... 60 
18. PUBLICATION PLAN ................................................................................................................................. 60 
19. INSTITUTIONAL REVIEW BOARD / RESEARCH ETHICS BOARD ....................................................... 61 
20. REFERENCES ............................................................................................................................................ 63 
21. APPENDICIES ............................................................................................................................................ 64 
21.1 APPENDIX A - DRAFT INFORMED CONSENT ............................................................................................. 64 
21.1.1 
US Sites- Draft Informed Consent ....................................................................................... 64 
21.1.2 
Canadian Site- Draft Informed Consent .............................................................................. 73 
21.2 APPENDIX B – DRAFT SUBJECT QUESTIONNAIRES .................................................................................. 82 
21.2.1 
International Knee Documentation Committee (IKDC) ....................................................... 82 
21.2.2 
Visual Analog Scale (VAS), knee pain ................................................................................ 85 
21.2.3 
Knee Injury and Osteoarthritis Outcome Score (KOOS)..................................................... 87 
21.2.4 
SF-12 ................................................................................................................................... 92 
21.2.5 
EQ-5D-5L ............................................................................................................................ 96 
21.2.6 
Subject Satisfaction ........................................................................................................... 100 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 5 of 101 
Document Date: 27OCT2016; Version 4.0 
 
1. 
STUDY PROTOCOL SIGNATURE PAGE 
 
Confidentiality Statement:    
 
This Clinical Investigational Plan (CIP) contains privileged or confidential information, which is 
the property of the Sponsor. Information may not be disclosed to a third party without written 
authorization from the Sponsor. 
 
Regulatory Statement: 
 
This study will be conducted according to the protocol, the US Code of Federal Regulations 21 
CFR Part 50, 54, 56, and 812, the ethical principles of GCP as defined in ICH E6, and the ICH 
Guidelines. All aspects of this study will be conducted in accordance with all national, state, and 
local laws of the pertinent regulatory authorities.  
 
Investigator’s Statement: 
 
I understand the protocol “A Prospective, Double Blinded, Multi-Center, Randomized, 
Controlled Study to Evaluate Mechanical Debridement vs. Radiofrequency-Based Debridement 
in the treatment of Articular Cartilage Lesions.” 
 
I agree to conduct this study in accordance with the design and specific provisions of the 
protocol in this CIP and to inform all who assist me in the conduct of this study of their 
responsibilities and obligations. I agree to await Institutional Review Board (IRB)/Research 
Ethics Board (REB) approval of the CIP and Informed Consent Form (ICF) before initiating the 
study, to obtain informed consent prior to subject enrollment in the study, to collect and record 
data as required by this CIP and corresponding Case Report Forms (CRF), to prepare Annual, 
Final, and Adverse Events (AE) Reports as required, and to maintain study documentation for 
the period of time required. 
  
I agree to ensure the rights, safety, and well-being of the subjects involved in the study. 
 
Investigator’s Printed Name:  
                                       
 
 
Investigator’s Signature: 
 
Date of Signature: 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 6 of 101 
Document Date: 27OCT2016; Version 4.0 
2. 
TABLE 1:  LIST OF ABBREVIATIONS  
 
ACT 
ArthroCare Cartilage Trial 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BMI 
Body Mass Index 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CIP 
Clinical Investigation Plan 
CRA 
Clinical Research Associate 
CRO 
Clinical Research Organization 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
ICF 
Informed Consent Form 
ICRS 
International Cartilage Repair Society 
IFU 
Instructions For Use 
IKDC 
International Knee Documentation Committee 
IRB 
Institutional Review Board 
KOOS 
Knee Injury and Osteoarthritis Outcome Score 
MRI 
Magnetic Resonance Image 
RF 
Radiofrequency 
REB 
Research Ethics Board 
SAE 
Serious Adverse Event 
USADE 
Unanticipated Serious Adverse Device Effect 
VAS 
Visual Analogue Scale 
WORMS 
Whole-organ MRI Score 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 7 of 101 
Document Date: 27OCT2016; Version 4.0 
3. 
TABLE 2:  STUDY SYNOPSIS 
Title 
A Prospective, Double Blinded, Multi-Center, Randomized, Controlled 
Trial to Evaluate Mechanical Debridement vs. Radiofrequency-Based 
Debridement in the treatment of Articular Cartilage Lesions 
Short Title 
ArthroCare Cartilage Trial (ACT) 
Protocol Number 
SM-2012-02 
Study Design 
Non-Inferiority, Adaptive Study Design 
Study Duration 
2 year post-operative follow-up 
Study Center(s) 
Up to 13 clinical sites 
Number of Subjects 
82 subjects randomized 
Objectives 
Primary: 
The primary objective is to evaluate clinical outcomes following 
Radiofrequency-Based Debridement or Mechanical Debridement 
for subjects requiring treatment of a single medial femoral chondral 
lesion plus partial medial meniscectomy procedure 
 
Secondary:  
The secondary objectives are to evaluate imaging and additional 
clinical outcomes 
Study Population 
Male and non pregnant female subjects ≥ eighteen (18) years of age 
requiring a treatment of a single medial femoral chondral lesion plus 
partial medial meniscectomy procedure 
Study Intervention 
Group I:  Radiofrequency-Based Debridement: 
Quantum™ 2 Controller plus Paragon T2™ ICW  or  
WEREWOLF™ Controller plus FLOW 50™ Wand (study devices) 
Control Intervention 
Group II:  Mechanical Debridement (control device) 
Randomization 
Scheme 
Subjects will be assigned by a 1:1 schema 
Intervention 
Surgical intervention for a single medial femoral chondral lesion 
treatment plus partial medial meniscectomy procedure 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 8 of 101 
Document Date: 27OCT2016; Version 4.0 
Endpoints 
Primary Endpoint: 
 Change in Knee and Osteoarthritis Outcomes Scores (KOOS) 
scores at Week 52 post-operative compared to baseline 
Secondary Endpoints: 
 
Clinical Endpoints 
o Change in International Knee Documentation 
Committee (IKDC) Subjective Knee Evaluation Form 
scores from baseline  
o Change in International Knee Documentation 
Committee (IKDC)  Knee Examination Form scores 
from baseline  
o Change in KOOS scores from baseline at Weeks 6, 12, 
24, 36 and 104 
o Change in Visual Analogue Scale (VAS) scores from 
baseline 
o Change in SF-12 scores from baseline 
o Change in EQ-5D-5L scores from baseline 
o Subject Satisfaction at Weeks 52 and 104 
 
Imaging Endpoints 
o MRI assessments at Day 10, Weeks 52 and 104 
o ICRS grade of chondral lesion at Day 10, Weeks 52 and 
104 
 
Safety Assessments 
o Incidence of Adverse Events 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 9 of 101 
Document Date: 27OCT2016; Version 4.0 
4. 
TABLE 3:  STUDY FLOWCHART AND FOLLOW-UP ASSESSMENTS 
Procedure 
Screening/
Baseline 
Surgery   
Post-Operative Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
Informed Consent 
X1 
 
 
 
 
 
 
 
 
Medical History & 
Demographics 
X 
 
 
 
 
 
 
 
 
Subject Eligibility 
Verification  
X 
X 
 
 
 
 
 
 
 
Physical Assessment - 
Knee 
X 
 
X 
X 
X 
X 
X 
X 
X 
Magnetic Resonance 
Imaging  (MRI) 
X2 
 
X 
 
 
 
 
X 
X 
Weight bearing AP / 
Lateral / Merchant 
View 
X 
 
 
 
 
 
 
 
 
Weight-bearing 
posteroanterior 
radiograph 
X 
 
 
 
 
 
 
 
 
Standing Long Leg 
Alignment 
X 
 
 
 
 
 
 
X 
 
International Cartilage 
Repair Society 
classification (ICRS) 
 
X3 
X4 
 
 
 
 
X4 
X4 
International Knee 
Documentation 
Committee (IKDC) 5 
X 
 
 
X6 
X 
X 
X 
X 
X 
Visual Analogue Scale 
(VAS), knee pain 
X 
 
X 
X 
X 
X 
X 
X 
X 
Knee Injury and 
Osteoarthritis 
Outcome Score 
(KOOS) 
X 
 
 
X 
X 
X 
X 
X 
X 
SF-12 
X 
 
 
X 
X 
X 
X 
X 
X 
EQ-5D-5L 
X 
 
X 
X 
X 
X 
X 
X 
X 
Subject Satisfaction 
 
 
 
 
 
 
 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 10 of 101 
Document Date: 27OCT2016; Version 4.0 
  
1 Must occur prior to any study–specific procedures 
 
 
  
2 MRI must occur within 9 months of enrollment into this study confirming presence of a medial femoral chondral lesion and 
medial meniscal tear requiring a partial meniscectomy 
3 International Cartilage Repair Society (ICRS) classification will be used for intra-operative arthroscopic confirmation of the 
lesion grade 
4 International Cartilage Repair Society (ICRS) classification will be used for determination of lesion grade by MRI 
5 International Knee Documentation Committee (IKDC) Subject Knee Evaluation and Knee Examination Forms will be used 
6 IKDC Knee Examination Form - Subject dependent 
7 Post-operative Rehabilitation per Investigator standard of care 
 
 
 
5. 
BACKGROUND INFORMATION 
5.1 
Introduction 
Articular cartilage defects or chondral lesions are commonly detected during arthroscopy 
when treating knee pathology such as a torn meniscus or damaged anterior cruciate ligament 
(ACL).  Three recent large studies consisting of 190, 1,000, and 25,124 patients each showed 
that between 60% and 70% of patients having arthroscopic knee surgery have concomitant 
chondral lesions (1-3).  These lesions were found to occur most often in patients undergoing 
meniscal tear repair or anterior cruciate ligament repair and were usually found on the medial 
femoral condyle. 
 
Focal chondral lesions observed during arthroscopy are usually addressed using any one of 
several different treatment options that are selected using a clearly defined algorithm (4).  
The treatment selected depends on the severity of the lesion, which is graded using a scheme 
such as the International Cartilage Research Society (ICRS) classification system (5).  When 
chondral lesions are treated surgically, first line methods generally consist of debriding loose 
or worn articular cartilage, with the goal of stabilizing the lesion to prevent further 
degeneration.  One method of treatment includes radiofrequency (RF) -based debridement. A 
prospective study by Voloshin et al. followed one hundred ninety-three patients that 
underwent bipolar radiofrequency–based chondroplasty over 38 months.  Of these patients, 
Adverse Events  
 
X 
X 
X 
X 
X 
X 
X 
X 
Post-operative 
Rehabilitation7 
 
 
X 
X 
 
 
 
 
 
Concomitant 
Medications  
X 
 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 11 of 101 
Document Date: 27OCT2016; Version 4.0 
fifteen with a total of twenty-five defects were re-examined when undergoing repeat 
arthroscopy for recurrent or new injuries. Of the twenty-five lesions, only three demonstrated 
further deterioration of the cartilage defects after treatment with RF (6). Limited clinical data 
exists, however, evaluating the use of radiofrequency-based debridement for the treatment of 
chondral lesions compared to another commonly used treatment method, mechanical 
debridement. Owens and Busconi reported that women treated for isolated patellofemoral 
chondral lesions using a bipolar RF-based device tended to have better joint evaluation 
scores and demonstrated less incidence of crepitus at one and two years post-operatively than 
those receiving mechanical shaver-based treatment (7).  In patients undergoing partial 
meniscectomy and having concomitant medial femoral condyle chondral lesions treated 
using mechanical debridement alone or mechanical and RF-based debridement, Barber and 
colleagues observed no significant differences between treatment groups in clinical outcomes 
through one year (8).  Spahn et al. reported contrary findings to the Barber group when 
studying a similar patient cohort in Germany.  In their prospective, randomized, controlled 
trial they found significantly better clinical results, as measured using the KOOS scores, 
Tegner scores, and qualitative recovery measures, in patients receiving mechanical and RF-
based debridement compared to those receiving mechanical debridement alone (9).  
 
Currently, it is not known if clinical outcomes following treatment of chondral lesions by 
mechanical debridement (i.e. mechanical shaver) or RF-based debridement may equal one 
another.  The primary aim of the proposed study is to evaluate clinical outcomes following 
Radiofrequency-Based Debridement or Mechanical Debridement for subjects requiring 
treatment of a single medial femoral chondral lesion plus partial medial meniscectomy 
procedure. Secondary aims include evaluating imaging and additional clinical outcomes. 
5.2 
Study Device 
ArthroCare Corporation is a wholly-owned subsidiary of Smith & Nephew, Inc. ArthroCare 
Corporation is the legal manufacturer of the study devices. Smith & Nephew distributes the 
study devices. 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 12 of 101 
Document Date: 27OCT2016; Version 4.0 
The Quantum™ 2 System and WEREWOLF™ COBLATION™ System are FDA cleared bipolar, 
radiofrequency electrosurgical systems designed for use in orthopaedic/arthroscopic surgical 
procedures.  
 
The Quantum 2 Controller obtained FDA 510(k) clearance (K082666) on October 15, 2008, 
and Health Canada clearance (License #74846) on December 29, 2009.  ARTHROWANDS™, 
which include the Paragon T2™ ICW Wand, obtained FDA 510(k) clearance (K083306) on 
December 10, 2008, and Health Canada clearance (License #9285) on December 17, 2008. 
The System consists of the following components: 
1. A bipolar radiofrequency Controller; 
2. A reusable, non-sterile Foot Control;  
2a. A reusable, non-sterile wireless Foot Control (optional); 
3. A reusable, non-sterile Power Cord;  
4. A reusable,, non-sterile Patient Cable (optional); and 
5. A disposable, sterile ARTHROWAND Wand (sold separately)  
 
The WEREWOLF™ Controller and FLOW 50™ Wand obtained FDA 510(k) clearance (K162074) 
on August 22, 2016. Health Canada clearance is pending. The System consists of the following 
components: 
1. A bipolar radiofrequency Controller with Integrated Fluid Outflow Regulator; 
2. A non-sterile, reusable wired Foot Control and Power Cord 
3. Sterile, disposable, single-use COBLATION Wands 
5.3 
Mechanism of Action 
Smith & Nephew distributes COBLATION devices for ablation, resection, and coagulation 
of soft tissue and hemostasis of blood vessels in arthroscopic and orthopaedic procedures.   
 
The Paragon T2 ICW Wand is powered by the Quantum 2 Controller and the FLOW 50 
Wand is powered by the WEREWOLF Controller. Both systems use a controlled 
radiofrequency-based plasma process (with the trademark ‘COBLATION’).  In this process, 
radiofrequency energy is used to excite the water molecules in a conductive medium, such as 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 13 of 101 
Document Date: 27OCT2016; Version 4.0 
an electrolyte (saline) solution, to generate excited radicals within precisely focused plasma.  
The energized particles in the plasma have sufficient energy to break molecular bonds (16-
18), excising or dissolving (i.e. ablating) soft tissue at relatively low temperatures (typically 
40ºC to 70ºC).  This technology is a radiofrequency-based technique but its mechanism of 
action is a chemical process and not a function of the radiofrequency energy itself.   
 
The Paragon T2 ICW Wand utilizes T2, or Temperature Technology, which facilitates 
optimal performance by providing a real-time visual indicator when the temperature exceeds 
the recommended 50°C. The FLOW 50 Wand utilizes the Ambient™ feature which provides 
accurate (±3°C) real-time temperature monitoring of the intra-articular irrigating fluid. 
 
These devices also provide the capability for hemostasis, typically delivered through devices 
that can also coagulate bleeding vessels.   
 
6. 
OVERVIEW OF INVESTIGATIONAL PLAN 
This is a prospective, double blinded, multi-center, randomized, controlled study with enrollment 
of 82 randomized subjects at up to 13 study sites. Study duration will be until the last subject 
enrolled reaches 104 weeks post-operative.  
 
Subjects requiring arthroscopic treatment of a single medial femoral chondral lesion plus partial 
medial meniscectomy procedure will be randomly assigned to one of the following device 
groups.  The assignment will be based on a 1:1 ratio (Group I: Group II): 
 
 Group I:  Radiofrequency-Based debridement using the Quantum 2 Controller plus 
Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 Wand (study 
devices) 
 Group II:  Mechanical Debridement (control device) 
 
Study visits will be conducted at the following time points: 
 Visit 1: Screening/Baseline (Day -21 to -1)  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 14 of 101 
Document Date: 27OCT2016; Version 4.0 
 Visit 2: Day 0- Surgery   
 Visit 3: Day 10 (± 3 days)  
 Visit 4: Week 6 (± 5 days)  
 Visit 5: Week 12 (± 7 days)   
 Visit 6: Week 24 (± 14 days) 
 Visit 7: Week 36 (± 14 days)   
 Visit 8: Week 52 (± 28 days)  
 Visit 9: Week 104 (± 56 days)   
 
The Study Flowchart and Follow-Up Assessments table (Table 3) outline the study procedures 
and timelines.  
 
7. 
STUDY OBJECTIVES 
7.1 
Study Purpose 
The purpose of this study is to evaluate changes in clinical and imaging outcomes following 
arthroscopic treatment of a single medial femoral chondral lesion plus partial medial 
meniscectomy by Radiofrequency-Based debridement or Mechanical Debridement in 
subjects ≥ eighteen (18) years of age.  
7.2 
Primary Objective 
The primary objective is to evaluate clinical outcomes following Radiofrequency-Based 
Debridement or Mechanical Debridement for subjects requiring treatment of a single medial 
femoral chondral lesion plus partial medial meniscectomy procedure. 
7.3 
Secondary Objective 
The secondary objectives are to evaluate imaging and additional clinical outcomes.  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 15 of 101 
Document Date: 27OCT2016; Version 4.0 
8. 
STUDY ENDPOINTS 
8.1 
Primary Endpoint 
The primary endpoint is to evaluate the change in Knee and Osteoarthritis Outcomes Scores 
(KOOS) scores at Week 52 post-operative compared to baseline. 
8.2 
Secondary Endpoints 
 Clinical Endpoints 
o Change in International Knee Documentation Committee (IKDC) Subjective 
Knee Evaluation Form scores from baseline  
o Change in International Knee Documentation Committee (IKDC)  Knee 
Examination Form scores from baseline  
o Change in KOOS scores from baseline at Weeks 6, 12, 24, 36 and 104 
o Change in Visual Analogue Scale (VAS) scores from baseline 
o Change in SF-12 scores from baseline 
o Change in EQ-5D-5L scores from baseline 
o Subject Satisfaction at Weeks 52 and 104 
 Imaging Endpoints 
o MRI assessments at Day 10, Weeks 52 and 104 
o ICRS grade of chondral lesion at Day 10, Weeks 52 and 104 
 
9. 
PROTOCOL 
9.1 
Study Design 
This is a non-inferiority, prospective, double blinded, multi-center, randomized, controlled, 
adaptive study design with enrollment of 82 randomized subjects at up to 13 study sites. 
Study duration will be until the last subject enrolled reaches 104 weeks post-operative.  
 
The study will be comprised of two parts: 
Part I:  Part I will require all Investigators perform 1 to 3 procedures using the Quantum 2 
Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 
Wand. Investigators must be qualified by training to perform procedures prior to use of either 
study device. This purpose of Part I will be to minimize variability with the recommended 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 16 of 101 
Document Date: 27OCT2016; Version 4.0 
directions for use established in the instructions for use (IFU).  Part I subjects will be 
followed per protocol follow-up requirements, and will be included in the safety population 
only.  These subjects will be additive (to the safety population) to the 82 randomized subjects 
planned as part of the primary evaluation in Part II. 
 
Part II:  Part II 82 randomized subjects. Each Investigator may initiate enrollment of 
subjects in this part of the study following completion of Part I requirements. 
The Part II study implements a randomized adaptive study design, whereby an interim 
analysis will be conducted for sample size re-assessment. There is no intention of reducing 
the sample size as a result of this interim analysis; however, the sample size may be 
increased to either establish the non-inferiority and/or may be increased sufficiently to 
establish superiority depending on the results of the interim analysis.  
9.2 
Subject Recruitment and Screening 
Subjects will be voluntarily recruited from the Principal Investigator or Sub-Investigator 
population and/or referring physicians. 
 
Subjects who present requiring arthroscopic treatment of a single medial femoral chondral 
lesion plus partial medial meniscectomy procedure will be screened to determine if they meet 
all inclusion and no exclusion criteria. If all entry criteria are achieved, the subject will be 
eligible to participate in the study. All general and indication-specific entry criteria must be 
met prior to study entry. Eligible subjects will be provided with an IRB/REB approved ICF 
for review and signature. Each subject will have a knee physical assessment, and study-
related information will be collected.   
 
All potential subjects screened for eligibility will be listed on the Screening and Enrollment 
Log. The Screening and Enrollment Log will document the date of screening, the results of 
screening, and the primary reason for excluding the subject (e.g., does not satisfy eligibility 
criteria or subject declined). 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 17 of 101 
Document Date: 27OCT2016; Version 4.0 
9.3 
Study Duration and Follow-Up 
Study duration will be until the last subject enrolled reaches 104 weeks post-operative 
treatment. Subjects will be assessed pre-operatively and return post-operatively at Day 10, 
Weeks 6, 12, 24, 36, 52, and 104. At each follow-up visit, the subject questionnaires will be 
administered and AEs and concomitant medication will be reviewed, if applicable. At Day 
10, Weeks 52 and 104 post-operatively, the subjects will complete a MRI of the treated knee.  
 
The Study Flowchart and Follow-Up Assessments table (Table 3) outlines study procedures 
and timelines.  
 
10. SELECTION OF SUBJECTS 
Subjects who meet all of the following criteria will be voluntarily recruited by participating 
Investigators: 
10.1 Inclusion Criteria 
 
Subjects MUST meet ALL of the following criteria to be included in the study: 
1. Given written informed consent on the IRB/REB approved Consent Form specific to 
the study, prior to study participation 
2. Is male or non pregnant female ≥ eighteen (18) years of age 
3. MRI within 9 months of enrollment into this study confirming presence of a medial 
femoral chondral lesion and medial meniscal tear requiring a partial meniscectomy 
(as determined by the Investigator) 
4. Must present with pain in the index knee of moderate or severe (> 30 mm) as 
measured by the VAS 
5. Must be able to understand English (written and oral) 
6. Must be available to come to all study related visits and is physically and mentally 
willing and able to comply with all post-operative evaluations 
7. Must be in general good health (as determined by the Investigator) based on 
screening assessments and medical history 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 18 of 101 
Document Date: 27OCT2016; Version 4.0 
Intra-operative Inclusion Criteria 
Subjects MUST meet ALL of the following criteria to be included in the study: 
1. Arthroscopic confirmation of a lesion requiring treatment meeting the following 
parameters: 
a. Single, treatable chondral lesion, localized to the medial femoral condyle, 
b. ICRS Grade 2 with widely displaceable fibrillation or flaps or Grade 3A, 
c. < 4cm2 in size 
10.2 Exclusion Criteria 
Subjects will be excluded from the study, if they meet ANY one (1) of the following criteria:  
1. 
Body Mass Index (BMI) > 40 or index joint pain is due to BMI (as determined by 
Investigator) 
2. 
Requires bilateral knee surgery 
3. 
Any of the following conditions: 
a. active joint infections 
b. is immunocompromised, has Sickle Cell disease, has a primary bone disease 
(e.g., Paget’s disease) or disorders that may adversely affect the healing 
process, or is terminally ill 
c. inflammatory rheumatoid arthritis or other systemic inflammatory arthritis 
(i.e., gout)  
d. metastatic and/or neoplastic disease 
e. infectious, highly communicable diseases (e.g., active tuberculosis or active 
hepatitis) 
f. coagulation disorder or patient is receiving anti-coagulants 
g. documented evidence of a history (e.g. liver testing) of drug/alcohol abuse 
within 12 months of enrollment into this study  
h. diagnosed with a behavioral condition which could affect their ability to 
accurately comply with the study (e.g. developmental delay, attention deficit 
disorder, and autism)  
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 19 of 101 
Document Date: 27OCT2016; Version 4.0 
4. 
Any of the following conditions in the index limb or joint: 
a. Grade III or greater osteoarthritis as determined by AP radiograph (Kellgren-
Lawrence classification) 
b. systemic steroid therapy or steroid intra-articular therapy within 4 weeks of 
enrollment into this study 
c. intra-articular viscosupplementation within 3 months of enrollment into this 
study 
d. osteomyelitis, septicemia, or other infections that may spread to other areas of 
the body 
e. fractures, osteocysts or osteolysis  
f. recurrent patellar instability (e.g., subluxation or dislocation) 
g. severe Varus or Valgus knee deformities (as determined by Investigator) 
h. symptomatic tear of the lateral meniscus  
i. avascular necrosis  
j. synovial disorders (e.g., pigmented villanodular synovitis) 
k. previous total or partial meniscectomy  
l. requires reconstruction or replacement of medial or lateral meniscus 
m. knee instability, malalignment, or patellar tracking dysfunction  
n. prior treatment for cartilage repair, including but not limited to ACI, 
Mosaicplasty and/or marrow stimulation procedures  
o. prior knee tendon and/or ligament repair or patellar surgery within  6 months 
of enrollment into this study 
5. 
Any of the following conditions in the contralateral limb or joint: 
a. greater than minimal abnormality as shown by clinical exam and/or imaging 
b. scheduled or to be scheduled for surgery over the course of this study 
c. involvement causing abnormal ambulation and non-compliance with 
post-operative rehabilitation guideline 
6. 
The subject has implanted metallic devices (insulin pumps, nerve stimulators, etc), 
medically implanted clips or other electronically, magnetically or mechanically 
activated implants that would contraindicate undergoing an MRI scan of the knee 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 20 of 101 
Document Date: 27OCT2016; Version 4.0 
7. 
The subject has claustrophobia that would inhibit their ability to undergo an MRI 
scan of the index knee  
8. 
Receiving prescription narcotic pain medication for conditions unrelated to the 
index knee condition 
9. 
Cardiac pacemaker or other electronic implant(s) 
10. Pregnant and/or intending to become pregnant during this study period 
11. Participated in a clinical study within 30 days of enrollment into this study, or who is 
currently participating in another clinical study. 
12. Is a prisoner, or is known or suspected to be transient 
13. Is involved with Worker’s Compensation unrelated to the index knee 
14. Is involved with health-related litigation 
 
Intra-operative Exclusion Criteria 
Subjects will be excluded from the study, if they meet ANY one (1) of the following 
criteria:  
1. Has more than 1 chondral lesion requiring treatment  
2. Requires concomitant procedures (i.e., anterior cruciate ligament repair, high tibial 
osteotomy), excluding partial medial meniscectomy 
3. Has a medial meniscal tear not requiring treatment 
4. Has a medial meniscal tear requiring a procedure other than partial meniscectomy 
5. Has a lateral meniscal tear requiring treatment 
 
10.3 Early Withdrawal of Subjects 
10.3.1  When and How to Withdraw Subjects 
Subjects may voluntarily withdraw from the study at any time for any reason. The 
Investigator(s) may elect at any time to withdraw a subject from the study for any reason 
unrelated to the study if such a decision is in the subject’s best medical interest. Subjects 
who experience an AE may also voluntarily withdraw or be withdrawn if deemed in the 
subject’s best medical interest. If a subject discontinues the study prematurely or is 
withdrawn by the Investigator(s), data collected up to the time of withdrawal will be used 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 21 of 101 
Document Date: 27OCT2016; Version 4.0 
if applicable for analysis. The primary reason for termination or discontinuation will be 
documented on the End of Study CRF. Subjects who are withdrawn for any reason from 
the study after intervention will not be replaced. 
 
10.3.2 Data Collection and Follow-up for Withdrawn Subjects 
Subjects who withdraw consent and refuse to complete the follow-up assessment, fail to 
adhere to protocol requirements, or die during the follow-up phase will be considered off-
study at that time. Attempts will be made to retrieve any follow-up data, in particular, 
regarding possible AEs at the time of study discontinuation. If the Investigator(s) reports 
a subject as lost to follow-up, the Clinical Research Associate (CRA) will ensure that 
documentation is made regarding the reason(s) this has occurred and will ensure that 
every attempt is made by the Investigator(s) to contact the subject to determine subject 
status. Appropriate documentation will consist of at least two documented attempts at 
contact via telephone, followed by an attempt to contact via a registered US/Canada post 
letter. 
 
10.3.3 Study Site Termination 
A specific study site in this multi-center study may also warrant termination under the 
following conditions: 
 Failure of the Investigator to enroll subjects into the study at an acceptable rate; 
 Failure of the Investigator to comply with ICH guidelines, IRB/REB policies and 
procedures and/or regulatory body(s) regulations; 
 Knowingly submitting false information from the study site to the Sponsor or its 
designee, IRB/REB, and/or regulatory body(s), as applicable; or 
 Insufficient adherence to protocol requirements. 
 
10.4 Prior and Concomitant Therapy 
Information on concomitant medications will be recorded on the Concomitant Medication 
CRF. Any medication used by the subject will be considered concomitant medication (e.g., 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 22 of 101 
Document Date: 27OCT2016; Version 4.0 
aspirin, Tylenol, vitamins, dietary supplements, etc). Any changes in medication must be 
noted on the Concomitant Medication CRF.  
 
Any other investigational drug or approved therapy for investigational use is not permitted 
during study participation.  
 
11. STUDY PROCEDURES 
11.1 Study Interventions 
11.1.1 Single Medial Femoral Chondral Lesion Treatment plus Partial Medial Meniscectomy 
Procedure 
A diagnostic arthroscopic evaluation will be conducted to confirm the area of treatment.  
If all arthroscopic eligibility criteria are met, the subject will be randomized to one of the 
following two treatments: 
 Radiofrequency-Based Debridement (study devices) 
 Mechanical Debridement (control device) 
 
If randomized to Radiofrequency-Based Debridement, the subject will receive the 
Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus 
FLOW 50 Wand. 
11.2 Outcome Measures 
11.2.1 Subject Questionnaires 
For examples of subject questionnaires, refer to Appendix B. 
 Knee Injury and Osteoarthritis Outcome Score (KOOS) 
 International Knee Documentation Committee Assessment (IKDC) Subjective 
Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 Visual Analogue Scale (VAS), knee pain 
 Subject Satisfaction 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 23 of 101 
Document Date: 27OCT2016; Version 4.0 
11.2.2 Physical Assessment  
 Physical Assessment - Knee (warmth, swelling, skin changes, evidence of 
infection) 
 IKDC Knee Examination Form 
 
11.2.3 Magnetic Resonance Imaging (MRI) 
All MRI assessments will consist of double reads completed by blinded radiologists.  The 
following MRI assessments will be used to evaluate subjects at Day 10, Weeks 52 and 
104 post-operatively. 
 Quantitative and semi-quantitative assessment of knee morphology, including but 
not limited to: 
o Cartilage Morphology, Cartilage Signal, Osteophytes, Bone Marrow Edema, 
Subarticular Cysts, Effusion, Loose Bodies 
o Characterization of Cartilage 
 International Cartilage Repair Score (ICRS)  
 
11.2.3.1 Appropriateness for Measurements – MRI 
MRI is increasingly being used in the clinical setting as a non-invasive tool for the 
diagnosis and evaluation of cartilage lesions in the knee.  A variety of imaging 
sequences may be selected to optimize the contrast between the cartilage tissue and 
neighboring tissue making it more accurate than arthroscopic observation, which has 
a limited field of view. In addition, MR imaging, when performed with appropriate 
high contrast, high resolution pulse sequences, may provide quantitative information 
regarding specific dimensions of various tissues in the knee. Acquired MR images 
may be re-evaluated at a later date. 
 
MR imaging will be performed according to established acquisition guidelines. 
 
11.3 Visit Summary 
11.3.1 Visit 1:  Screening/Baseline (days -21 to -1) 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 24 of 101 
Document Date: 27OCT2016; Version 4.0 
All potential subjects screened for eligibility will be listed on the Screening and 
Enrollment Log. The Screening and Enrollment Log will document the date of screening, 
the results of screening, and the primary reason for excluding the subject (e.g., does not 
satisfy eligibility criteria or subject declined). 
If all inclusion criteria and no exclusion criteria are met and the eligible subject agrees to 
participate in the study, he/she will be required to sign an IRB/REB approved ICF. After 
signing the ICF, each subject will have a knee physical assessment and study-related 
information will be collected. 
The assessments to be performed at Visit 1 include, but are not limited to: 
 Confirm written informed consent, prior to any screening procedures 
 Inclusion/exclusion criteria 
 Demographics (e.g., age, sex, work status, nicotine use) 
 Concomitant medication, if applicable 
 Medical and surgical history 
 Physical Assessment – Knee 
 IKDC Knee Examination Form  
 Mechanism of injury 
 Screening number assignment 
 Confirm Visit 2 (surgery) scheduled within 1-21 days after screening 
 
Imaging Assessment: 
Pre-operative imaging include: 
 Weight-bearing Anterior / Posterior 
 Weight-bearing Lateral 
 Merchant 
 Weight-bearing posteroanterior radiograph 
 Standing Long Leg Alignment 
 MRI (within 9 months of enrollment into this study ) 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 25 of 101 
Document Date: 27OCT2016; Version 4.0 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.2 Visit 2:  Surgery (Day 0) 
If the Investigator(s) discovers the presence of a condition at the time of surgery that 
would render the subject ineligible for study participation, the subject should be 
considered as an intra-operative failure and be discontinued from the study. The subject 
should receive the standard of care as determined by the Investigator(s).   
 
The primary reason for termination or discontinuation will be documented on the End of 
Study CRF. 
 
If the subject continues to meet eligibility, the data collected will include, but not be 
limited to: 
 Subject randomization 
 Date and time of surgery 
 Device information 
 Tourniquet time 
 Duration of surgery (start and stop hh:mm from the first incision to the final 
closure) 
 Anesthesia type and time of administration 
 Adverse Events, if applicable 
 Concomitant medication, if applicable 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 26 of 101 
Document Date: 27OCT2016; Version 4.0 
11.3.2.1 Surgical Procedure 
 Randomization  
o The subject will be randomized to receive: 
 study device, or 
 control device 
if they continue to meet  all of the following: 
 Single, treatable chondral lesion, localized to the medial femoral 
condyle, 
 ICRS Grade 2 with widely displaceable fibrillation or flaps or Grade 
3A, 
  < 4cm2 in size 
and  
 a medial meniscus tear requiring partial meniscectomy 
 End of Study 
o Subjects will not be randomized and be considered off study if they meet any 
one (1) of the following intra-operative exclusion criteria: 
 Has more than 1 chondral lesion requiring treatment  
 Requires concomitant procedures (i.e., anterior cruciate ligament 
repair, high tibial osteotomy), excluding partial medial meniscectomy 
 Has a medial meniscal tear not requiring treatment 
 Has a medial meniscal tear requiring a procedure other than partial 
meniscectomy 
 Has a lateral meniscal tear requiring treatment  
o Subjects will not be randomized and be considered off study if they do not 
meet any one (1) of the following intra-operative inclusion criteria: 
1.   Arthroscopic confirmation of a lesion requiring treatment meeting   
the following parameters: 
a. Single, treatable chondral lesion, localized to the medial femoral 
condyle, 
b. ICRS Grade 2 with widely displaceable fibrillation or flaps or 
Grade 3A, 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 27 of 101 
Document Date: 27OCT2016; Version 4.0 
c. < 4cm2 in size 
o An End of Study Case Report Form (CRF) will be completed 
 
11.3.3 Visit 3:  Day 10 Follow-Up (+/- 3 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 Admission/Discharge information  
 Adverse Events, if applicable 
 Concomitant medication, if applicable 
o Any changes in concomitant medication 
 Compliance with Post-operative Rehabilitation Guideline 
 
Imaging assessment: 
Imaging includes: 
 MRI 
 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.4 Visit 4:  Week 6 Follow-up (+/- 5 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form - Subject dependent 
 Adverse Events, if applicable 
 Concomitant medication, if applicable 
o Any changes in concomitant medication 
 Compliance with Post-operative Rehabilitation Guideline 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 28 of 101 
Document Date: 27OCT2016; Version 4.0 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.5 Visit 5:  Week 12 Follow-Up (+/- 7 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form 
 Adverse Events, if applicable 
 Concomitant medication, if applicable 
o Any changes in concomitant medication 
 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.6 Visit 6: Week 24 Follow-Up (+/- 14 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form 
 Adverse Events, if applicable 
 Concomitant medication, if applicable 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 29 of 101 
Document Date: 27OCT2016; Version 4.0 
o Any changes in concomitant medication 
 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.7 Visit 7:  Week 36 Follow-Up (+/- 14 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form 
 Adverse Events, if applicable 
 Concomitant medication, if applicable 
o Any changes in concomitant medication 
 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 
11.3.8 Visit 8:  Week 52 Follow-Up (+/- 28 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 30 of 101 
Document Date: 27OCT2016; Version 4.0 
 Adverse Events 
 Concomitant medication 
o Any changes in concomitant medication 
Imaging assessment: 
Imaging includes: 
 Standing Long Leg Alignment 
 MRI 
 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 Subject Satisfaction 
 
11.3.9 Visit 9:  Week 104 Follow-Up (+/- 56 day(s)) 
The data collected will include, but not be limited to: 
 Physical Assessment - Knee 
 IKDC Knee Examination Form 
 Adverse Events 
 Concomitant medication 
o Any changes in concomitant medication 
 
Imaging assessment: 
Imaging includes: 
 MRI 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 31 of 101 
Document Date: 27OCT2016; Version 4.0 
Subject self-reported questionnaires: 
Subjects will be asked to complete the following questionnaires: 
 KOOS 
 IKDC Subjective Knee Evaluation Form 
 SF-12 
 EQ-5D-5L 
 VAS, knee pain 
 Subject Satisfaction 
 
11.3.10 Optional Follow-Up Visit, Unscheduled Visit Procedures  
Subjects that have pre-scheduled surgical visits not involving the affected or contralateral 
limb (e.g., gallbladder removal, shoulder arthroscopy), and subjects that have additional 
visits beyond the study-scheduled visits and within the standard of care do not need 
documentation, unless associated with an AE (e.g., generalized AE or device/treatment-
related AE). 
 
11.3.11 Post-operative Rehabilitation Guideline 
Guidelines for post-operative rehabilitation are included in the Investigator Site File. 
 
12. STATISTICAL ANALYSIS  
This section presents general information about statistical methodologies and concepts such as 
statistical power, sample size, randomization and a brief analysis methodology, as well as some 
data conventions. Detailed descriptions of the statistical analysis methods and data conventions 
that will be used in this study will be provided as a separate document; i.e., the Statistical 
Analysis Plan (SAP).   
12.1 Treatment Groups  
The eligible subjects will be randomized to one of the following two treatment groups: 
 Group I:  Radiofrequency-Based debridement (study devices) 
 Group II:  Mechanical Debridement (control device) 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 32 of 101 
Document Date: 27OCT2016; Version 4.0 
If randomized to Radiofrequency-Based Debridement, the subject will receive the Quantum 2 
Controller plus Paragon T2 ICW Wand or the WEREWOLF Controller plus FLOW 50 
Wand. Investigators must be qualified by training to perform procedures prior to use of either 
study device. 
 
12.2 Description of Study Endpoints  
12.2.1 Primary Efficacy Endpoint 
Change in Knee and Osteoarthritis Outcomes Scores (KOOS) scores at Week 52 post-
operative compared to baseline. 
 
12.2.2 Secondary Endpoints: 
There are two sets of endpoints that are known and well established in this patient 
population, the clinical and imaging endpoints.  Both of these will be assessed in this 
protocol. 
o Clinical Endpoints 
o Change in International Knee Documentation Committee (IKDC) 
Subjective Knee Evaluation Form scores from baseline  
o Change in International Knee Documentation Committee (IKDC)  Knee 
Examination Form scores from baseline  
o Change in KOOS scores from baseline at Weeks 6, 12, 24, 36 and 104 
o Change in Visual Analogue Scale (VAS) scores from baseline 
o Change in SF-12 scores from baseline 
o Change in the EQ-5D-5L scores from baseline 
o Subject Satisfaction at Weeks 52 and 104 
o Imaging Endpoints 
o MRI assessments at Day 10, Weeks 52 and 104 
o ICRS grade of chondral lesion at Day 10, Weeks 52 and 104 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 33 of 101 
Document Date: 27OCT2016; Version 4.0 
12.2.3 Safety Assessments  
Safety will be assessed through reports of Adverse Events.  
12.3 Sample Size Determination, Power calculation, and Rationale 
This study will be conducted in a two parts. There is no power calculation for the Part I 
study. In the Part II study subjects will be randomized to one of the two treatment groups 
in a 1:1 ratio.  
 
A total of 82 subjects (41 in the study device group and 41 in the control device group) 
will be randomized in an effort to assure that seventy (70) subjects (i.e., 35 subjects per 
group) complete the study.  
 
PASS version 2011, is used for this sample size and power calculation. The requirement 
of 70 subjects (35 active and 35 control) is based on achieving 80% statistical power to 
detect a non-inferiority margin difference of 8 points between the two groups (10). For 
the same 80% statistical power, and significance level (alpha) of 0.05 two-sided test; one 
may choose different number of subjects depending on the expected and observed KOOS 
score and the acceptance of the non-inferiority delta. These are depicted in Figure 12-1 
below. 
 
The discontinuation rate is predicted to be no more than 15%. To accommodate the 
potential discontinuations, 82 randomized subjects (41 in the study device group and 41 
in the control device) are needed for this study.  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 34 of 101 
Document Date: 27OCT2016; Version 4.0 
Figure 12-1: Sample Size and Statistical Power Calculation 
 
 
12.4 Randomization 
This is a multi-center, randomized clinical study. The randomization will be by-site 
randomization to assure balanced number of subjects between the study devices and control 
device group in each investigational site.   
 
The randomization will be in 1:1 ratio (i.e., study devices: control device). In each 
investigational site, subjects who are eligible for randomization will be randomized in a 
double-blind manner to a device. 
   

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 35 of 101 
Document Date: 27OCT2016; Version 4.0 
12.5 Blinding 
12.5.1 Subject Blinding 
Subjects will be blinded to treatment assignment until they complete the course of the 
study.  All efforts will be made to keep the subject blinded.  Should a subject undergo 
subsequent arthroscopy for recurrent or new symptoms, withdraw from the study, or be 
terminated from the study, the blinded assignment will be revealed to the subject and the 
Investigator will provide care as standard and usual. 
 
12.5.2 Study MRI Blinding 
All MRI scans will be transferred to the study radiologists in DICOM format.  All subject 
information will be masked to ensure blinding.  The study radiologists reviewing the 
scans will also be blinded to the treatment received by the subject.  MRI scans will be 
evaluated at Day 10, Weeks 52 and 104 post-operative treatment.  All efforts will be 
made to keep the study radiologists blinded to treatment assignment information by 
restricting access to related information. 
 
12.5.3 Interim Analysis (IA) 
One interim analysis is planned to be conducted for this study.  This interim analysis will 
be primarily for sample size recalculation of the Part II study.  The study will not be 
stopped due to the efficacy results, and no hypotheses testing will be conducted in this IA 
to assess the differences between the two groups. 
 
This interim analysis is planned to be conducted when 50% of subjects are randomized 
and completed the Week 24 post-operative follow up evaluations.   
The interim analysis will be conducted under the auspices of an independent Data Safety 
Monitoring Board (DSMB). 
 
There is no intention of decreasing the sample size; however, the sample size may be 
increased to either establish the non-inferiority and/or may be increased sufficiently to 
establish superiority depending on the results of the interim analysis.  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 36 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
12.5.3.1 Procedures for Interim Analysis  
The data to be used in the interim analysis and the treatment assignment of each 
randomized subject will be given to the independent statistician. Using this data, the 
independent statistician will calculate the following metrics for the primary end point: 
 difference in change in KOOS scores between the treatment groups 
 change in KOOS score from baseline in Group I and the observed number of subjects 
in the group  
 change in KOOS score from baseline in Group II and the observed number of 
subjects in the group  
 dropout rate at the time of the IA 
  statistical power of the study at the time of the Interim Analysis (using a conditional 
power approach)  
 conditional power in this IA (CP) will be calculated according to the following 
formula (Chen 2004 [11]) using primary endpoint data from the ITT population.  
CP(f1,z1) = Φ { z1 / 
   –   za  / 
 } 
Where: 
 CP(f1,z1)  is the conditional power at the IA  
 Φ{.} is the cumulative distribution function of a standard Normal distribution (μ=0, 
σ2 = 1)  
 f1 is the fraction of patients enrolled and used in the interim analysis before decision 
of increasing the sample size 
 zα is the upper α quintile for standard Normal distribution  
 z1 is the standardized Normal  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 37 of 101 
Document Date: 27OCT2016; Version 4.0 
12.5.3.2 Rules and Method for Increasing Sample Size  
The sample size will be adjusted only if the conditional power at the time of the Interim 
Analysis is 50% or more and less than 80%. The sample size will be recalculated based 
on the observed difference between the treatment groups.  
If the conditional power is larger than 50%, then the sample size will be adjusted upward 
and no Type I error rate adjustment will be made to the final analysis. 
If the conditional power is less than 50%, the Type I error rate will be inflated and 
statistical adjustment will be made to the final analysis, an adjustment to the final p-value 
will be made as follows:  
p-value =2 [ 1- 
 | f2 ½  z1 + (1-f2 ) ½  z2 | } ] 
where:   
P-value is the adjusted target p-value at the end of the study reflecting the adjustment for 
increasing the study size at the interim analysis  
n1, is the sample size at the time of the interim analysis (n1 =  ngp1 + ngp2)  
n2 is the re-calculated sample size to be enrolled after the interim analysis 
 f2 =n1 / (n1+n2)  is the fraction of the newly planned sample size at the IA  
z1 is the observed z score at the time of the interim analysis  
z2 is the observed z value of the z score only based on the data collected after the interim 
analysis  
 
12.5.4 General Statistical Considerations  
All collected study data will be presented in subject data listings. Statistical analyses will 
be performed using SAS® for Windows, version 9.3 or later. Descriptive statistics (n, 
mean, standard deviation, median, minimum and maximum) will be calculated by 
treatment group for continuous variables. Frequencies and percentages will be presented 
by treatment group for categorical variables. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 38 of 101 
Document Date: 27OCT2016; Version 4.0 
12.6 Analysis Populations  
12.6.1 Intent-to-Treat Population 
The Intent-to-Treat (ITT) population is defined as all randomized subjects. The Intent-to-
Treat population will be the primary population for the analysis of the primary and 
secondary endpoints. 
 
12.6.2 Per Protocol Population 
The Per Protocol (PP) population is defined as all randomized subjects who were not 
associated with a major protocol violation.  
 
12.6.3 Safety Population 
The Safety population is defined as any subject receiving the device/treatment. This 
population will be used for the analysis of safety parameters.  This population includes 
the subjects from both Parts I and II of the study. 
12.7 Statistical Methods  
A SAP will be developed and approved before the database is locked. The SAP will present 
the detailed statistical methodology to be used in analyzing the efficacy and safety data from 
this study. No inferential statistics will be performed on the baseline and safety data 
summaries.  
 
12.7.1 Subject Disposition  
The disposition of all subjects who sign an ICF will be provided. The numbers of subjects 
screened, randomized, completed, and discontinued during the study, as well as the 
reasons for all post-randomization discontinuations will be summarized by 
device/treatment group. Disposition and reason for study discontinuation will also be 
provided as a by-subject listing.   

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 39 of 101 
Document Date: 27OCT2016; Version 4.0 
12.7.2 Demographic and Baseline Characteristics  
Demographics and baseline characteristics (i.e., medical history, AP/Lateral/ Merchant/ 
posteroanterior radiograph View, etc.) will be summarized by device/treatment group using 
appropriate descriptive statistics and/or presented as by-subject listing on the safety 
population. 
 
12.7.3 Protocol Deviations 
The deviations occurring during the clinical study will be summarized and/or presented 
as/by-subject listing.  
 
12.7.4 Prior and Concomitant Medications  
All prior and concomitant medications recorded in the Case Report Form will be coded 
using the most recent version of WHO Drug dictionary. Descriptive summaries, by 
device/treatment group, will be prepared using the coded term.  All prior and concomitant 
medications recorded in the Case Report Form will be listed.   
 
12.7.5 Efficacy Analyses 
12.7.5.1 Primary Analysis  
Primary Endpoint:  
The primary analysis will be conducted on the Intent-to-treat (ITT) population. The 
change in Knee and Osteoarthritis Outcomes Scores (KOOS) from baseline will be 
compared between the device/treatment groups using Repeated Measures Analysis of 
Covariance.    
 
Secondary Endpoints:    
The secondary endpoints will be analyzed using Analysis of Covariance (ANCOVA) 
models, or logit model to assess the differences between the two device/treatment 
groups depending on the nature of the endpoint.  The Baseline KOOS will be used as 
Covariates. 
 Clinical Endpoints 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 40 of 101 
Document Date: 27OCT2016; Version 4.0 
o Change in International Knee Documentation Committee (IKDC) 
Subjective Knee Evaluation Form scores from baseline  
o Change in International Knee Documentation Committee (IKDC)  Knee 
Examination Form scores from baseline  
o Change in KOOS scores from baseline at Weeks 6, 12, 24, 36 and 104 
o Change in Visual Analogue Scale (VAS) scores from baseline 
o Change in SF-12 scores from baseline 
o Change in the EQ-5D-5L scores from baseline 
o Subject Satisfaction at Weeks 52 and 104 
 Imaging Endpoints 
o MRI assessments at Day 10, Weeks 52 and 104 
o ICRS grade of chondral lesion at Day 10, Weeks 52 and 104 
 
12.7.5.2 Supportive Analysis  
To assess the consistency of the Primary Analysis results, supportive analysis will be 
conducted using the Per Protocol (PP) population. Statistical methodology for the 
supportive analyses will be the same as that of the primary analysis, with the 
exception of the analysis population used.   
 
12.7.6 Safety Analyses  
The Safety population will be used for the analysis of safety outcomes.  All safety 
assessments will be tabulated and no hypothesis testing will be conducted in this analysis. 
For continuous variables data will be summarized by device/treatment group using n, 
mean, standard deviation, median, minimum and maximum values. For categorical 
variables data will be summarized by device/treatment group using frequency and 
percentage.     

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 41 of 101 
Document Date: 27OCT2016; Version 4.0 
12.7.6.1 Adverse Events / Adverse Device Effects 
Adverse Events will be coded using most recent version of MedDRA. Treatment 
Emergent AE’s (TEAE) are defined as events with an onset on or after the first 
randomized treatment. TEAEs will be summarized by treatment group, System Organ 
Class, and preferred term. The following TEAE summaries will be provided: 
 TEAEs by severity grade 
 TEAEs by relationship to study device. 
 
In addition, separate summaries of Serious Adverse Events will also be presented. 
The total number of subjects with at least one AE/ADE and the number of AEs/ADEs 
will be derived.  If more than one AE/ADE with the same preferred term occurs 
within a subject during the study period, they will be counted only once for that 
subject using the worst reported severity and causal relationship to the intervention. 
AEs/ADEs will also be tabulated versus worst severity and worst relationship to the 
intervention.  
 
Symptoms, AEs recorded before administration of intervention will only be presented 
in listings. 
12.7.6.2 Physical Assessment - Knee 
All knee physical assessment findings will be listed and/or summarized.   

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 42 of 101 
Document Date: 27OCT2016; Version 4.0 
13. SAFETY AND ADVERSE EVENTS 
13.1 Definitions 
 
13.1.1 Adverse Event 
An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated 
with the use of a study device, whether or not considered related to the study device. 
13.1.2 Adverse Device Effect 
ADEs are AEs caused by or related to the device. 
 
13.1.3 Serious Adverse Events 
Events are classified as serious if they meet any of the following criteria (in accordance 
with the recommendations of ICH [Federal Register, October 7, 1997, Vol. 62, No. 194, 
pp 52239-45]): 
 
 Results in death, 
 Is life-threatening (NOTE:  the term “life-threatening” in the definition of 
“serious” refers to an event in which the subject was at risk of death at the time of 
the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe), 
 Requires inpatient hospitalization or prolongation of existing hospitalization, 
 Results in persistent or significant disability/incapacity,  
 Is a congenital anomaly/birth defect 
 
Additionally, events are classified as serious if they meet any of the following criteria: 
 Requires intervention to prevent permanent impairment/damage, or 
 Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered a serious adverse device effect when, 
based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes listed 
above.  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 43 of 101 
Document Date: 27OCT2016; Version 4.0 
13.1.4 Unanticipated Adverse Device Effect 
An Unanticipated Adverse Device Effect is described as any serious adverse effect on 
health or safety or any life-threatening problem or death caused by or associated with a 
device, if that effect, problem, or death was not previously identified in nature, severity, 
or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects (21 CFR 812.3(s)). 
 
13.2 Recording of Adverse Events 
At each contact with the subject, the Investigator must seek information on AEs through 
questioning. Information on all AEs should be recorded immediately in the source document 
and in the appropriate AE module of the CRF. All clearly related signs, symptoms, and 
abnormal diagnostic procedures results should be recorded in the source document, though 
should be grouped under one diagnosis.   
 
All AEs occurring during the study must be recorded in standard medical terminology. The 
clinical course of each event should be followed until resolution, stabilization, or until it has 
been determined that the study intervention or participation is not the cause. All unresolved 
AEs should be followed by the Investigator until the events are resolved, the subject is lost to 
follow-up, through the end of the study, or until it has been determined that the study 
intervention or participation is not the cause (whichever timing occurs first). Any Serious 
Adverse Event (SAE) that occurs until thirty (30) days after the study and is considered to be 
related to the study device or study participation should be recorded and reported 
immediately. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 44 of 101 
Document Date: 27OCT2016; Version 4.0 
13.3 Reporting  
13.3.1 Adverse Event Reporting Period 
The study period during which AEs must be reported is defined as from the initiation of 
any study treatment or randomization through the end of the study intervention follow-
up.  
 
13.3.2 Reporting Adverse Events 
Any AE (clinical sign, symptom, or disease) temporally associated with the use of this 
study device, whether or not considered related to the study device, shall be documented 
on the AE CRF, except those physical assessment findings that are considered to be 
clinically insignificant. All AEs meeting the above noted criteria reported by the subject 
or observed by the Investigator will be individually listed. The description of the event 
(confirmed diagnosis, if available), date of onset, date of resolution, severity and 
relationship to study device, action taken, outcome, and seriousness will be reported. 
The Investigator will evaluate all AEs as follows:  
 
CTCAE Grade (Intensity) Assessment 
The guidelines outlined in CTCAE v4.03 will be used for assessing the intensity of the 
event. The general guidelines for assessing the AE grade appear below.  Full guidelines 
may be obtained at http://evs.nci.nih.gov/ftp1/CTCAE. 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 45 of 101 
Document Date: 27OCT2016; Version 4.0 
 
Table 3: CTCAE v4.03 General Guidelines 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
(ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE.‡ 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, 
etc. 
†Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
‡Unlike the AE outcome assessment (see Section 13.3.2), a subject may have more than one Grade 5 event. 
 
-Common Terminology Criteria for Adverse Events (CTCAE), v4.03: June 14, 2010 
 
 
 
Causality Assessment 
Adverse Events will be assigned a relationship (causality) to the study device/treatment.  
The Investigator will be responsible for determining the relationship between an AE and 
the study device/treatment.  The type of event, organ system affected, and timing of onset 
of the event will be factors in assessing the likelihood that an AE is related to the study 
device/treatment.  Relationship of AEs to study device/treatment will be classified as 
follows: 
o Not Related: Any reaction that does not follow a reasonable temporal sequence 
from administration of the study device AND that is likely to have been produced 
by the subject’s clinical state or other modes of therapy administered to the 
subject. 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 46 of 101 
Document Date: 27OCT2016; Version 4.0 
o Related: A reaction that follows a reasonable temporal sequence from 
administration of the study device AND that follows a known response pattern to 
the suspected device. 
 
 Action Taken as a Result of the Event 
The action taken in terms of treatment provided will be as either: none, medication 
administered, therapy administered, surgery, study treatment unblinded, or other (with a 
specification). 
 
 Outcome Assessment 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, 
ongoing, lost to follow-up or death.  Only one AE per subject is allowed to have an 
outcome assessment as “death.”  If there are multiple causes of death for a given subject, 
only the primary cause of death will have an outcome of death. 
 
13.3.3 Reporting Serious Adverse Events and Incidents 
For any SAE, the Principal Investigator must submit a completed AE CRF via email to 
the Sponsor’s Medical Monitor, within 24 hours of becoming aware of the event and send 
the completed Serious Adverse Event/Unanticipated Adverse Device Effect 
(SAE/UADE) Report via email to the Sponsor’s Medical Monitor within 48 hours. In 
addition, all IRB/REB reporting requirements will be followed. 
 
The Principal Investigator shall make an accurate and adequate report of any SAEs or 
Unanticipated Adverse Device Effects (UADE). The Principal Investigator shall 
document any such report on the appropriate CRF and email any initial or follow-up 
report to the Sponsor‘s Medical Monitor and to the IRB/REB (as applicable) that has 
reviewed and continues to review the study. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 47 of 101 
Document Date: 27OCT2016; Version 4.0 
 Pre-existing Condition: 
A pre-existing condition, other than the condition being treated, is one that is 
present at the start of the study. A preexisting condition should be recorded as an 
AE if the frequency, intensity, or the character of the condition worsens during 
the study. 
 
 General Physical Assessment Findings: 
At screening, any clinically significant abnormality should be recorded as a 
preexisting condition. At the end of the study, any new clinically significant 
findings/abnormalities that meet the definition of a SAE must be recorded and 
documented as a SAE.  
 
 Post-study Serious Adverse Event: 
All unresolved SAEs should be followed by the Investigator until the events are 
resolved, the subject is lost to follow-up, through the end of the study, or until it 
has been determined that the study intervention or participation is not the cause 
(whichever timing occurs first). At the last scheduled visit, the Investigator should 
instruct each subject to report any subsequent event(s) until thirty (30) days after 
study completion that the subject or the subject’s personal physician believes to 
be related to participation in the study. The Investigator should notify the 
Sponsor’s Medical Monitor of any death or SAE occurring at any time after a 
subject has discontinued or terminated study participation that is related to the 
study.   
 
 Hospitalization, Prolonged Hospitalization, or Surgery: 
Any medical conditions that occurs after randomization and results in 
hospitalization or prolonged hospitalization should be documented and reported 
as a SAE unless specifically instructed otherwise in this protocol. Any condition 
responsible for surgery should be documented as a SAE if the condition meets the 
criteria for a SAE.  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 48 of 101 
Document Date: 27OCT2016; Version 4.0 
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are 
reported as a SAE in the following circumstances: 
 
 Hospitalization or prolonged hospitalization for diagnostic or elective 
surgical procedures for a preexisting condition.  
 Hospitalization or prolonged hospitalization for therapy of the target 
disease of the study, unless it is a worsening or increase in frequency of 
hospital admissions as judged by the Investigator (e.g., secondary post-
operative hemorrhage). 
 
13.3.3.1 Investigator Reporting:  Notifying the Sponsor 
Any SAE or UADE must be reported to the Sponsor’s Medical Monitor by 
submitting a completed AE CRF via email within 24 hours of becoming aware of the 
event:  
 
MEDICAL MONITOR CONTACT INFORMATION 
Joseph W. Krotec, MD 
Chiltern International Ltd. / Theorem Clinical Research 
1016 West Ninth Avenue  
King of Prussia, PA 19406  
Email: medicalsafety@theoremclinical.com  
Phone: +1 (484) 832-8770 
 
Within 48 hours after the initial report, the Investigator must provide further 
information via email to the Sponsor’s Medical Monitor on the SAE or UADE in the 
form of a written narrative. This should include a copy of the completed SAE/UADE 
Report Form and any other related diagnostic information that will assist in the 
understanding of the event. Significant new information on ongoing SAEs should be 
provided promptly to the Sponsor’s Medical Monitor. All identifiable reference to the 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 49 of 101 
Document Date: 27OCT2016; Version 4.0 
subject except for the subject screening number will be redacted from any report sent 
to the Sponsor’s Medical Monitor.  
 
13.3.3.2 Investigator Reporting: Notifying the IRB/REB 
Investigators are responsible for safety reporting to their IRB/REB. Investigators are 
responsible for complying with their IRB/REB’s reporting requirements for SAEs, 
though they must notify their IRB/REB within 10 working days of becoming aware 
of the event for any potential UADEs (21 CFR 812.150(a)(1)). The Sponsor or its 
designee will provide safety reports to the Investigators to assist with reporting to the 
IRB/REB’s. Copies of each safety report and documentation of IRB/REB notification 
and receipt will be kept in the Trial Master File/Study Master File. 
 
13.3.3.3 Reporting Deaths 
The following describes the Investigator reporting requirements in the event of a 
death, considered a SAE, which occurs during the course of a study: 
 Notify the Sponsor’s Medical Monitor by submitting a completed AE CRF via 
email within 24 hours of becoming aware of the event, 
 Provide the completed SAE/UADE Report Form via email to the Sponsor’s 
Medical Monitor within 48 hours of the event, 
 Notify the IRB/REB of the death per IRB/REB reporting requirements. 
 
Should the Investigator determine the death to be device-related and unanticipated, it 
is considered an UADE, and the following Investigator reporting requirements should 
be followed: 
 Notify the Sponsor’s Medical Monitor by submitting a completed AE CRF via 
email within 24 hours of becoming aware of the event, 
 Provide the completed SAE/UADE Report Form via email to the Sponsor’s 
Medical Monitor within 48 hours of the event, 
 Notify the IRB/REB of the death per IRB/REB reporting requirements, but no 
later than 10 days of becoming aware of the event. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 50 of 101 
Document Date: 27OCT2016; Version 4.0 
 
13.3.4 Informed Consent Violation Reporting 
If the Investigator uses the study device without obtaining informed consent, the 
Investigator shall report such use to the Sponsor and the reviewing IRB/REB within 5 
working days after the use occurs (21 CFR 812.150(a)(5)).  
 
13.3.5 Protocol Deviation Reporting 
The Investigator shall notify the Sponsor and the reviewing IRB/REB of any deviation 
from the protocol to protect the life or physical well-being of a subject in an emergency. 
Such notice shall be given as soon as possible, but in no event later than 5 working days 
after the emergency occurred (21 CFR 812.150(a)(4)).  All other deviations from the 
protocol will be reported on the appropriate CRF and reported to the IRB/REB, if 
required.  Every effort shall be made to comply with the requirements of the protocol to 
avoid deviations.   
 
13.3.6 Progress Reports 
The Investigator shall submit Progress Reports on the study to the Sponsor and the 
reviewing IRB/REB at regular intervals, but in no event less often than yearly (21 CFR 
812.150(a)(3)).  
 
13.3.7 Final Report 
The Investigator shall, within 3 months after termination or completion of the study or 
the Investigator's part of the study, submit a Final Report to the Sponsor and the 
reviewing IRB/REB (21 CFR 812.150(a)(6)). 
13.4 Unblinding Procedures 
Data are to remain blinded per protocol throughout the study. However, unblinding of 
subjects will occur by the DSMB, data manager and/or statisticians in the event of a SAE that 
is deemed related to the study intervention.  If time permits, the Investigator should make 
every attempt to contact the Sponsor and/or trial Medical Monitor before unblinding any 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 51 of 101 
Document Date: 27OCT2016; Version 4.0 
subjects’ device/treatment. For emergent unblinding, appropriate study personnel must 
contact the Sponsor and the Medical Monitor as soon as possible after the incident to report 
the details surrounding the emergency unblind and to receive instruction on follow-up 
procedures. 
13.5 Data Safety Monitoring Board 
The Data and Safety Monitoring Board (DSMB) consists of a group of individuals, appointed 
by the Sponsor or its designee, with pertinent expertise that will review accumulated data at 
the interim analysis from the study. The DSMB advises the Sponsor regarding the continuing 
safety of subjects and those yet to be voluntarily recruited to the study, as well as the 
continuing validity and scientific merit of the study. Unblinded data reviewed by the DSMB 
will be kept confidential and protected from inadvertent or inappropriate access by the 
Sponsor or its designee. Following review of data generated from the interim analysis, the 
DSMB may advise the Sponsor to continue, redesign, or stop the study. 
13.6 Study Stopping Rules 
The Sponsor may terminate the study at any study site, at any time, for any of the following 
reasons: 
 Non-compliance to Good Clinical Practice (GCP) or protocol 
 Failure to enroll subjects 
 Major protocol deviations 
 Inaccurate or incomplete data 
 Unsafe or unethical practices 
 Safety or performance considerations 
 Recommendation made by the DSMB 
 Administrative decision 
13.7 Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
study site. Safety monitoring will include careful assessment and appropriate reporting of 
AEs. Medical monitoring will include a regular assessment of the number and type of SAEs. 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 52 of 101 
Document Date: 27OCT2016; Version 4.0 
13.8 Assessment of Risks and Benefits 
Any surgical procedure poses a potential risk, and the procedures undertaken as part of this 
study are no exception. There are always risks associated with any surgery or treatment and 
associated anesthesia, including death.  
 
These risks have been minimized by establishing strict inclusion/exclusion criteria to assure 
only appropriate surgical candidates participate in the study.  A diagnostic arthroscopy will be 
used to confirm that all inclusion criteria are met.   In addition, only trained surgeons with 
expertise in radio-frequency based debridement and expertise in performing an arthroscopic 
chondral lesion debridement plus partial medial meniscectomy will participate in this study.   
 
Participation in this study will not subject study participants to any additional risk other than 
that expected for other arthroscopic surgical procedures used to treat chondral defects. All 
study participants may benefit from having frequent physician visits and close observation.   
Additionally, the results of this investigation may benefit both physicians treating subjects 
and subjects diagnosed with a chondral lesion and meniscal defects by generating data 
regarding the safety and outcome of the procedure.  
 
Subjects will be advised of the potential risks and benefits associated with this study in the 
IRB approved ICF. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 53 of 101 
Document Date: 27OCT2016; Version 4.0 
13.8.1 Risks of Procedure 
Possible risks that may occur post-operatively with an arthroscopic treatment of a single 
medial femoral chondral lesion plus partial medial meniscectomy procedure are defined 
as follows: 
 Joint effusion 
 Hematoma 
 Adhesions or arthrofibrosis 
 Hemarthrosis 
 Reduced range of motion or gait status abnormality (temporary) 
 Localized pain 
 Sensation decrease at incision site 
 Inflammation 
 Infection 
 Chondrolysis 
 Fever 
 Synovitis 
 Deep Vein Thrombosis 
 Treatment failure due to rehabilitation non-compliance 
 Swelling and bruising 
 Fracture  
 Nerve injury 
 Tendon Injury 
 Delayed wound healing 
 Vascular injury 
 Conversion to mini-open or open procedure 
 Secondary surgical intervention to address complications associated with surgery 
or treatment 
 General risks associated with surgery and anesthesia                                                                         

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 54 of 101 
Document Date: 27OCT2016; Version 4.0 
13.8.2 Risks of Study Device 
Anticipated study device-related risks are identified below: 
 Prolonged surgery time due to device breakage or malfunction 
 Patient burn 
 Inadvertent ablation 
 
13.8.3 Benefits of Study Device 
Potential benefits of the study device include: 
 Minimal thermal penetration 
 Precise and efficient tissue removal 
 T2 (Temperature Technology) - facilities optimal performance by providing real-
time visual indicator when the temperature exceeds the recommended 50ºC 
(indicator transitions from blue to white) 
 
Ambient feature - provides accurate (±3°C) real-time temperature monitoring of the intra-
articular irrigating fluid 
 
14. DATA HANDLING AND RECORD KEEPING 
14.1 Confidentiality  
All information and data concerning subjects or their participation in this study will be 
considered confidential and handled in compliance with the ICH E6 and all applicable 
regulations. Only authorized personnel, the Sponsor or its designee, and applicable regulatory 
bodies will have access to these confidential files. All data used in the analysis, reporting, 
and publication of this study will be maintained without identifiable reference to the subject.  
 
The HIPAA (Health Insurance Portability and Accountability Act) Authorization adds to 
protections already provided by the elements of ICF and may be contained within the ICF 
document or as a separate document. The HIPAA document informs the subject that they can 
withdraw authorization to use data or samples not already submitted to the Sponsor or its 
designee and that the request must be in writing. If the subject allows samples to be used 
after withdrawal from the study, this permission may be withdrawn at a later date. The 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 55 of 101 
Document Date: 27OCT2016; Version 4.0 
HIPAA authorization specifies who may review confidential medical information and to 
whom test results will be submitted. It also describes that test results obtained solely for 
research will not be part of a subject’s medical record. 
 
In the event that a subject revokes authorization to collect or use personal health information, 
the Investigator, by regulation, retains the ability to use all information collected prior to the 
revocation of subject authorization. For subjects that have revoked authorization to collect or 
use personal health information, attempts should be made to obtain permission to collect at 
least vital status (i.e., that the subject is alive) at the end of their scheduled study period. 
14.2 Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a study necessary for the reconstruction and evaluation of the study. Source data 
are contained in source documents. Examples of source documents include, but are not 
limited to:  hospital records, clinical and office charts, laboratory notes, memoranda, 
subject’s diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate 
and complete, subject files, and records kept at the pharmacy, laboratories, and medico-
technical departments involved in the study. 
 
The following data may be recorded directly in the CRF, which will then be considered as 
source data:  
 IKDC Subjective Knee Evaluation Form 
 IKDC Knee Examination Form 
 KOOS 
 VAS, knee pain 
 SF-12 
 EQ-5D-5L 
 Subject Satisfaction Form 
 Physical Assessment - Knee 
 Imaging observations 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 56 of 101 
Document Date: 27OCT2016; Version 4.0 
 
14.3 Case Report Forms 
The CRF is an integral part of the study and subsequent reports. The CRF provided by the 
Sponsor must be used to capture all study data recorded in the subject’s medical record. The 
CRF must be kept current to reflect subject status during the course of the study. Only a 
subject screening number will be used to identify the subject. The Investigator must keep a 
separate log of subject names and medical record numbers (or other personal identifiers).  
 
After obtaining written source document information from each subject at each visit, the 
study site will enter the data into the CRF (paper or electronic). The monitor is responsible 
for performing on-site monitoring at regular intervals throughout the study to verify 
adherence to the protocol and local regulations on the conduct of clinical research as well as 
to ensure completeness, accuracy, and consistency of the data entered in the CRF.  
 
At the study site, the monitor must have access to subject medical records, study-related 
records, and written source documentation needed to verify the entries on the CRFs. Final 
monitored and/or audited CRFs will be available at all times, unless specified in writing to 
the Sponsor. These CRFs must be reviewed and verified for accuracy by the Principal 
Investigator and signed off (via electronic and/or paper signature). A copy of the final CRFs 
will remain at the Investigator’s study site at the completion of the study. 
 
Pharmacoeconomic data relating to the surgery (i.e., operating room time, surgical time, 
blood loss), length of stay, admission, discharge, return to normal activities, medications, 
research center visits, and other related intervention and procedural costs and billing 
information may be collected when available for each group (study and control).  
14.4 Data Management 
Data management and handling will be conducted according to the study specific Data 
Management Plan in accordance with applicable guidelines.  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 57 of 101 
Document Date: 27OCT2016; Version 4.0 
14.5 Records Retention 
Investigators are required to maintain all study documentation, including CRFs, ICFs, and 
adequate records for the receipt and disposition of the study according to the regulatory 
requirements and/or until notified by the Sponsor that the records may be destroyed. If the 
Principal Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept responsibility. The Sponsor must be notified in writing of the name and address of the 
new custodian.  
 
15. STUDY MONITORING, AUDITING, AND INSPECTING 
A monitor, whether an employee of the Sponsor or its designee, has the obligation to follow this 
study closely. In doing so, the monitor will visit the study sites at periodic intervals, in addition 
to maintaining necessary contact. The monitor will maintain current personal knowledge of the 
study through observation, review of study records and source documentation, and discussion of 
the conduct of the study with the Investigator and staff. Quality assurance auditors, whether an 
employee of the Sponsor or its designee, may evaluate study conduct at the study sites. These 
parties must have access to any and all study reports and source documentation, regardless of 
location and format. The Sponsor audit reports will be kept highly confidential.  
 
15.1 Study Monitoring 
Monitoring of study progress and conduct will be ongoing. The study will be monitored 
throughout its active phase. The first monitoring visit during the active phase of the study 
will occur shortly after the first subject has been enrolled into the study at any particular 
study site. Subsequent monitor visits will occur as the frequency of enrollment dictates. 
 
The Investigator will allocate adequate time for such monitoring activities. The Investigator 
will also ensure that the monitor or other compliance or quality assurance reviewer is given 
access to all the above noted study-related documents and study-related facilities (e.g., 
pharmacy, operating room, etc) and has adequate space to conduct the monitoring visit. All 
data recorded during the study will be available for audit against source data and for 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 58 of 101 
Document Date: 27OCT2016; Version 4.0 
compliance with GCP (21 CFR Parts 11, 50, 54, 56, 812, ICH E6) and specific protocol 
requirements. The Principal Investigator will be responsible for the following: 
 Monitoring study conduct to ensure that the rights and well-being of subjects are 
protected; 
 Monitoring accuracy, completion, and verification of source documents; and 
 Monitoring study conduct to ensure study compliance with the 
protocol/amendment(s), GCP, and applicable regulatory requirements.  
 
15.2 Auditing and Inspecting 
The Investigator will permit study-related monitoring, audits, and inspections by the 
IRB/REB, the Sponsor, government regulatory bodies, and institution compliance and quality 
assurance groups of all study-related documents (e.g., source documents, regulatory 
documents, data collection instruments, study data, etc). The Investigator will ensure the 
capability for inspections of applicable study-related facilities (e.g., pharmacy, operating 
room, etc). 
Participation as an Investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable institution compliance and quality 
assurance offices. 
 
16. ETHICAL CONSIDERATIONS 
This study will be conducted according to the protocol, the US Code of Federal Regulations 21 
CFR Part 50, 54, 56, and 812, the ethical principles of GCP as defined in ICH E6, and the ICH 
Guidelines. All aspects of this study will be conducted in accordance with all national, state, and 
local laws of the pertinent regulatory authorities.  
The decision of the IRB/REB concerning the conduct of the study will be made in writing to the 
Investigator and a copy of this decision will be provided to the Sponsor before commencement 
of this study. The Investigator should provide a list of IRB/REB members or an IRB/REB 
assurance number to the Sponsor.  
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 59 of 101 
Document Date: 27OCT2016; Version 4.0 
16.1 Protocol Amendments 
All protocol amendments must be submitted to the IRB/REB and regulatory authorities, as 
required. A protocol amendment is generated by the Sponsor. The Investigator(s) is notified 
of the changes. The amended and/or revised protocol cannot be implemented until IRB/REB 
approval is received, as required. Protocol revisions that impact on subject safety, the scope 
of the study, or affect the scientific quality of the study must be approved by the IRB/REB 
and submitted to the regulatory authorities, as required, before implementation of such 
revisions to the conduct of the study.   
 
The Sponsor may, at any time, amend this protocol to eliminate an apparent immediate 
hazard to a subject. In this case, the appropriate regulatory authorities will be subsequently 
notified.  In the event of a protocol revision, the ICF may require revisions, which must also 
be approved by the IRB/REB. 
 
16.2 Informed Consent 
All subjects for this study will be provided an IRB/REB approved ICF describing this study 
and providing sufficient information for subjects to make an informed decision about 
participation in this study. This consent form will be submitted with the protocol for review 
and approval by the IRB/REB for the study. The formal consent of a subject, using the 
IRB/REB approved ICF, must be obtained prior to any study participation. The consent form 
must be signed by the subject and the Investigator and/or designated research professional 
obtaining the consent. A copy of the signed and dated ICF must be given to the subject, and 
the consent process must be documented in the source documentation. Before recruitment 
and enrollment, each prospective subject will be given a full explanation of the study, 
allowed to read the approved ICF, and be provided with ample time and the opportunity to 
ask any questions that may arise. Once all questions have been answered and the Investigator 
is assured that the subject understands the implications of participating in the study, the 
subject will be asked to give consent to participate in the study by signing the ICF. As part of 
the consent process, each subject must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/REB review, and regulatory inspection. If an 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 60 of 101 
Document Date: 27OCT2016; Version 4.0 
amendment to the protocol changes the subject participation schedule or activity or increases 
the potential risk to the subject, the ICF must be revised and submitted to the IRB/REB for 
review and approval. The revised ICF must be used to obtain consent from a subject 
currently enrolled in the study if he/she is affected by the amendment, as deemed necessary 
by the reviewing IRB/REB. The revised ICF must be used to obtain consent from any new 
subjects who are enrolled into the study after the date of the IRB/REB approval. 
 
17. INVESTIGATOR TRAINING 
17.1 Investigator Training 
The Sponsor will select only Investigator(s) with extensive experience in performing 
arthroscopic knee procedures. Training on the protocol will be provided prior to the start of 
the study. The protocol will be reviewed with the Investigator(s) and their study personnel at 
the Site Initiation Visit. In addition, all Investigators will be required to perform 1 to 3 
procedures using the Quantum 2 Controller plus Paragon T2 ICW Wand or the WEREWOLF 
Controller plus FLOW 50 Wand (Part I).  The purpose of these procedures will be will be to 
minimize variability relating to the technique recommended in the IFU.  These subjects will 
be followed per protocol and analyzed for safety findings only. 
 
17.2 Training of Staff 
The Investigator will ensure that appropriate training relevant to the study is given to the 
medical, nursing and other staff involved and that new information of relevance to the 
performance of this study is forwarded to the staff involved. 
 
18. PUBLICATION PLAN 
Authorship and contents of the publication shall be discussed between each Principal 
Investigator at the study centers participating in this study and the Sponsor.  The Sponsor shall 
serve as the coordinator of multi-center study disclosures and, in the event of a disagreement 
among the investigators, the Sponsor shall determine, in its sole discretion, the resolution of any 
such dispute.  The Sponsor shall be furnished copies of any proposed multi-center publication or 
disclosure, including, without limitation, disclosures in papers or abstracts or at research 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 61 of 101 
Document Date: 27OCT2016; Version 4.0 
seminars, lectures, professional meetings, or poster sessions, at least 90 days prior to the 
proposed date for submission for publication or disclosure.  During such 90-day period, the 
Sponsor shall have the right to review and require modification of such publication to assure the 
accuracy of the contents thereof and to delete Sponsor Confidential Information therefrom.  In 
addition, upon the Sponsor’s written request during the foregoing 90-day period, the proposed 
submission for publication or disclosure shall be delayed for a period not to exceed ninety (90) 
days from the date of such request to permit the Sponsor to file patent applications or to 
otherwise seek intellectual property protection related to information contained in such 
publication or disclosure.   
 
It is also agreed that no presentations or publications will be authorized individually or by 
subgroups participating in the Study without the consent of the Sponsor prior to publication of 
the pooled data; provided however that in no event shall any Institution or Investigator involved 
in this Study be restricted from submitting a publication independently after the expiration of 365 
days from the completion of the multi-center study. 
 
19. INSTITUTIONAL REVIEW BOARD / RESEARCH ETHICS BOARD 
Before initiation of the study, the Investigator must obtain approval of the protocol, ICF, CRFs, 
and any advertisement for subject recruitment from an IRB/REB complying with the provisions 
specified in 21 CFR Part 56 or ICH GCP, as applicable, and pertinent government regulations.   
 
A copy of written IRB/REB approvals of the protocol, ICF, CRFs, and any advertising for 
subject recruitment (if applicable) must be provided to the Sponsor or its designee prior to 
initiation of the study. The approval letter must be signed by the IRB/REB chairman or designee, 
identify the IRB/REB name and address, identify the protocol by title and/or protocol number, 
and include the date that approval was granted. The letter must also contain a statement that the 
IRB/REB complies with the requirements in 21 CFR Part 56 for a study conducted under ICH or 
GCP, as applicable. 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 62 of 101 
Document Date: 27OCT2016; Version 4.0 
The Investigator is responsible for obtaining continued review of the clinical research or 
submitting periodic progress reports, in accordance with applicable regulations, at intervals not 
exceeding one year or otherwise specified by the IRB/REB. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 63 of 101 
Document Date: 27OCT2016; Version 4.0 
20. REFERENCES 
 
1. Figueroa D, Calvo R, Vaisman A, Carrasco MA, Moraga C, Delgado I. Knee 
chondral lesions: incidence and correlation between arthroscopic and magnetic 
resonance findings. Arthroscopy 2007; 23(3):312-315. 
2. Hjelle K, Solheim E, Strand T, Muri R, Brittberg M. Articular cartilage defects in 
1,000 knee arthroscopies. Arthroscopy 2002; 18(7):730-734. 
3. Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 
25,124 knee arthroscopies. Knee 2007; 14(3):177-182. 
4. Sgaglione NA, Miniaci A, Gillogly SD, Carter TR. Update on advanced surgical 
techniques in the treatment of traumatic focal articular cartilage lesions in the knee. 
Arthroscopy 2002; 18(2 Suppl 1):9-32. 
5. Brittberg M, Winalski CS. Evaluation of cartilage injuries and repair. J Bone Joint 
Surg Am 2003; 85-A Suppl 2:58-69. 
6. Voloshin I, Morse KR, Allred CD, Bissell SA, Maloney MD, DeHaven KE. 
Arthroscopic evaluation of radiofrequency chondroplasty of the knee. Am J Sports 
Med 2007; 35(10):1702-1707. 
7. Owens BD, Stickles BJ, Balikian P, Busconi BD. Prospective analysis of 
radiofrequency versus mechanical debridement of isolated patellar chondral lesions. 
Arthroscopy 2002; 18(2):151-155. 
8. Barber FA, Iwasko NG. Treatment of grade III femoral chondral lesions: mechanical 
chondroplasty versus monopolar radiofrequency probe. Arthroscopy 2006; 
22(12):1312-1317. 
9. Spahn G, Klinger HM, Mückley T, Hofmann GO. Four-year results from a 
randomized controlled study of knee chondroplasty with concomitant medial 
meniscectomy: mechanical debridement versus radiofrequency chondroplasty. 
Arthroscopy 2010; 26(9 Suppl):S73-80. 
10. Roos M. Ewa, Lohamander Stephan L, The Knee injury and Osteoarthritis Outcome 
Score (KOOS): from joint injury to osteoarthritis. BioMed Central 2003; 1:64, page 5 
of 8 
11. Chen JYH, Demets DL, and Lan KKG ‘ Increasing the Sample Size when unblinded 
interim results is promising,’ Statistics in Medicine 23 (2004) 1023- 1038. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 64 of 101 
Document Date: 27OCT2016; Version 4.0 
 
21. APPENDICIES  
21.1 Appendix A - Draft Informed Consent 
 
21.1.1 US Sites- Draft Informed Consent 
 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Title:               A Prospective, Double Blinded, Multi-Center, Randomized, Controlled Trial to 
Evaluate Mechanical Debridement vs. Radiofrequency-Based Debridement in the 
treatment of Articular Cartilage Lesions 
  
 
 
Protocol No.:              SM-2012-02 
 
 
Investigator:  
 
 
Sub-Investigator(s): 
 
 
 
 
Sponsor:                       Smith & Nephew, Inc.  
1450 E. Brooks Road  
Memphis, TN 38116  
US     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 65 of 101 
Document Date: 27OCT2016; Version 4.0 
 
    Introduction:  Before agreeing to participate in this research study, it is important that you 
read and understand this consent form. This form provides all the information we think you will 
need to know in order to decide whether you wish to participate in the study. If you have any 
questions after you read through this form, ask your questions to the study doctor or study 
personnel. You should not sign this form until you are sure you understand everything on this 
form. You may also wish to discuss your participation in this study with your family doctor, a 
family member, or a close friend. It is required that you sign this consent form before the study 
doctor or study personnel can begin any study procedures. 
 
It is important that you answer any questions, to the best of your ability, which your study doctor 
may ask with respect to your health history and any medications you may be taking. This is done 
in order to prevent any unnecessary harms to you should you decide to participate in this study. 
 
 
 
    Purpose of the Study:  You are being asked to participate in this research study because 
you require an arthroscopic knee procedure for the treatment of a chondral lesion and torn 
meniscus. This study will evaluate 2 different treatments, Mechanical Debridement (i.e., a 
mechanical shaver that removes areas of damaged tissue) and Radiofrequency Debridement (i.e., 
electrical energy that removes areas of damaged tissue), used to repair the chondral lesion in 
your knee. Your torn meniscus will be treated per standard of care by your study doctor. 
 
All of the Mechanical Debridement and Radiofrequency Debridement devices being used in this 
study have obtained clearance by the U.S. Food and Drug Administration (FDA) for commercial 
use and are currently being used on the market.  
 
The study doctor would normally use any one of the methods, Mechanical Debridement or 
Radiofrequency Debridement, to treat your knee, but right now it is not known if one of these 
methods is better than the other. This study is being conducted to see whether Radiofrequency 
Debridement is as safe and effective as Mechanical Debridement in patients with knee problems 
such as yours.  
 
This study will involve up to 3 Part 1 patients per study doctor and a total of 82 Part 2 patients 18 
years of age and over, who will participate in this study at up to 13 medical centers across the 
United States and Canada.  
 
  Study Device Description:  The Quantum™ 2 Controller plus Paragon T2™ ICW and the 
WEREWOLF™ Controller plus FLOW 50™ Wand are device systems manufactured by ArthroCare 
and distributed by Smith & Nephew. Both systems are designed for use in 
orthopaedic/arthroscopic surgical procedures. These devices will be used to perform the 
Radiofrequency Debridement.  
 
The study devices use electrical energy to precisely dissolve (remove) damaged tissue at 
relatively low temperatures (typically 40°C to 70°C). 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 66 of 101 
Document Date: 27OCT2016; Version 4.0 
 Description of the Study:   If you are enrolled in the study, your participation will last 104 
weeks (2 years). You will have to visit the study site a total of 9 times during the study, including 
the time you come in for your surgery. 
 
The study will be conducted in two (2) parts: 
 
 Every study doctor is required to complete 1 to 3 Part 1 subjects. If you are included in 
Part 1 of the study, you will be treated with one of the Radiofrequency Debridement 
devices. The information collected will be evaluated for safety of the study device. 
 Part 2 will include an additional 82 subjects who will be assigned to one of two groups 
in order to compare the treatments. These groups are selected by chance, as if by tossing 
a coin. You have one in two chances of being placed into one of the following treatment 
groups: 
 
o Mechanical Debridement, or 
o Radiofrequency Debridement (study devices)  
 
The information collected in Part 2 will be evaluated for safety and effectiveness of the 
study device. If you are included in Part 2 of the study, you will not know what group 
you have been assigned to and therefore what treatment you received until 104 weeks (2 
years) after your surgery, at the end of the study. 
 
Visit 1:  If you choose to participate in this study, you will be evaluated to determine if you are a 
good candidate for the study. The study personnel will perform the following procedures to find 
out if you qualify for the study: 
 
 Ask general questions about your health and current medications 
 Perform a knee assessment 
 Have you complete study questionnaires regarding your pain, function, and general 
health  
 
If you fulfill all criteria for the study, you will be assigned for surgery. 
 
Visit 2 – Surgery:  During surgery, the following will take place: 
 
 You will be administered standard anesthesia 
 The study doctor will make several small incisions in your knee in order to perform the 
arthroscopic surgery 
 After your torn meniscus is treated, the study treatment portion will begin and you will 
receive the assigned treatment 
 The areas of incision will be closed 
 
Immediately following surgery, you will have a bandage and dressing on your treated knee. You 
may be given a prescription for pain medication to use if you have pain following the surgery. 
You may also be prescribed a standard physical therapy regimen. These are the same procedures 
used for any knee surgery. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 67 of 101 
Document Date: 27OCT2016; Version 4.0 
 
If, during the surgery, your study doctor determines that your condition no longer meets the 
requirements for the study you will not be able to complete the study. In this case, you will not 
be asked to undergo additional study visits and will be treated according to the standard of care 
normally given by your doctor for your condition. 
 
The study personnel will explain the pre-surgical and surgical procedures to you in greater detail 
and answer any questions you have.  
 
Visits 3 – 9:  You will see your study doctor for follow-up after surgery at day 10 (Visit 3), 6 
weeks (Visit 4), 12 weeks (Visit 5), 24 weeks (Visit 6), 36 weeks (Visit 7), 52 weeks (Visit 8), 
and 104 weeks (Visit 9). At each follow-up visit, you will be asked general questions about your 
health and will complete study questionnaires regarding your pain, function, and general health. 
You will be free to decline answering any questions that you do not feel comfortable answering. 
It is anticipated that the questionnaires will take 20 minutes to complete at each visit. 
 
At Visits 4, 5, 6, 7, 8, and 9 the study personnel will perform a knee assessment, which will take 
up to 10 minutes to complete. 
 
At Visits 3, 8, and 9, a MRI will be taken of your treated knee. An MRI is a magnetic resonance 
image that will show the interior area of your knee following surgery. It is anticipated that the 
MRI will take up to 1 hour to complete at each of these visits. Your MRIs may be re-evaluated at 
a later date. 
 
In total, there are 5 extra visits that are not standard follow-up for this type of procedure (i.e. 
Visits 5, 6, 7, 8, and 9). MRIs are not usually taken at any follow-up visits for arthroscopic knee 
procedures. In addition, questionnaires may not be completed as standard follow-up. These extra 
visits and procedures are being done in this study to provide additional information on the safety 
and effectiveness of Radiofrequency Debridement. 
 
Pharmacoeconomic data such as information relating to the surgery (i.e., operating room time, 
procedures performed), work status, medications, study site visits, rehabilitation and other 
related treatment and procedural costs and billing information may be collected when available 
for each treatment group (Mechanical Debridement and Radiofrequency Debridement).  
 
   Potential Harms (Injury, Discomforts, or Inconvenience):  As with any arthroscopic knee 
surgery involving anesthesia there are potential risks and complications, including:  dizziness, 
fainting, difficulty breathing, fluid buildup on knee (joint effusion), bruising of soft tissue  
(hematoma), scar tissue (adhesions), painful restriction of joint motion (arthrofibrosis), bleeding 
into the knee joint (hemarthrosis), reduced range of motion or abnormal walking (gait status 
abnormality) (temporary), localized pain, sensation decrease at incision site, inflammation of 
knee, infection, breakdown of articular cartilage (chondrolysis), fever, inflammation of the knee 
joint (synovitis), deep vein blood clot (deep vein thrombosis), treatment failure due to 
rehabilitation non-compliance, swelling of the knee, bruising of the knee, break in bone 
(fracture), nerve injury, tendon injury, delayed wound healing, vascular injury, conversion to 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 68 of 101 
Document Date: 27OCT2016; Version 4.0 
mini-open or open procedure vs. arthroscopic procedure and/or additional surgery to fix 
problems associated with the first surgery. 
 
 
The potential medical risks associated with the study device are prolonged surgery time due to 
device breakage or malfunction, patient burn, and/or inadvertent tissue removal.  
 
Your study doctor is experienced in this type of surgery, but the results of this surgery cannot be 
guaranteed. It is possible that the surgery will not reduce the pain or disability felt before 
surgery. In addition, the pain or disability may be worse after the surgery. It is possible that by 
being in the study, you can have problems and/or side effects not know at this time. There is 
some element of this risk in all surgeries, whether or not you receive the study device.  
 
If you choose to take part in this study, you will be informed of any significant new findings 
(either good or bad), such as changes in the risks or benefits resulting from participation in the 
study, that might cause you to change your mind about continuing in the study. You may be 
asked to sign a new consent form if this occurs.  
 
Participating in more than one study may increase risks to you and may affect study results. You 
should tell your study doctor if you are considering joining another study. 
 
   Women as Study Subjects:  If you are a woman and are pregnant you cannot be in this 
study. If a woman is pregnant or nursing a child when she has medication associated with 
surgery there may be risks to the unborn baby or nursing child. 
 
If you think that you are pregnant during the study, you must tell the study doctor immediately. 
If you become pregnant before the surgery, you will be removed from the study.  
 
   Potential Benefits:  You may not benefit directly from participating in this study. If you 
choose to participate in the study, your condition may or may not improve. The potential benefits 
of the study device are minimal thermal penetration and precise and efficient tissue removal. The 
information collected in this study to determine the safety and effectiveness of Radiofrequency 
Debridement may benefit future patients undergoing arthroscopic knee surgery.  
 
   Treatment Options:  If you choose not to participate in this study, there are other treatments 
available to you. These include receiving the treatment that is routinely offered by this 
clinic/hospital for a chondral lesion and torn meniscus or not have any treatment at all. These 
alternatives may have similar and/or additional risks and precautions. Your doctor will have 
additional information on the alternative treatments.  
 
If you choose to participate in this study, you will be asked not to have another surgical treatment 
for your knee, unless you have recurring or new pain and/or symptoms, until the 104th week (2 
year) visit is complete.  
 
   Confidentiality and Privacy:   All persons associated with this study, including study 
doctors, coordinators, nurses and delegates (hereby referred to as “study personnel”) and the 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 69 of 101 
Document Date: 27OCT2016; Version 4.0 
sponsor (Smith & Nephew) or its designee are committed to respecting your privacy. No other 
persons will have access to your personal health information or other identifying personal 
information without your consent, unless required by law.   
 
The study information collected will be part of what is called your “personal health information” 
and is identifying information about you that relates to your health or the provision of health care 
services to you. Your personal health information will include the information from the 
procedures described in this consent form, as well as other information about you, such as your 
name and address.  
 
Any personal health information collected or other information related to you will be coded by 
screening numbers to ensure that persons outside of the study will not be able to identify you. 
The study personnel are in control of the screening number code key, which is needed to connect 
your personal health information to you. Our guidelines include the following: 
 
 All information that identifies you, both paper copy and electronic information, will be 
kept confidential and stored and locked in a secure place that only the study personnel 
will be able to access.  
 Electronic files will be stored securely on hospital or institutional networks or securely 
on any portable electronic devices. 
 No information identifying you will be allowed off site in any form. Examples include 
your hospital or clinic charts, copies of any part of your charts, or notes made from your 
charts. 
 
It is important to understand that despite these protections being in place, there continues to be 
the risk of unintentional release of information. The study personnel will protect your records 
and keep all the information in your study file confidential to the greatest extent possible. The 
chance that this information will be accidentally released is small. 
 
By signing this form, you are authorizing access to your medical records by the study personnel, 
authorized representatives (i.e., study monitor) of the sponsoring company, the Institutional 
Review Board (IRB), and by government regulatory authorities (i.e., the US Food and Drug 
Administration (FDA), the Department of Health and Human Services, and/or regulatory 
agencies from other countries). This authorization does not have an expiration date. Such access 
will be used for the purpose of verifying the authenticity and accuracy of the information 
collected for the study and for checking patient safety, without violating your confidentiality to 
the extent permitted by applicable laws and regulations.  
 
Federal regulations, including the Health Insurance Portability and Accountability Act (HIPPA) 
protect your personal information. They also give you the right to control the use of your 
personal information (including personal health information) and require your written permission 
for this personal information to be collected, used, or disclosed for the purposes of this study, as 
described in this consent form. You have the right to review and copy your personal information 
collected in this study. However, if you decide to be in this study or choose to withdraw from it, 
your right to look at or copy your personal information related to this study will be delayed until 
after the research study is completed.  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 70 of 101 
Document Date: 27OCT2016; Version 4.0 
 
Photographs may be taken of your knee before, during, and after the surgery; however, your 
identity will not be revealed. 
 
By FDA regulations, the study sites and the sponsor will keep your study records for at least 2 
years from the conclusion of the study. Your study records will then be destroyed in a secure 
manner once the retention period has elapsed.  
 
A description of this research study will be available on http://www.ClinicalTrials.gov, as 
required by US Law. This web site will not include information that can identify you. At most, 
the web site will include a summary of the results. You can search this web site at any time. 
 
   Study Results: The results of this study may be presented at conferences, seminars or other 
public forums, and published in journals, but at no time will you be identified. No information 
will be used in these presentations that would disclose your identity as a study subject. The 
analyzed data may also be used to plan for future research studies or to prepare reports or 
marketing applications to regulatory agencies. 
 
   Participation and Withdrawal:  Participation in any research study is voluntary. If you 
choose not to participate, you and your family will continue to have access to customary care at 
this study site. If you decide to participate in this study you can change your mind without giving 
a reason, and you may withdraw from the study at any time without any effect on the care you 
and your family will receive at this study site. If you decide to withdraw your consent to 
participate in this study, you must write a letter to the study doctor.  
 
The sponsor, the study doctor, the FDA, or the IRB may withdraw you from the study without 
your consent under the following circumstances:  
 
 
to protect your health and safety,  
 
failure to comply with study procedures,  
 
failure to later consent to any changes made in the study plan, or 
   the study is terminated for any reason. 
 
If you withdraw from the study, the data collected for you up to that time will be used to 
maintain the integrity of the study, but no more data on you will be collected. You will also be 
asked to return for a final visit for safety concerns and standard clinical care.  
 
 Cost:  All costs that are part of your usual medical care, such as your surgery and physical 
therapy will be charged to your insurance company if you have such coverage. You will be 
responsible for all costs that are not paid by your insurance company. You should check with 
your insurance company before you enroll in this study. If you have no health insurance you will 
be held responsible for paying all costs of the study. 
 
Costs which are not associated with standard treatment, such as costs of MRI required 
specifically for this research study, will be paid for by the sponsor.   
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 71 of 101 
Document Date: 27OCT2016; Version 4.0 
While you are in the study, you may still need to get regular medical care. You will still have to 
pay for the costs of your regular medical care that are not a part of this study. To find out more 
about costs, you can ask the study doctor or study personnel.  
 
 Compensation for Injury:  In no way does signing this form waive your legal rights nor 
release the study doctor(s), the study personnel, the sponsor (Smith & Nephew) or this study site 
from their legal and professional responsibilities.  
 
If you experience an injury or illness during the course of the study, you should seek medical 
treatment from a doctor, or treatment center of your choice, and promptly notify your study 
doctor.   
 
In the event that any illness or injury is determined to be related to the study procedure, your 
study doctor will provide essential medical treatment. You will not be charged for reasonable 
medical expenses required to treat the injury or illness if your study doctor has determined that 
the injury or illness is directly related to the study procedure and is not the result of a pre-existing 
condition caused by accidental re-injury or because you have not followed your study doctor's 
directions.    
 
If you have any questions about this, please ask the study doctor or study personnel. 
 
  Potential Costs/Reimbursements:  You will be compensated $60 (per visit) for Visits 1, 4, 
5, 6, and 7 and $100 (per visit) for Visits 3, 8, and 9 that you complete. This will total $600 over 
the course of the study and is to compensate you for your time and any travel expenses 
associated with your participation in this research study. 
 
  Source of Funding for the Study:  Funding for this research study will be provided by the 
sponsor (Smith & Nephew).  
 
  Institutional Review Board Contact:  If you have any questions regarding your rights as a 
research subject in this study, you may contact name at xxx-xxx-xxxx. 
 
  Consent:  This consent form is only part of the process of informed consent. It should give 
you the basic idea of what the research study is about and what your participation will involve. It 
is not consent for surgery. You will be asked to sign a separate consent form for surgery. Your 
continued participation should be as informed as this initial consent so you should feel free to ask 
for clarification or new information throughout your participation in the study.  
 
 
 
 
 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 72 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
 
 
A Prospective, Double Blinded, Multi-Center, Randomized, Controlled Trial to Evaluate 
Mechanical Debridement vs. Radiofrequency-Based Debridement in the treatment of Articular 
Cartilage Lesions 
 
I acknowledge that the research study described above has been explained to me and that any questions 
that I have asked have been answered to my satisfaction. I have been informed of the alternatives to 
participation in this study, including the right not to participate and the right to withdraw without 
compromising the quality of medical care at this study site for me and for other members of my family. 
As well, the potential risks, harms, and discomforts have been explained to me, and I also understand the 
benefits of participating in the research study. 
 
I understand that I have not waived my legal rights nor released the study doctors, or involved 
institutions, from their legal and professional duties. I know that I may ask now, or in the future, any 
questions that I have about the study or the research procedures. I have been assured that those records 
relating to me, and my care, will be kept confidential and that no information will be released or printed 
that would disclose personal identity without my permission unless required by law. I have been given 
sufficient time to read and understand the above information. 
 
I hereby freely and voluntarily consent to participate, and I will be given a signed copy of this consent 
form.  
 
_____________________________________ 
Name of Subject (please print) 
 
_____________________________________                  ________________________ 
Signature of Subject           
 
 
 
  Date  
 
 
 
 
 
 
________________________________  
 
Name/Status of Individual obtaining Consent (please print) 
 
 
 
_____________________________________                  ________________________ 
Signature of Individual obtaining Consent  
              Date 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 73 of 101 
Document Date: 27OCT2016; Version 4.0 
21.1.2 Canadian Site- Draft Informed Consent 
 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Title:                A Prospective, Double Blinded, Multi-Center, Randomized, Controlled Trial to 
Evaluate Mechanical Debridement vs. Radiofrequency-Based Debridement in the 
treatment of Articular Cartilage Lesions 
 
 
 
Protocol No.:              SM-2012-02 
 
 
Investigator:  
 
 
Sub-Investigator(s): 
 
 
 
 
Sponsor:                          Smith & Nephew, Inc.  
1450 E. Brooks Road  
Memphis, TN 38116  
US     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 74 of 101 
Document Date: 27OCT2016; Version 4.0 
    Introduction:  Before agreeing to participate in this research study, it is important that you 
read and understand this consent form. This form provides all the information we think you will 
need to know in order to decide whether you wish to participate in the study. If you have any 
questions after you read through this form, ask your questions to the study doctor or study 
personnel. You should not sign this form until you are sure you understand everything on this 
form. You may also wish to discuss your participation in this study with your family doctor, a 
family member, or a close friend. It is required that you sign this consent form before the study 
doctor or study personnel can begin any study procedures.  
 
It is important that you answer any questions, to the best of your ability, which your study doctor 
may ask with respect to your health history and any medications you may be taking. This is done 
in order to prevent any unnecessary harms to you should you decide to participate in this study. 
 
 
 
    Purpose of the Study:  You are being asked to participate in this research study because 
you require an arthroscopic knee procedure for the treatment of a chondral lesion and torn 
meniscus. This study will evaluate 2 different treatments, Mechanical Debridement (i.e., a 
mechanical shaver that removes areas of damaged tissue) and Radiofrequency Debridement (i.e., 
electrical energy that removes areas of damaged tissue), used to repair the chondral lesion in 
your knee. Your torn meniscus will be treated per standard of care by your study doctor. 
 
The Mechanical Debridement devices and the Radiofrequency Debridement device system 
Quantum™ 2 Controller plus Paragon T2™ ICW have obtained clearance by Health Canada (HC) 
for commercial use and are currently being used on the market. The Radiofrequency 
Debridement device system WEREWOLF™ Controller plus FLOW 50™ Wand has not obtained 
clearance by HC for commercial use. The WEREWOLF™ Controller plus FLOW 50™ Wand will 
only be used in medical centers in the United States and not in Canada.  
 
The study doctor would normally use any one of the methods, Mechanical Debridement or 
Radiofrequency Debridement, to treat your knee, but right now it is not known if one of these 
methods is better than the other. This study is being conducted to see whether Radiofrequency 
Debridement is as safe and effective as Mechanical Debridement in patients with knee problems 
such as yours.  
 
This study will involve up to 3 Part 1 patients per study doctor and a total of 82 Part 2 patients 18 
years of age and over, who will participate in this study at up to 13 medical centers across the 
United States and Canada.  
 
  Study Device Description:  The Quantum™ 2 Controller plus Paragon T2™ ICW and the 
WEREWOLF™ Controller plus FLOW 50™ Wand are device systems manufactured by ArthroCare 
and distributed by Smith & Nephew. Both systems are designed for use in 
orthopaedic/arthroscopic surgical procedures. The Quantum™ 2 Controller plus Paragon T2™ ICW 
device will be used at the Canadian sites to perform the Radiofrequency Debridement. 
 
The study devices use electrical energy to precisely dissolve (remove) damaged tissue at 
relatively low temperatures (typically 40°C to 70°C). 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 75 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
 Description of the Study:   If you are enrolled in the study, your participation will last 104 
weeks (2 years). You will have to visit the study site a total of 9 times during the study, including 
the time you come in for your surgery. 
 
The study will be conducted in two (2) parts: 
 
 Every study doctor is required to complete 1 to 3 Part 1 subjects. If you are included in 
Part 1 of the study, you will be treated with Radiofrequency Debridement. The 
information collected will be evaluated for safety of the study device. 
 Part 2 will include an additional 82 subjects who will be assigned to one of two groups 
in order to compare the treatments. These groups are selected by chance, as if by tossing 
a coin. You have one in two chances of being placed into one of the following treatment 
groups: 
 
o Mechanical Debridement, or 
o Radiofrequency Debridement (study device).  
 
The information collected in Part 2 will be evaluated for safety and effectiveness of the 
study device. If you are included in Part 2 of the study, you will not know what group 
you have been assigned to and therefore what treatment you received until 104 weeks (2 
years) after your surgery, at the end of the study. 
 
Visit 1:  If you choose to participate in this study, you will be evaluated to determine if you are a 
good candidate for the study. The study personnel will perform the following procedures to find 
out if you qualify for the study: 
 
 Ask general questions about your health and current medications 
 Perform a knee assessment 
 Have you complete study questionnaires regarding your pain, function, and general 
health  
 
If you fulfill all criteria for the study, you will be assigned for surgery. 
 
Visit 2 – Surgery:  During surgery, the following will take place: 
 
 You will be administered standard anesthesia 
 The study doctor will make several small incisions in your knee in order to perform the 
arthroscopic surgery 
 After your torn meniscus is treated, the study treatment portion will begin and you will 
receive the assigned treatment.  
 The areas of incision will be closed 
 
Immediately following surgery, you will have a bandage and dressing on your treated knee. You 
may be given a prescription for pain medication to use if you have pain following the surgery. 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 76 of 101 
Document Date: 27OCT2016; Version 4.0 
You may also be prescribed a standard physical therapy regimen. These are the same procedures 
used for any knee surgery. 
 
If, during the surgery, your study doctor determines that your condition no longer meets the 
requirements for the study you will not be able to complete the study. In this case, you will not 
be asked to undergo additional study visits and will be treated according to the standard of care 
normally given by your doctor for your condition. 
 
The study personnel will explain the pre-surgical and surgical procedures to you in greater detail 
and answer any questions you have.  
 
Visits 3 – 9:  You will see your study doctor for follow-up after surgery at 7-13 days (Visit 3), 6 
weeks (Visit 4), 12 weeks (Visit 5), 24 weeks (Visit 6), 36 weeks (Visit 7), 52 weeks (Visit 8), 
and 104 weeks (Visit 9). At each follow-up visit, you will be asked general questions about your 
health and will complete study questionnaires regarding your pain, function, and general health. 
You will be free to decline answering any questions that you do not feel comfortable answering. 
It is anticipated that the questionnaires will take 20 minutes to complete at each visit. 
 
At Visits 4, 5, 6, 7, 8, and 9 the study personnel will perform a knee assessment, which will take 
up to 10 minutes to complete. 
 
At Visits 3, 8, and 9, a MRI will be taken of your treated knee. An MRI is a magnetic resonance 
image that will show the interior area of your knee following surgery. It is anticipated that the 
MRI will take up to 1 hour to complete at each of these visits. Your MRIs may be re-evaluated at 
a later date. 
 
In total, there are 5 extra visits that are not standard follow-up for this type of procedure (i.e. 
Visits 5, 6, 7, 8, and 9). MRIs are not usually taken at any follow-up visits for arthroscopic knee 
procedures. In addition, questionnaires may not be completed as standard follow-up. These extra 
visits and procedures are being done in this study to provide additional information on the safety 
and effectiveness of Radiofrequency Debridement. 
 
Pharmacoeconomic data such as information relating to the surgery (i.e., operating room time, 
procedures performed), work status, medications, study site visits, rehabilitation and other 
related treatment and procedural costs and billing information may be collected when available 
for each treatment group (Mechanical Debridement and Radiofrequency Debridement).  
 
   Potential Harms (Injury, Discomforts, or Inconvenience):  As with any arthroscopic knee 
surgery involving anesthesia there are potential risks and complications, including:  dizziness, 
fainting, difficulty breathing, fluid buildup on knee (joint effusion), bruising of soft tissue  
(hematoma), scar tissue (adhesions), painful restriction of joint motion (arthrofibrosis), bleeding 
into the knee joint (hemarthrosis), reduced range of motion or abnormal walking (gait status 
abnormality) (temporary), localized pain, sensation decrease at incision site, inflammation of 
knee, infection, breakdown of articular cartilage (chondrolysis), fever, inflammation of the knee 
joint (synovitis), deep vein blood clot (deep vein thrombosis), treatment failure due to 
rehabilitation non-compliance, swelling of the knee, bruising of the knee, break in bone 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 77 of 101 
Document Date: 27OCT2016; Version 4.0 
(fracture), nerve injury, tendon injury, delayed wound healing, vascular injury, conversion to 
mini-open or open procedure vs. arthroscopic procedure, and/or additional surgery to fix 
problems associated with the first surgery. 
 
The potential medical risks associated with the study device are prolonged surgery time due to 
device breakage or malfunction, patient burn, and/or inadvertent tissue removal.  
 
Your study doctor is experienced in this type of surgery, but the results of this surgery cannot be 
guaranteed. It is possible that the surgery will not reduce the pain or disability felt before 
surgery. In addition, the pain or disability may be worse after the surgery. It is possible that by 
being in the study, you can have problems and/or side effects not know at this time. There is 
some element of this risk in all surgeries, whether or not you receive the study device.  
 
If you choose to take part in this study, you will be informed of any significant new findings 
(either good or bad), such as changes in the risks or benefits resulting from participation in the 
study, that might cause you to change your mind about continuing in the study. You may be 
asked to sign a new consent form if this occurs.  
 
Participating in more than one study may increase risks to you and may affect study results. You 
should tell your study doctor if you are considering joining another study. 
 
   Women as Study Subjects:  If you are a woman and are pregnant you cannot be in this 
study. If a woman is pregnant or nursing a child when she has medication associated with 
surgery there may be risks to the unborn baby or nursing child. 
 
If you think that you are pregnant during the study, you must tell the study doctor immediately. 
If you become pregnant before the surgery, you will be removed from the study.  
 
   Potential Benefits:  You may not benefit directly from participating in this study. If you 
choose to participate in the study, your condition may or may not improve. The potential benefits 
of the study device are minimal thermal penetration and precise and efficient tissue removal. The 
information collected in this study to determine the safety and effectiveness of Radiofrequency 
Debridement may benefit future patients undergoing arthroscopic knee surgery.  
 
   Treatment Options:  If you choose not to participate in this study, there are other treatments 
available to you. These include receiving the treatment that is routinely offered by this 
clinic/hospital for a chondral lesion and torn meniscus or not have any treatment at all. These 
alternatives may have similar and/or additional risks and precautions. Your doctor will have 
additional information on the alternative treatments.  
 
If you choose to participate in this study, you will be asked not to have another surgical treatment 
for your knee, unless you have recurring or new pain and/or symptoms, until the 104th week (2 
year) visit is complete.  
 
   Confidentiality and Privacy:   All persons associated with this study, including study 
doctors, coordinators, nurses and delegates (hereby referred to as “study personnel”) and the 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 78 of 101 
Document Date: 27OCT2016; Version 4.0 
sponsor (Smith & Nephew) or its designee are committed to respecting your privacy. No other 
persons will have access to your personal health information or other identifying personal 
information without your consent, unless required by law. If you choose to participate in this 
study, your personal doctor may be informed.   
 
The study information collected will be part of what is called your “personal health information” 
and is identifying information about you that relates to your health or the provision of health care 
services to you. Your personal health information will include the information from the 
procedures described in this consent form, as well as other information about you, such as your 
name and address. The study information collected on you will leave the country. 
 
Any personal health information collected or other information related to you will be coded by 
screening numbers to ensure that persons outside of the study will not be able to identify you. 
The study personnel are in control of the screening number code key, which is needed to connect 
your personal health information to you. Our guidelines include the following: 
 
 All information that identifies you, both paper copy and electronic information, will be 
kept confidential and stored and locked in a secure place that only the study personnel 
will be able to access.  
 Electronic files will be stored securely on hospital or institutional networks or securely 
on any portable electronic devices. 
 No information identifying you will be allowed off site in any form. Examples include 
your hospital or clinic charts, copies of any part of your charts, or notes made from your 
charts. 
 
It is important to understand that despite these protections being in place, there continues to be 
the risk of unintentional release of information. The study personnel will protect your records 
and keep all the information in your study file confidential to the greatest extent possible. The 
chance that this information will be accidentally released is small. 
 
By signing this form, you are authorizing access to your medical records by the study personnel, 
authorized representatives (i.e., study monitor) of the sponsoring company, the Research Ethics 
Board (REB), and by government regulatory authorities (i.e., Health Canada (HC), the US Food 
and Drug Administration (FDA), the Department of Health and Human Services, and/or 
regulatory agencies from other countries). Such access will be used for the purpose of verifying 
the authenticity and accuracy of the information collected for the study and for checking patient 
safety, without violating your confidentiality to the extent permitted by applicable laws and 
regulations.  
 
Federal and Provincial Data Protection regulations, including the Personal Information 
Protection and Electronic Documents Act (PIPEDA 2000) and the Personal Health Information 
Protection Act (PHIPA 2004) of Ontario, protect your personal information. They also give you 
the right to control the use of your personal information (including personal health information) 
and require your written permission for this personal information to be collected, used, or 
disclosed for the purposes of this study, as described in this consent form. You have the right to 
review and copy your personal information collected in this study. However, if you decide to be 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 79 of 101 
Document Date: 27OCT2016; Version 4.0 
in this study or choose to withdraw from it, your right to look at or copy your personal 
information related to this study will be delayed until after the research study is completed.  
 
Photographs may be taken of your knee before, during, and after the surgery; however, your 
identity will not be revealed. 
 
By HC regulations, the study sites and the sponsor will keep your study records for 25 years 
from the conclusion of the study. Your study records will then be destroyed in a secure manner 
once the retention period has elapsed.  
 
A description of this research study will be available on http://www.ClinicalTrials.gov, as 
required by US Law. This web site will not include information that can identify you. At most, 
the web site will include a summary of the results. You can search this web site at any time. 
 
   Study Results: The results of this study may be presented at conferences, seminars or other 
public forums, and published in journals, but at no time will you be identified. No information 
will be used in these presentations that would disclose your identity as a study subject. The 
analyzed data may also be used to plan for future research studies or to prepare reports or 
marketing applications to regulatory agencies. 
 
   Participation and Withdrawal:  Participation in any research study is voluntary. If you 
choose not to participate, you and your family will continue to have access to customary care at 
this study site. If you decide to participate in this study you can change your mind without giving 
a reason, and you may withdraw from the study at any time without any effect on the care you 
and your family will receive at this study site. If you decide to withdraw your consent to 
participate in this study, you must write a letter to the study doctor.  
 
The sponsor, the study doctor, HC, the FDA, or the REB may withdraw you from the study 
without your consent under the following circumstances:  
 
 
to protect your health and safety,  
 
failure to comply with study procedures,  
 
failure to later consent to any changes made in the study plan, or 
   the study is terminated for any reason. 
 
If you withdraw from the study, the data collected for you up to that time will be used to 
maintain the integrity of the study, but no more data on you will be collected. You will also be 
asked to return for a final visit for safety concerns and standard clinical care.  
 
 Compensation for Injury:  In no way does signing this form waive your legal rights nor 
release the study doctor(s), the study personnel, the sponsor (Smith & Nephew) or this study site 
from their legal and professional responsibilities.  
 
If you experience an injury or illness during the course of the study, you should seek medical 
treatment from a doctor, or treatment center of your choice, and promptly notify your study 
doctor.   

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 80 of 101 
Document Date: 27OCT2016; Version 4.0 
 
In the event that any illness or injury is determined to be related to the study procedure, your 
study doctor will provide essential medical treatment. You will not be charged for reasonable 
medical expenses required to treat the injury or illness if your study doctor has determined that 
the injury or illness is directly related to the study procedure and is not the result of a pre-existing 
condition caused by accidental re-injury or because you have not followed your study doctor's 
directions.    
 
If you have any questions about this, please ask the study doctor or study personnel. 
 
  Potential Costs/Reimbursements:  You will be compensated $60 (per visit) for Visits 1, 4, 
5, 6, and 7 and $100 (per visit) for Visits 3, 8, and 9 that you complete.  This will total $600 over 
the course of the study and is to compensate you for your time and any travel expenses 
associated with your participation in this research study. 
 
  Source of Funding for the Study:  Funding for this research study will be provided by the 
sponsor (Smith & Nephew).  
 
  Research Ethics Board Contact:  If you have any questions regarding your rights as a 
research subject in this study, you may contact name at xxx-xxx-xxxx. 
 
  Consent:  This consent form is only part of the process of informed consent. It should give 
you the basic idea of what the research study is about and what your participation will involve. It 
is not consent for surgery. You will be asked to sign a separate consent form for surgery. Your 
continued participation should be as informed as this initial consent so you should feel free to ask 
for clarification or new information throughout your participation in the study.  

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 81 of 101 
Document Date: 27OCT2016; Version 4.0 
A Prospective, Double Blinded, Multi-Center, Randomized, Controlled Trial to Evaluate 
Mechanical Debridement vs. Radiofrequency-Based Debridement in the treatment of Articular 
Cartilage Lesions 
 
I acknowledge that the research study described above has been explained to me and that any questions 
that I have asked have been answered to my satisfaction. I have been informed of the alternatives to 
participation in this study, including the right not to participate and the right to withdraw without 
compromising the quality of medical care at this study site for me and for other members of my family. 
As well, the potential risks, harms, and discomforts have been explained to me, and I also understand the 
benefits of participating in the research study. 
 
I understand that I have not waived my legal rights nor released the study doctors, or involved 
institutions, from their legal and professional duties. I know that I may ask now, or in the future, any 
questions that I have about the study or the research procedures. I have been assured that those records 
relating to me, and my care, will be kept confidential and that no information will be released or printed 
that would disclose personal identity without my permission unless required by law. I have been given 
sufficient time to read and understand the above information. 
 
I hereby freely and voluntarily consent to participate, and I will be given a signed copy of this consent 
form.  
 
_____________________________________ 
Name of Subject (please print) 
 
_____________________________________                  ________________________ 
Signature of Subject         
 
 
               Date  
 
 
 
 
 
 
_____________________________________  
 
Name/Status of Individual obtaining Consent (please print) 
 
 
 
_____________________________________                  ________________________ 
Signature of Individual obtaining Consent  
               Date 
 
 
 
 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 82 of 101 
Document Date: 27OCT2016; Version 4.0 
21.2 Appendix B – Draft Subject Questionnaires 
21.2.1 International Knee Documentation Committee (IKDC) 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
International Knee 
Documentation 
Committee (IKDC)  
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 83 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 84 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 85 of 101 
Document Date: 27OCT2016; Version 4.0 
21.2.2 Visual Analog Scale (VAS), knee pain 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
Visual Analogue Scale 
(VAS), knee pain 
X 
 
X 
X 
X 
X 
X 
X 
X 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 86 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
Visual Analog Scale 
 
 
How severe is your pain today?  Please place a vertical mark on the line below to indicate how 
bad you feel your pain is today. 
 
 
Visual Analogue Scale (VAS)* 
 
 
 
*A 10-cm baseline is recommended for VAS scales. 
From:  Acute Pain Management:  Operative or Medical Procedures and Trauma, Clinical Practice Guideline No. 1. 
AHCPR Publication No. 92-0032; February 1992. Agency for Healthcare Research & Quality, Rockville, MD; 
pages 116-117. 
 
No 
pain 
 
Pain as bad 
 as it could  
possibly be 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 87 of 101 
Document Date: 27OCT2016; Version 4.0 
 
21.2.3 Knee Injury and Osteoarthritis Outcome Score (KOOS) 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
Knee Injury and 
Osteoarthritis 
Outcome Score 
(KOOS) 
X 
 
 
X 
X 
X 
X 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 88 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 89 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 90 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 91 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 92 of 101 
Document Date: 27OCT2016; Version 4.0 
21.2.4 SF-12 
 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
SF-12 
X 
 
 
X 
X 
X 
X 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 93 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 94 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 95 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 96 of 101 
Document Date: 27OCT2016; Version 4.0 
21.2.5 EQ-5D-5L 
 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
EQ-5D-
5L 
X 
 
X 
X 
X 
X 
X 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 97 of 101 
Document Date: 27OCT2016; Version 4.0 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 98 of 101 
Document Date: 27OCT2016; Version 4.0 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 99 of 101 
Document Date: 27OCT2016; Version 4.0 
 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 100 of 101 
Document Date: 27OCT2016; Version 4.0 
21.2.6 Subject Satisfaction 
Procedure 
Screening/
Baseline 
Surgery   
Post-Treatment Follow-up Evaluation 
Visit 1 
Visit 2 
Visit 3 
Visit 4 Visit 5 Visit 6 
Visit 7 
Visit 8 
Visit 9 
Day  
-21 to 
 -1 
Day 0 
Day 10 
±3 
Days 
Wk 6 
± 5 
Days 
Wk 12 
± 7 
Days 
Wk 24 
± 14 
Days 
Wk 36 
±14 
Days 
Wk 52 
±28 
Days 
Wk 104 
±56 
Days 
Subject Satisfaction 
 
 
 
 
 
 
 
X 
X 

 
 
  
 
 
Protocol SM-2012-02                         Confidential & Proprietary                                        Page 101 of 101 
Document Date: 27OCT2016; Version 4.0 
 
 
Subject Satisfaction 
“All things considered (such as your pain level and functionality prior to treatment versus 
after treatment), how satisfied are you with the results of your treatment for your knee 
pain?” 
  Extremely satisfied 
  Very satisfied 
  Somewhat satisfied 
  Somewhat dissatisfied 
  Very dissatisfied  
                                                                    
  Extremely dissatisfied