Evaluation of the Calypso Knee System for Symptom Relief in Subjects With Medial Knee Osteoarthritis
Phase: NA
Conditions: Osteoarthritis, Knee
Sponsor: Moximed

CONFIDENTIAL and PROPRIETARY 
Clinical Study Protocol 
Study Title: Evaluation of the Calypso Knee System for Symptom Relief in Subjects with Medial Knee 
Osteoarthritis 
Short Title: Calypso Knee System Clinical Study 
Protocol No: CP0001 (Formerly CLIN102837) 
Revision: F  
Study Sponsor 
Moximed, Inc. 
46602 Landing Parkway 
Fremont, CA 94539 
Study Contact 
Rose Weinstein 
Director of Clinical Affairs 
Moximed Inc. 
Tel. (510) 887-3375  
Fax (510) 880-7179  
E-mail: rsweinstein@moximed.com
This document is a confidential communication of Moximed®, Inc. The recipient agrees that no 
unpublished information contained herein will be published or disclosed without prior written 
approval of Moximed, Inc. except that this document may be disclosed to appropriate institutional 
review boards, ethics committees or duly authorized representatives of the U.S. Food and Drug 
Administration or other responsible regulatory authorities under the condition that confidentiality is 
maintained. 
ClinicalTrials.gov Identifier: NCT03671213

 
 
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Investigator Protocol Signature Page  
 
Evaluation of the Calypso Knee System for Symptom Relief in Subjects with Medial Knee 
Osteoarthritis  
 
Short Title: Calypso Knee System Clinical Study 
Protocol No: CP0001 (Formerly CLIN102837) 
Revision: F 
 
I agree to conduct the investigation in accordance with the Calypso Knee System Clinical Study 
Protocol. 
 
 
 
 
____________________________________________________________________ 
                    Investigator Signature 
 
 
 
 
 
Date 
 
 
_____________________________________________________________________ 
                   Investigator Name (please print or type) 
 
 

 
 
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TABLE OF CONTENTS 
INVESTIGATOR PROTOCOL SIGNATURE PAGE ......................................................................... 2 
TABLE OF CONTENTS .............................................................................................................. 3 
PROTOCOL SUMMARY ............................................................................................................ 5 
ABBREVIATIONS ................................................................................................................... 12 
1.0 STUDY PURPOSE ........................................................................................................... 13 
1.1 
Introduction and Background .......................................................................... 13 
1.2 
Rationale for This Study................................................................................... 19 
1.3 
Device Name ................................................................................................... 21 
1.4 
Description of the Device ................................................................................ 21 
1.5 
Intended Use Statement ................................................................................. 23 
1.6 
Prior Clinical Investigation ............................................................................... 23 
2.0 PROTOCOL .................................................................................................................... 24 
2.1 
Study Objective ............................................................................................... 24 
2.2 
Study Scope and Participating Institutions ....................................................... 25 
2.3 
Patient Population........................................................................................... 25 
2.4 
Study Endpoints .............................................................................................. 28 
2.5 
Measures to Increase Validity and Minimize Bias ............................................ 29 
2.6 
Study Duration ................................................................................................ 30 
3.0 STUDY PROCEDURES ..................................................................................................... 30 
3.1 
Informed Consent ........................................................................................... 30 
3.2 
Enrollment Procedure ..................................................................................... 30 
3.3 
Patient Assessments........................................................................................ 31 
3.4 
Calypso Knee System Implant Removal ........................................................... 38 
3.5 
Termination of Subject Participation ............................................................... 39 
4.0 SAFETY REPORTING ...................................................................................................... 39 
4.1 
Adverse Events ................................................................................................ 40 
4.2 
Anticipated Adverse Events ............................................................................. 42 
4.3 
Subsequent Surgical Interventions of the Knee ............................................... 45 
4.4 
Device Malfunction ......................................................................................... 45 
5.0 STATISTICAL ANALYSIS PLAN ......................................................................................... 46 
5.1 
Additional Outcomes ....................................................................................... 46 
5.2 
Baseline Variables ........................................................................................... 46 
5.3 
Follow-Up and Reporting ................................................................................. 46 
6.0 STUDY MANAGEMENT .................................................................................................. 47 
6.1 
Sponsor Ethical and Regulatory Considerations ............................................... 47 
6.2 
Investigator Responsibilities ............................................................................ 49 
6.3 
Clinical Events Committee (CEC) ...................................................................... 52 
6.4 
Medical Monitoring ......................................................................................... 52 
6.5 
Protocol Deviations ......................................................................................... 52 
7.0 RISK ANALYSIS .............................................................................................................. 53 
7.1 
Potential Risks ................................................................................................. 53 

 
 
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7.2 
Minimizing Study Risks .................................................................................... 56 
7.3 
Benefit-Risk Summary ..................................................................................... 57 
7.4 
Anticipated Changes during the Investigation ................................................. 59 
8.0 MONITORING PLAN ...................................................................................................... 60 
9.0 REFERENCES ................................................................................................................. 61 
APPENDIX A:  DEFINITIONS ................................................................................................... 66 
 
List of Tables 
Table 1 Abbreviations .................................................................................................... 12 
Table 2 Calypso Knee System Implant Components ....................................................... 23 
Table 3 Imaging Assessment Schedule ........................................................................... 32 
Table 4 Calypso Knee System Clinical Study Schedule of Events ..................................... 37 
 
 

 
 
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Staged 
Enrollment: 
 
 
 
 
 
   
 
 
 
. 
Sample Size and 
Number of Sites: 
80 subjects will be enrolled in this study at up to 10 investigational sites located in the 
U.S. 
Patient 
Population: 
Male or female subjects age 25 to 65 years, with a diagnosis of medial knee 
osteoarthritis and study knee pain with an overall WOMAC pain score ≥ 40 (scale 0-
100). 
Inclusion/ 
Exclusion Criteria: 
Radiographic criteria (Inclusion #6 and Exclusion #3, 4, 5) will be assessed by an 
independent core laboratory per the Radiographic Evaluation Protocol (CLIN102792) 
as part of the screening process. 
Inclusion Criteria 
Subjects enrolled in the study must meet all of the following criteria: 
1. Subjects age 25 to 65 years at time of screening 
2. Body Mass Index (BMI) of < 35 
3. Weight < 300 lbs 
4. WOMAC pain ≥ 40  
5. Knee flexion ≥90⁰ and ≤ 140⁰ 
6. Clinical symptoms (such as pain primarily localized to the medial aspect of the 
study knee and generally exacerbated by weight bearing) and radiographic 
evidence, using a weight-bearing fixed flexion view, of osteoarthritis in the study 
knee as defined as KL grade of 1-4* 
7. Failed at least 6 months of non-operative treatment defined as at least one of the 
treatments per AAOS Treatment of Osteoarthritis of the Knee; Evidence based 
guideline 2nd Edition 2013  
Exclusion Criteria  
Subjects will be excluded from the study if any of the following conditions apply: 
Knee Osteoarthritis 
1. Radiographic evidence of large, defined as > Grade 2+, marginal osteophytes in 
the medial compartment of the study knee 
2. Bony erosion 
3. Clinical symptoms or radiographic evidence of osteoarthritis in the: 
a. Lateral compartment of the study knee defined as KL grade of > 2* 
b. Patellofemoral compartment of the study knee defined as KL grade > 3* 
4. Clinical symptoms or radiographic evidence of osteoarthritis at the contralateral 
knee that would preclude activity of daily living, stair climbing, stair descending, 

 
 
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or requires the use of an assist device* 
5. Mechanical axis alignment (Hip-Knee-Ankle) < -16⁰ (varus) or > 0⁰ (valgus) OR 
anatomic axis alignment < -10⁰ (varus) or > 6⁰ (valgus) as measured on a Long 
Standing AP X-ray view* 
6. Hyperextension >5⁰ 
7. Flexion contracture > 10⁰ 
8. Insufficiency of the cruciate and collateral ligaments, which would preclude 
stability of the Calypso Knee System 
9. Pathologic ligamentous (Lachman > 1)  or meniscal instability 
10. Previous knee surgeries: 
a. Lateral meniscectomy, patellar surgery, osteotomy, prior knee implant, or 
knee joint replacement of the study knee 
b. Joint modifying surgery in the study knee within 12 months of index 
procedure (e.g., ligament reconstruction, meniscus repair, cartilage 
transplantation, microfracture, etc.) 
c. 
Arthroscopic surgeries in the study knee within 3 months of index 
procedure for joint lavage, meniscectomy, chondral debridement, and 
loose body removal  
Joint or Bone Complications/Comorbidities 
11. Active infection, sepsis, osteomyelitis or history of septic arthritis in any joint 
12. Rheumatoid arthritis, other forms of inflammatory joint disease or autoimmune 
disorder 
13. Paget’s disease or metabolic disorders which may impair bone formation 
14. Osteomalacia or osteonecrosis (known or suspected) 
15. Known or suspected rapidly destructive OA (RDO) as determined by the 
investigator++ 
16. Charcot’s joint disease  
17. Osteoporosis Self-Assessment Tool (OST) score of < 4 for women or < 6 for men 
AND a T-score less than -1.0 based on a DEXA scan of the proximal femur 
(preferred) or lumbar spine. All subjects with an OST score < 4 for women or < 6 
for men will undergo a DEXA scan to determine the bone mineral density T-score. 
18. Steroid treatment (oral or IV), medication use that affects bone metabolism (such 
as chemotherapy) or radiotherapy within 6 months of index procedure 
19. Bone malignancy (active or history) 
Other Complications/Comorbidities 
20. Allergy or hypersensitivity to cobalt, chromium, iron, or nickel metals (suspected 
or documented) 
21. Life expectancy estimated to be less than 5 years (i.e., malignancies, end stage 
liver, kidney, cardiac failure) 
22. Co-morbidities that could impact study participation or results: 
a. Neurological disorders affecting gait  
b. Neuropathic pain or fibromyalgia, restless leg syndrome, complex regional 
pain syndrome or Reflex Sympathetic Dystrophy (RSD) or pain requiring 

 
 
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chronic pain management 
c. 
Severe neurosensory deficits, muscular atrophy, neuromuscular disease 
d. Immunologically suppressed or immunocompromised patients such as HIV 
e. Diabetes mellitus requiring daily insulin therapy  
f. 
Radicular symptoms associated with lumbar spine pathology 
g. Significant psychiatric disorders (e.g., major depression, anxiety disorders, 
bipolar disorder, and schizophrenia) 
h. Substance and alcohol dependence and abuse (meeting standard 
diagnostic criteria described in the Diagnostic and Statistical Manual of 
Mental Disorders DSM-V) 
General Conditions 
23. Pregnancy or planning to become pregnant 
24. Subjects unable to give voluntary written informed consent to participate 
25. Subjects who are currently involved in any investigational drug or device trial or 
have been enrolled in such trials within 3 months of index procedure  
26. Other factors that the investigator feels would interfere with the participation 
and completion of the study such as:  
a. Unable to understand the clinical investigation or cooperate with 
investigational procedures 
b. Planned relocation or unable to return for required follow-up visits 
c. 
Active litigation for  musculoskeletal injuries or disorders 
d. Active workers compensation or Labor & Industries claim for 
musculoskeletal injury or disorder  
*Radiographic analysis will be provided by an independent imaging core laboratory to 
support the investigator in confirming inclusion/exclusion criteria prior to enrollment. 
+Altman RD, Gold GE Atlas of individual radiographic features in osteoarthritis, revised. 
Osteoarthritis Cartilage. 2007;15 Suppl A:A1-56 (pg. 42-49). 
++Hart G, Fehring T, Rapidly destructive osteoarthritis can mimic infection. Arthroplasty 
Today. 2016; 2(1):15-18. 
Primary Endpoint:  
24 month composite endpoint demonstrating non-inferiority of the Calypso Knee 
System to HTO data. A subject is a responder if all of the following components are 
met at 24 months: 
• 
Clinically significant improvement of at least 20% from baseline on the WOMAC 
pain questions in the KOOS Knee questionnaire with a change of ≥10 points  
• 
Clinically significant improvement of at least 20% from baseline on the WOMAC 
function questions in the KOOS Knee questionnaire with a change of ≥10 points  
• 
Freedom from the following device-related serious adverse events:  
o 
deep infection requiring surgical intervention (Both arms)  
o 
damage to adjacent neurovascular or ligament structures necessitating 
reconstruction (Both arms)  
o 
non-union (HTO only)  
• 
Maintenance of implant integrity as evaluated by radiographic assessment 
NOTE: A subject will be considered a non-responder if they have a conversion to 

 
 
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arthroplasty or loss of implant integrity of the Calypso Knee System at 24 months. 
Secondary 
Endpoints: 
Secondary endpoints demonstrating superiority of the Calypso Knee System to HTO 
data for each of the following: 
Recovery: 
1. 
Time to full weight bearing 
Early WOMAC Pain and Function: 
2. 
Percent change from baseline to 3 months on the WOMAC pain in the Knee 
injury and Osteoarthritis Outcome Score (KOOS Knee Survey) 
3. 
Percent change from baseline to 3 months on the WOMAC function in the Knee 
injury and Osteoarthritis Outcome Score (KOOS Knee Survey) 
Durability of WOMAC Pain and Function: 
4. 
Percent change from baseline to 24 months on the WOMAC pain in the Knee 
injury and Osteoarthritis Outcome Score (KOOS Knee Survey) 
5. 
Percent change from baseline to 24 months on the WOMAC function in the Knee 
injury and Osteoarthritis Outcome Score (KOOS Knee Survey)  
Additional 
Observations: 
Safety Observations: 
• 
Knee Range of Motion (ROM) 
o 
Measured passively defined as degrees of flexion and extension  
• 
Adverse Events by type, over time, severity, seriousness, and relatedness 
• 
Secondary surgical interventions by type of surgical intervention (revision, 
removal, re-operation (includes conversion to arthroplasty) supplemental 
fixation, other intervention) 
• 
Metal ion levels  
• 
In the event of a Calypso Knee System removal, the following assessments will be 
evaluated: 
o 
Radiographic evaluations  
o 
MRI assessment as available 
o 
Calypso Knee System (implant) retrieval analysis 
o 
Histology 
o 
Metal Ion levels 
o 
Arthroplasty conversion data, if applicable 
Effectiveness/Other Observations: 
• 
Patient reported knee outcome measures and activity (KOOS Knee Survey, KSS, 
Subject Activity and Satisfaction, SF-12 Health Survey)  
• 
Investigator reported KSS 
Statistical 
Analyses: 
Primary Statistical Analysis 
The primary objective is to establish that the Calypso Knee System is non-inferior to 
HTO on a responder analysis combining pain, function, specified device-related SAEs, 
and implant integrity. A subject is considered a responder if he/she meets all success 
criteria that comprise the definition of the composite end-point at 24 months.  
Secondary Statistical Analysis 
Secondary Statistical Analysis will only be conducted upon a successful primary 
analysis of non-inferiority. Analysis of secondary objectives will take a hierarchical 

 
 
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approach. These analyses will be conducted sequentially, starting from the first 
objective with progression towards the fifth objective. Each subsequent objective is 
only analyzed when all of the previous analyses are successful at demonstrating 
superiority.   
Additional Observations Analysis 
Traditional confidence intervals and p-values will be reported for these analyses, as 
applicable. 
• 
Knee Range of Motion (ROM) – evaluation using Calypso Knee System at baseline 
compared to 24 months 
• 
Adverse Events by type over time, severity, seriousness, and relatedness. AEs will 
be tabulated and summarized as counts and percentages.  AEs will also be cross-
tabulated according to: 
o 
Severity; 
o 
Unanticipated Adverse Device Effect (UADE) 
o 
Seriousness (Serious Adverse Event (SAE), Non-serious AE); 
o 
Device-Relatedness (Unrelated, Possibly Related, Probably Related, 
Definitely Related); 
o 
Procedure-Relatedness (Unrelated, Possibly Related, Probably Related, 
Definitely Related). 
• 
Secondary surgical interventions by type of surgical intervention (revision, 
removal, re-operation (includes conversion to arthroplasty) supplemental 
fixation, other intervention)  
• 
Changes in patient reported knee outcome measures and activity (KOOS Knee 
Survey, KSS, Subject Activity and Satisfaction, SF-12 Health Survey) as compared 
to baseline 
• 
Changes in Investigator reported KSS 
Study Duration: 
All subjects included in this study will return for follow-up visits at 6 weeks and 3, 6, 
12, 18, and 24 months, then annually through 5 years.  
References: 
CLIN102840: Calypso Knee System Metal Ion Protocol 
LBL102812: Calypso Knee System, Instructions for Use - Product Insert 
LBL102811: Calypso Knee System Instruments, Instructions for Use - Product Insert 
CLIN102845: Calypso Knee System Surgical Technique Guide 
CLIN102792: Calypso Clinical Study Radiographic Evaluation Protocol  
CLIN102799: Calypso Clinical Study Informed Consent 
CLIN102852: Calypso Clinical Study Implant Retrieval Protocol 
CLIN102838: Calypso Knee System Rehabilitation Guideline 
CLIN102842: Calypso Clinical Study Investigator’s Agreement 
CLIN103113: Statistical Considerations and Preliminary Propensity Score (PS) Design 
Memorandum  
CLIN102839: Calypso Clinical Study Surgeon Training 
CLIN102853: Calypso Clinical Study Monitoring Plan 
CLIN102859: Calypso Clinical Study CEC Charter 
 

 
 
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PRINCIPAL CONTACTS 
 
 
Name, Address and Contact  
Principal Investigator 
 
Study Sponsor Contact 
Rose S. Weinstein 
Director, Clinical Affairs 
Moximed Inc. 
Tel. (510) 887-3375 
Fax. (510) 880-7179 
E-mail: rsweinstein@moximed.com 
Study Statistician 
  
  
 
 
Medical Monitor 
  
  
 
Data Management 
 
 
 
Clinical Events Committee (CEC) 
 
 
Imaging Core Lab 
 
 
Metal Ion Core Lab 
 
 
Implant Retrieval Analysis Core Lab 
 
 
  
Histology  
 
 
 
 
 
 
 
 
 
 
 

 
 
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ABBREVIATIONS  
Table 1 Abbreviations  
AE 
Adverse Event 
AT 
As Treated Patient Population 
BMI 
Body Mass Index 
CA 
Competent Authority 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CFR-PEEK 
Carbon-fiber reinforced polyetheretherketone 
CoCr 
Cobalt Chrome  
CRF 
Case Report Form 
CWO 
Closed Wedged Osteotomy 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HA 
Hyaluronic acid, sodium hyaluronate, hyaluronan 
IA 
Intra-articular 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
HTO 
High Tibial Osteotomy 
ITT 
Intent to Treat 
ISO 
International Organization for Standardization 
IRB 
Institutional Review Board 
KOOS Knee Survey 
Knee injury and Osteoarthritis Outcome Score Knee Survey 
KL (or K&L) 
Kellgren and Lawrence 
KSS 
Knee Society Score 
LOCF 
Last Observation Carried Forward 
MDD  
Medical Device Directive 
NSAIDs 
Nonsteroidal anti-inflammatory drugs 
OA 
Osteoarthritis 
OMERACT-OARSI 
Outcome Measures in Rheumatology-Osteoarthritis Research Society 
International  
OUS 
Outside of the United States 
OWO 
Open Wedge Osteotomy  
PHI 
Personal Health Information 
PD 
Protocol Deviation 
PI 
Principal Investigator 
PP 
Per Protocol Patient Population 
PA 
Posterior-Anterior 
PCU 
Polycarbonate-urethane 
QA 
Quality Assurance 
QOL 
Quality of Life 

 
 
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RDO 
Rapidly Destructive OA  
SAE 
Serious Adverse Event 
SD 
Standard Deviation  
SF-12 Health Survey 
Short Form Health Survey-12 
TKA 
Total Knee Arthroplasty 
TKR 
Total Knee Replacement 
UADE 
Unanticipated Adverse Device Effect 
UKA 
Unicompartmental Knee Arthroplasty 
USA 
United States of America 
WOMAC 
Western Ontario and McMaster Universities Arthritis Index  
 
1.0 
STUDY PURPOSE 
 
1.1 
Introduction and Background 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
   

 
 
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1.1.2 
Education 
 
 
 
 
1.1.3 
Weight loss 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.1.4 
Exercise 
 
 
 
 
 
 
 
1.1.5 
Physical Therapy 
 
 
 
 
 
 
 
  
 
 

 
 
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1.1.6 
Knee Braces and Orthotics 
 
 
 
 
 
 
 
 
 
 
 
1.1.7 
Pharmacologic Approaches 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
1.1.8 
Current Surgical Treatment Options  
 
 
 
 
  
 
 
 
 

 
 
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High Tibial Osteotomy  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Joint Unloading with External Joint Distraction 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Knee Arthroplasty 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 

 
 
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1.1.9 
Conclusions 
 
 
 
 
 
  
 
 
 
  
 
1.2 
Rationale for This Study  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

 
 
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1.4.1 
Mechanism of Action 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
   
 
 
 

 
 
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2.0 
PROTOCOL  
 
2.1 
Study Objective 
 
The Calypso Clinical study is a pivotal study to evaluate the safety and effectiveness of the Calypso Knee 
System when used in subjects with symptomatic osteoarthritis of the medial compartment of the knee. 
2.1.1 
Study Design Overview 
 
The Calypso Clinical Study is a prospective, multicenter clinical study comparing the Calypso Knee System to 
the cohort of subjects treated with High Tibial Osteotomy (HTO) from a recent non-randomized trial (GOAL 
study).  A total of 80 subjects will be enrolled in this study at up to 10 investigational sites located in the U.S. 
using a staged enrollment. 
 
 
 
 
   
 
 
 
 
 
The subject population for this study is male or female subjects age 25 to 65 years, with a diagnosis of medial 
knee osteoarthritis and study knee pain with an overall WOMAC pain score ≥ 40 (scale 0-100). 
 
All subjects included in this study will return for follow-up visits at 6 weeks and 3, 6, 12, 18, and 24 months, 
then annually through 5 years.  
 
At each follow-up visit, safety and effectiveness data will be collected. Subjects will be interviewed to 
determine if adverse events (AEs) were experienced since the previous follow-up visit. A complete 
orthopaedic knee assessment will be performed at baseline for all subjects and again during each follow-up 
visit. All subjects will be required to complete the KOOS Knee Survey and KSS to evaluate function, pain, and 
quality of life at each follow-up visit.  

 
 
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Radiographic evaluations will be performed at pre-op, prior to discharge, 6 weeks, 3 months, 6 months, 12 
months, 18 months,  24 months and annually thereafter through 5 years for all subjects.  Radiographic 
evaluations will also be performed within 60 days prior to any planned Calypso Knee System removal.  
 
MRI evaluations will be performed at the pre-procedure and at 2 and 5 year follow-up visits.  
 
2.2 
Study Scope and Participating Institutions 
 
 
 
 
2.3 
Patient Population 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
2.3.1 
Inclusion/Exclusion Criteria 
Radiographic criteria (Inclusion #6 and Exclusion #3, 4, 5) will be assessed by an independent core 
laboratory per the Radiographic Evaluation Protocol (CLIN102792) as part of the screening process. 
 
Inclusion Criteria 
Subjects enrolled in the study must meet all of the following criteria: 
1. Subjects age 25 to 65 years at time of screening 
2. Body Mass Index (BMI) of < 35 
3. Weight < 300 lbs 

 
 
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4. WOMAC pain ≥ 40  
5. Knee flexion ≥90⁰ and ≤ 140⁰ 
6. Clinical symptoms (such as pain primarily localized to the medial aspect of the study knee and 
generally exacerbated by weight bearing) and radiographic evidence, using a weight-bearing fixed 
flexion view,  of osteoarthritis in the study knee as defined as KL grade of 1-4* 
7. Failed at least 6 months of non-operative treatment defined as at least one of the treatments per 
AAOS Treatment of Osteoarthritis of the Knee; Evidence based guideline 2nd Edition 2013  
 
Exclusion Criteria  
Subjects will be excluded from the study if any of the following conditions apply: 
Knee Osteoarthritis 
1. Radiographic evidence of large, defined as > Grade 2+, marginal osteophytes in the medial 
compartment  of the study knee 
2. Bony erosion 
3. Clinical symptoms or radiographic evidence of osteoarthritis in the: 
a. Lateral compartment of the study knee defined as KL grade of >2* 
b. Patellofemoral compartment of the study knee defined as KL grade > 3* 
4. Clinical symptoms or radiographic evidence of osteoarthritis at the contralateral knee that would 
preclude activity of daily living, stair climbing, stair descending, or requires the use of an assist 
device* 
5. Mechanical axis alignment (Hip-Knee-Ankle) < -16⁰ (varus) or > 0⁰ (valgus) OR anatomic axis 
alignment < -10⁰ (varus) or > 6⁰ (valgus) as measured on a Long Standing AP X-ray view* 
6. Hyperextension > 5⁰ 
7. Flexion contracture > 10⁰ 
8. Insufficiency of the cruciate and collateral ligaments, which would preclude stability of the Calypso 
Knee System 
9. Pathologic ligamentous (Lachman > 1)  or meniscal instability 
10. Previous knee surgeries: 
a. Lateral meniscectomy, patellar surgery, osteotomy, prior knee implant, or knee joint 
replacement of the study knee 
b. Joint modifying surgery in the study knee within 12 months of index procedure (e.g., 
ligament reconstruction, meniscus repair, cartilage transplantation, microfracture, etc.) 
c. 
Arthroscopic surgeries in the study knee within 3 months of index procedure for joint lavage, 
meniscectomy, chondral debridement, and loose body removal  
Joint or Bone Complications/Comorbidities 
11. Active infection, sepsis, osteomyelitis or history of septic arthritis in any joint 
12. Rheumatoid arthritis, other forms of inflammatory joint disease or autoimmune disorder 
13. Paget’s disease or metabolic disorders which may impair bone formation 
14. Osteomalacia or osteonecrosis (known or suspected) 
15. Known or suspected rapidly destructive OA (RDO) as determined by the investigator+ 
16. Charcot’s joint disease  
17. Osteoporosis Self-Assessment Tool (OST) score of < 4 for women or < 6 for men AND a T-score less 
than -1.0 based on a DEXA scan of the proximal femur (preferred) or lumbar spine. All subjects with 

 
 
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an OST score < 4 for women or < 6 for men will undergo a DEXA scan to determine the bone mineral 
density T-score. 
18. Steroid treatment (oral or IV), medication use that affects bone metabolism (such as chemotherapy) 
or radiotherapy within 6 months of index procedure 
19. Bone malignancy (active or history) 
Other Complications/Comorbidities 
20. Allergy or hypersensitivity to cobalt, chromium, iron, or nickel metals (suspected or documented) 
21. Life expectancy estimated to be less than 5 years (i.e., malignancies, end stage liver, kidney, cardiac 
failure) 
22. Co-morbidities that could impact study participation or results: 
a. Neurological disorders affecting gait  
b. Neuropathic pain or fibromyalgia, restless leg syndrome, complex regional pain syndrome or 
Reflex Sympathetic Dystrophy (RSD) or pain requiring chronic pain management 
c. 
Severe neurosensory deficits, muscular atrophy, neuromuscular disease 
d. Immunologically suppressed or immunocompromised patients such as HIV 
e. Diabetes mellitus requiring daily insulin therapy  
f. 
Radicular symptoms associated with lumbar spine pathology 
g. Significant psychiatric disorders (e.g., major depression, anxiety disorders, bipolar disorder, 
and schizophrenia) 
h. Substance and alcohol dependence and abuse (meeting standard diagnostic criteria 
described in the Diagnostic and Statistical Manual of Mental Disorders DSM-V) 
General Conditions 
23. Pregnancy or planning to become pregnant 
24. Subjects unable to give voluntary written informed consent to participate 
25. Subjects who are currently involved in any investigational drug or device trial or have been enrolled in 
such trials within 3 months of index procedure  
26. Other factors that the investigator feels would interfere with the participation and completion of the 
study such as:  
a. Unable to understand the clinical investigation or cooperate with investigational procedures 
b. Planned relocation or unable to return for required follow-up visits 
c. 
Active litigation for  musculoskeletal injuries or disorders 
d. Active workers compensation or Labor & Industries claim for musculoskeletal injury or 
disorder 
*Radiographic analysis will be provided by an independent imaging core laboratory to support the investigator 
in confirming inclusion/exclusion criteria prior to enrollment. 
 
+Altman RD, Gold GE Atlas of individual radiographic features in osteoarthritis, revised. Osteoarthritis 
Cartilage. 2007;15 Suppl A:A1-56 (pg. 42-49). 
++Hart G, Fehring T, Rapidly destructive osteoarthritis can mimic infection. Arthroplasty Today. 2016; 2(1):15-
18. 
 

 
 
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2.4 
Study Endpoints 
 
2.4.1 
Primary Endpoint 
The primary endpoint is a 24 month composite endpoint demonstrating non-inferiority of the Calypso Knee 
System to HTO data. A subject is a responder if all of the following components are met at 24 months: 
 
• 
Clinically significant improvement of at least 20% from baseline on the WOMAC pain questions in the 
KOOS Knee questionnaire with a change of ≥10 points  
• 
Clinically significant improvement of at least 20% from baseline on the WOMAC function questions in 
the KOOS Knee questionnaire with a change of ≥10 points  
• 
Freedom from the following device-related serious adverse events:  
o 
deep infection requiring surgical intervention (Both arms)  
o 
damage to adjacent neurovascular or ligament structures necessitating reconstruction (Both 
arms)  
o 
non-union (HTO only)  
• 
Maintenance of implant integrity as evaluated by radiographic assessment 
 
NOTE: A subject will be considered a non-responder if they have a conversion to arthroplasty or loss of 
implant integrity of the Calypso Knee System at 24 months   
 
Details of the radiographic assessment for implant integrity may be found in the Radiographic Evaluation 
Protocol (CLIN102792). 
2.4.2 
Secondary Endpoints  
Secondary endpoints demonstrating superiority of the Calypso Knee System to HTO data for each of the 
following: 
 
Recovery: 
1. 
Time to full weight bearing 
Early WOMAC Pain and Function: 
2. 
Percent change from baseline to 3 months on the WOMAC pain in the Knee injury and Osteoarthritis 
Outcome Score (KOOS Knee Survey) 
3. 
Percent change from baseline to 3 months on the WOMAC function in the Knee injury and 
Osteoarthritis Outcome Score (KOOS Knee Survey) 
Durability of WOMAC Pain and Function: 
4. 
Percent change from baseline to 24 months on the WOMAC pain in the Knee injury and Osteoarthritis 
Outcome Score (KOOS Knee Survey) 
5. 
Percent change from baseline to 24 months on the WOMAC function in the Knee injury and 
Osteoarthritis Outcome Score (KOOS Knee Survey) 
 
2.4.3 
Additional Observations 
 
Safety Observations: 
• 
Knee Range of Motion (ROM)  
o 
Measured passively defined as degrees of flexion and extension  
• 
Adverse Events by type, over time, severity, seriousness, and relatedness 

 
 
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• 
Secondary surgical interventions by type of surgical intervention (revision, removal, re-operation 
(includes conversion to arthroplasty) supplemental fixation, other intervention) 
• 
Metal ion levels  
• 
In the event of a Calypso Knee System removal, the following assessments will be evaluated: 
o 
Radiographic evaluations  
o 
MRI assessment as available 
o 
Calypso Knee System (implant) retrieval analysis 
o 
Histology 
o 
Metal Ion levels 
o 
Arthroplasty conversion data, if applicable 
 
Effectiveness/Other Observations: 
• 
Patient reported knee outcome measures and activity (KOOS Knee Survey, KSS, Subject Activity and 
Satisfaction, SF-12 Health Survey)  
• 
Investigator reported KSS 
 
2.5 
Measures to Increase Validity and Minimize Bias  
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 

 
 
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2.6 
Study Duration 
All subjects included in this study will return for follow up visits at 6 weeks, 3 months, 6 months, 12 months, 
18 months and 24 months post index procedure. Evaluation of the primary endpoint will be completed on all 
subjects at 24 months post procedure. Follow-up visits will continue annually for a total of 5 years.  
 
3.0 
STUDY PROCEDURES 
3.1 
Informed Consent  
 
 
 
  
 
 
 
 
 
 
   
3.2 
Enrollment Procedure  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
  
 

 
 
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3.3 
Patient Assessments 
3.3.1 
Patient Screening (Pre-Op Visit) 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
  
 
 
 
 
 
 
   
  
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
   
 
 
 

 
 
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Treatment Procedures 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
 
 
 
 
 

 
 
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• 
 
3.3.3 
Concomitant Procedures 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
3.3.4 
Post Procedure Care (Discharge) 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
3.3.5 
Post procedure and post-operative rehabilitation recommendations  
 
 
 
 
   
 
 
 

 
 
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3.3.6 
Post Procedure Follow Up Assessments 
 
All subjects included in this study will return for follow up visits at 6 weeks, 3 months, 6 months, 12 months, 
18 months and 24 months post index procedure and annually for 5 years post procedure. 
3.3.6.1 6 week follow-up (±14 days) 
• 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
3.3.6.2 3 and 6 month Follow-Up (±31 days) 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 

 
 
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 
 
  
 
 
 
  
3.3.6.3 1 year, 18 months, 2, 3, 4, and 5 Year Follow-up (± 60 days) 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 

 
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3.5 
Termination of Subject Participation 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
• 
Subject Lost to Follow-Up:  Unable to locate subject despite at least three documented attempts to 
notify the subject via telephone or e-mail, and by certified mail. A subject will not be considered lost 
to follow-up until the last scheduled follow-up visit (60 month (5 years) study time point). 
• 
Subject Withdraw Consent:  The subject requests to terminate his/her involvement in the study, 
therefore withdrawing his/her consent to participate in the study (the investigator must thoroughly 
document the reasons for termination). Attempts will be made to retrieve any follow-up data, prior 
to the time point at which voluntary consent was withdrawn, when available, in particular regarding 
possible AEs at the time of study discontinuation. 
• 
Subject Withdrawn by Investigator: Subjects who are withdrawn by the Investigator for any reason 
prior to study completion. 
• 
Subject Death:  If possible, an autopsy and/or death certificate should be obtained in order to 
document the cause of death. 
 
All serious device-related adverse events will be followed until resolution, stabilization or 30 days after the last 
subject enrolled has completed the study, whichever occurs first. 
 
4.0 
SAFETY REPORTING 
 
 
 
 
 
   
 
 

 
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5.0 
STATISTICAL ANALYSIS PLAN 
 
Refer to the Statistical Considerations and Preliminary Propensity Score (PS) Design Memorandum 
(CLIN103113) for the Calypso Clinical Study for primary and secondary endpoint study analysis, analysis 
population, sample size and power, evaluation of missing data, and baseline covariates against endpoint 
success rates. 
 
5.1 
Additional Outcomes   
 
Safety Observations: 
• 
Knee Range of Motion (ROM)  
o 
Measured passively defined as degrees of flexion and extension  
• 
Adverse Events by type, over time, severity, seriousness, and relatedness 
• 
Subsequent surgical interventions of the knee by type of surgical intervention (revision, removal, re-
operation (includes conversion to arthroplasty) supplemental fixation, other intervention) 
• 
Metal ion levels  
• 
In the event of a Calypso Knee System removal, the following assessments will be evaluated: 
o 
Radiographic evaluations  
o 
MRI assessment as available 
o 
Calypso Knee System (implant) retrieval analysis 
o 
Histology 
o 
Metal Ion levels 
o 
Arthroplasty conversion data, if applicable 
Effectiveness/Other Observations: 
• 
Patient reported knee outcome measures and activity (KOOS Knee Survey, Activity Questionnaire, SF-
12 Health Survey, Patient Satisfaction)  
• 
Investigator reported KSS 
 
5.2 
Baseline Variables  
 
Demographic and baseline variables will be summarized. Sample sizes, means, standard deviations and ranges 
will be presented for all continuous variables. 
 
5.3 
Follow-Up and Reporting 
 
All subjects enrolled and devices used in the clinical study will be accounted for in the final report. All reasons 
for exclusion from analysis will be carefully documented. Similarly, for all subjects and devices included in an 
analysis population, the measurements of all important variables must be accounted for at all relevant time 
points. Additional information that is available on subjects screened for entry but not enrolled will also be 
summarized.  
 

 
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Subjects with early termination will be identified and a descriptive analysis of them provided, including the 
reasons for their loss to follow-up and known treatment outcome.  
 
Subjects requiring removal of the Calypso Knee System will continue to participate in follow-up through the 
duration of the study. These subjects will take part in all protocol required follow up examinations, test, and 
the completion of questionnaires.  
 
6.0 
STUDY MANAGEMENT  
 
6.1 
Sponsor Ethical and Regulatory Considerations 
 
 
 
 
 
 
 
 
General Duties 
 
 
 
 
   
 
 
 
   
 
Selection of Clinical Sites 
 
 
 
 
 
 
 
 
 
 
Site Training 
 
 
 

 
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Investigator Training 
 
 
 
 
 
 
 
 
 
Subject Confidentiality 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Data Management 
 
 
 
   
 
Record Retention 
 
 
 
 
 

 
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6.2 
Investigator Responsibilities 
 
 
 
 
 
 
 
 
 
 
 
6.2.1 
IRB Approval and Informed Consent 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
   
 
 
 

 
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6.2.2 
Data Collection and Reporting 
 
 
 
 
 
 
 
 
 
6.2.3 
Data Completion and Submission 
 
 
 
 
  
 
6.2.4 
Device Accountability 
 
 
 
  
 
6.2.5 
Source Documents 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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6.3 
Clinical Events Committee (CEC) 
 
An independent Clinical Events Committee (CEC) will be established to adjudicate all serious adverse events 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
6.4 
Medical Monitoring 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.5 
Protocol Deviations 
 
 
 
  
 
 
 
 

 
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7.0 
RISK ANALYSIS  
 
7.1 
Potential Risks 
 
 
 
 
  
 
Surgical Risks 
 
 
   
 
1. Risks associated with general surgery include:  
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Risks associated with knee surgery include:  
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
• 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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• 
 
 
 
 
 
 
 
 
 
    
 
 
  
 
3. Risks associated with Calypso Knee System:   
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Risks Associated with Radiographs 
 
 
 

 
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• 
 
 
 
   
 
 
  
 
 
 
 
 
 
 
 
 
7.3 
Benefit-Risk Summary 
 
 
 
 
   
 
 
  
 
 
 
 
 
 
 
 
  
 
   
 
 
  
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 

 
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7.4 
Anticipated Changes during the Investigation 
 
There are no known anticipated changes of the Calypso Knee System during the investigation.  
 
 
 
 

 
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8.0 
MONITORING PLAN 
 
 
 
 
 
 
 
 
 
 
  
 
Site Qualification/Initiation Visits 
  
 
 
 
 
 
 
  
 
Interim Monitoring Visits 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 

 
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Site Close Out Visit 
 
 
 
 
  
 
Qualifications of Study Monitor 
 
 
  
 
9.0 
REFERENCES  
 
1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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17. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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APPENDIX A:  DEFINITIONS   
 
ANALGESIC 
A pain-relieving effect with no loss of consciousness 
 
BLEEDING COMPLICATION 
A procedure related hemorrhagic event that requires a transfusion or surgical repair.  
 
BURSITIS 
Bursitis is an inflammation of the native bursae that can result in irritation and pain. 
 
CELLULITIS 
A superficial, spreading infection of the skin and subcutaneous tissue, usually following lacerations 
and surgical wounds. The most common causative organism is penicillin sensitive streptococci. 
Cellulitis is characterized by signs of inflammation (local pain, tenderness, swelling and erythema). 
The border between involved and uninvolved skin is usually indistinct and systemic illness 
characterized by fever, chills, malaise and toxicity is frequently present. 
http://www.who.int/surgery/publications/en/SCDH.pdf 
 
DEEP VEIN THROMBOSIS 
Deep vein thrombosis (DVT) is a blood clot that forms in a vein deep in the body. 
Http://www.nhlbi.nih.gov/health/dci/diseases/dvt/dvt whatis.html 
 
DEVICE MALFUNCTION 
The failure of a device to meet its performance specifications or otherwise perform as intended. 
Performance specifications include all claims made in the labeling for the device. (21 CFR Part 803) 
 
DIABETES MELLITUS 
A condition caused by insufficient production of insulin resulting in abnormal metabolism of 
carbohydrates, fats and protein. Diabetes mellitus is defined as symptoms of hyperglycemia (thirst, 
polyuria, weight loss, visual blurring) and a casual plasma glucose concentration of ≥200 mg/dl; or a 
fasting plasma blood glucose concentration of ≥126 mg/dl; or a 2-hour post load glucose ≥200 mg/dl 
during an oral glucose tolerance test as described by the World Health Organization (WHO).  

 
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ENROLLED 
Subjects who sign informed consent and undergo an anesthesia start time for purposes of receiving 
the Calypso Knee System. 
 
HEMATOMA 
A localized mass of extravasated blood that is relatively or completely confined within an organ or 
tissue, a space, or a potential space that measures four centimeters or greater in diameter at the 
vascular access site, or those requiring transfusion or necessitating prolonged hospitalization. 
 
HEMORRHAGE 
An escape of blood through ruptured, or unruptured vessel walls. 
 
KNEE SCARRING, ARTHROFIBROSIS, OR PERIPROSTHETIC LOCAL ADHESIONS 
A process of fibrosis or proliferation of fibrotic tissue as part of the healing process.  May occur 
about the knee joint, intra-articular or extra-articular or present as periprosthetic local adhesions.  
Arthrofibrosis is a term typically used when the knee scarring is excessive and limiting ROM. 
 
LIFE THREATENING 
The subject is or subject was, in the view of the investigator, at immediate risk of death from the 
adverse event as it occurred. It does not include an adverse event that, had it occurred in a more 
severe form, might have caused death. 
 
LOCAL INFLAMMATION 
A local protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, 
or wall off both the injurious agent and the injured tissues. The classical signs of acute inflammation 
are pain, heat, redness, swelling, and loss of function. http://medical-
dictionary.thefreedictionary.com/systemic+inflammation+response+syndrome+(SIRS) 
 
MISSED ENROLLMENT 
Subjects who do meet inclusion/exclusion criteria but were in the screening process when 
enrollment closed. 
 
NEURALGIA 
Pain in one or more nerves that occurs without stimulation of pain receptor (nociceptor) cells. 
Neuralgia pain is produced by a change in neurological structure or function rather than by the 
excitation of pain receptors that causes nociceptive pain. http://en.wikipedia.org/wiki/Neuralgia 
 
 
 

 
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PATIENT REPORTED OUTCOME MEASURES (PROMS) 
• 
KOOS: The Knee injury and Osteoarthritis Outcome Score (KOOS) Knee Survey is a disease-
specific, measure of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), 
Function in sport and recreation (Sport/Rec) and knee related Quality of life QOL. The last 
week is taken into consideration when answering the questions. KOOS Knee Survey contains 
the full and original version of the Western Ontario and McMasters University Osteoarthritis 
Index (WOMAC) and thus WOMAC scores can be calculated from the KOOS Knee 
questionnaire.  It is estimated to take about 10 minutes to complete the KOOS Knee 
questionnaire. http://www.koos.nu/   
• 
KSS: Knee Society Score87 is a standard clinical evaluation system for reporting results for 
subjects undergoing knee implant surgery and is both subject and physician derived 
(Scuderi et al).  The new Knee Society Scoring System, copyrighted in 2011, is a validated 
system that combines an objective physician-derived component with a subjective patient-
derived component. The objective knee score, completed by the surgeon, includes an 
assessment of alignment, ligament stability, and ROM along with deductions for flexion 
contracture or extensor lag. Given the diverse activity profiles of many contemporary 
subjects, the functional component of the score was improved to include a subject specific 
survey, which evaluates features such as standard activities of daily living, subject-specific 
sports and recreational activities (function), subject satisfaction, and subject expectations. 
Portions of the original Knee Society Clinical Rating System have been integrated into the 
new version to maintain the integrity of the prior version of the Knee Society score. 
• 
SF-12: SF-12® Health Survey is a registered trademark of Medical Outcomes Trust. It is a 
short form of SF-36 in which it is 12 questions from each of the 8 concepts from SF-36 – split 
into physical health and mental health. 
• 
Subject Activity and Satisfaction: Moximed generated questionnaire to capture level of 
subject activity and subject satisfaction post index procedure. 
• 
WOMAC: The Western Ontario and McMaster Universities Arthritis (WOMAC) Index is self-
administered, validated assessment of the three dimensions of pain, disability and joint 
stiffness in knee and hip osteoarthritis using a battery of 24 questions. 
http://www.auscan.org/womac/index.htm 
 
PHYSICIAN REPORTED OUTCOME MEASURES 
• 
KSS: Knee Society Score87 is a standard clinical evaluation system for reporting results for 
subjects  undergoing knee implant surgery and is both subject and physician derived 
(Scuderi et al).  The new KSS survey has recently been validated by the Knee Society. It is 
both physician and subject derived. The objective knee score, completed by the surgeon, 
includes an assessment of alignment, ligament stability, and ROM along with deductions for 
flexion contracture or extensor lag. Subjects then record their VAS score of pain walking on 
level ground and on stairs or inclines satisfaction, functional activities, and expectations. 
Given the diverse activity profiles of many contemporary subjects, the functional 

 
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component of the score was improved to include a subject specific survey, which evaluates 
features such as standard activities of daily living, subject -specific sports and recreational 
activities, subject satisfaction, and subject expectations. Portions of the original Knee 
Society Clinical Rating System have been integrated into the new version to maintain the 
integrity of the prior version of the Knee Society score. 
• 
Pain: Moximed generated questionnaire to capture confounding factors, type, location, and 
scale of pain. 
 
PERONEAL NERVE INJURY 
Damage to the peroneal nerve leading to loss of movement or sensation in the foot and leg. Injury 
may result in a loss of sensation, muscle control, muscle tone, and eventual loss of muscle mass 
because of lack of nervous stimulation to the muscles. 
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001795/ 
 
SCREEN FAILURE 
Subjects who sign informed consent but failed to meet one or more of the Inclusion/Exclusion 
criteria.   
 
SOFT TISSUE IRRITATION 
Superficial Tissue Irritation An inflammatory condition of superficial layers of the skin as a result of 
an aseptic irritant, such as skin reaction to suture or dressings. 
 
Periprosthetic Soft Tissue Irritation An inflammatory condition of the tissues about the implant 
resulting from aseptic tissue irritation. Fluid may accumulate in the periprosthetic tissues possibly 
resulting in the tissue swelling, localized tenderness, pain and/or joint motion is restriction.   
 
SYNOVITIS 
An inflammatory condition of the synovial membrane of the knee joint as the result of aseptic 
trauma, often caused by extreme or excessive activity on the joint. The knee joint is swollen, tender, 
and painful; and motion is restricted 
 
SURGICAL SITE INFECTION90 
Superficial Infection (skin and subcutaneous tissue) occurs after the operation and infection 
involves only skin or subcutaneous tissue of the incision and at least one of the following: 
1. Purulent drainage, with or without laboratory confirmation, from the superficial incision. 
2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the 
superficial incision. 
3. At least one of the following signs or symptoms of infection: pain or tenderness, localized 
swelling, redness, or heat and superficial incision are deliberately opened by surgeon, unless 
incision is culture-negative. 

 
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4. Diagnosis of superficial incisional SSI by the surgeon or attending physician. 
 
Do not report the following conditions as SSI: 
1. Stitch abscess (minimal inflammation and discharge confined to the points of suture 
penetration). 
2. Incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI). 
 
Deep Incisional Infection (deep soft tissue, fascia and muscle) 
Infection occurs if infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision 
and at least one of the following: 
1. Purulent drainage from the deep incision but not from the space component of the surgical 
site. 
2. A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the 
subject has at least one of the following signs or symptoms: fever (>38ºC), localized pain, or 
tenderness, unless site is culture-negative. 
3. An abscess or other evidence of infection involving the deep incision is found on direct 
examination, during reoperation, or by histopathologic or radiologic examination. 
4. Diagnosis of a deep incisional SSI by a surgeon or attending physician. 
 
Notes: 
1. Report infection that involves both superficial and deep incision sites as deep incisional SSI. 
2. Report an organ/space SSI that drains through the incision as a deep incisional SSI. 
 
Organ or Space Infection 
 Infection occurs if no implant is left in place or if implant is in place and the infection appears to be 
related to the operation and infection involves any part of the anatomy (e.g., organs or spaces), 
other than the incision, which was opened or manipulated during an operation and at least one of 
the following: 
1. Purulent drainage from a drain that is placed through a stab wound‡ into the organ/space. 
2. Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space. 
3. An abscess or other evidence of infection involving the organ/space that is found on direct 
examination, during reoperation, or by histopathologic or radiologic examination. 
4. Diagnosis of an organ/space SSI by a surgeon or attending physician. 
 
 

 
Calypso Knee System Clinical Study 
CP0001(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, ECO-3147  EFFECTIVE: 04/01/2021 
 
CONFIDENTIAL 
Page 71 of 71 
Wound infections have been subdivided according to the following clinically related subgroups: 
• 
Aetiology: In a primary infection, the wound is the primary site of infection, whereas a 
secondary infection arises following a complication that is not directly related to the wound; 
• 
Time: An Early infection presents within 30 days of a surgical procedure, whereas an 
infection is described as Intermediate if it occurs between one and three months afterwards 
and Late if it presents more than three months after surgery; 
• 
Severity: a wound infection is described as Minor if there is a discharge without cellulitis or 
deep tissue destruction, and Major if the discharge of pus is associated with tissue 
breakdown, partial or total dehiscence of the deep fascial layers of the wound, or if systemic 
illness is present.