Evaluation of the Calypso Knee System for Symptom Relief in Subjects With Medial Knee Osteoarthritis, OUS
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, OUS 
Short Title: Calypso Knee System Clinical Study, OUS 
Protocol No: CP0002 (Formerly CLIN102918) 
Revision: F 
Study Sponsor 
Moximed, Inc. 
46602 Landing Parkway 
Fremont, CA 94539 
Study Contact 
Alexandra Kraenzlin 
Director Clinical Affairs – Europe 
Moximed, Inc. 
Tel. +41 (44) 515 62 06 
Fax +41 (44) 274 24 59 
E-mail: akraenzlin@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unpublished information contained herein will be published or disclosed without prior written 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: NCT03838978

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 2 of 74 
Investigator Protocol Signature Page 
 
Evaluation of the Calypso Knee System for Symptom Relief in Subjects with Medial Knee 
Osteoarthritis, OUS 
 
Short Title: Calypso Knee System Clinical Study, OUS 
Protocol No: CP0002 (Formerly CLIN102918) 
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) 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 3 of 74 
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 ............................................................................................. 24 
2.0 PROTOCOL ........................................................................................................................ 25 
2.1 
Study Objective .............................................................................................................. 25 
2.2 
Study Scope and Participating Institutions .................................................................... 25 
2.3 
Patient Population ......................................................................................................... 26 
2.4 
Study Endpoints ............................................................................................................. 29 
2.5 
Measures to Increase Validity and Minimize Bias ......................................................... 30 
2.6 
Study Duration ............................................................................................................... 31 
3.0 STUDY PROCEDURES ......................................................................................................... 31 
3.1 
Informed Consent .......................................................................................................... 31 
3.2 
Enrollment Procedure .................................................................................................... 31 
3.3 
Patient Assessments ...................................................................................................... 32 
3.4 
Calypso Knee System Implant Removal ......................................................................... 41 
3.5 
Termination of Subject Participation ............................................................................. 42 
4.0 SAFETY REPORTING ........................................................................................................... 43 
4.1 
Adverse Events ............................................................................................................... 43 
4.2 
Anticipated Adverse Events ........................................................................................... 45 
4.3 
Subsequent Surgical Interventions of the Knee ............................................................. 48 
4.4 
Device Malfunction ........................................................................................................ 49 
4.5 
Device Deficiency ........................................................................................................... 49 
5.0 STATISTICAL ANALYSIS PLAN ............................................................................................. 49 
5.1 
Additional Outcomes ..................................................................................................... 49 
5.2 
Baseline Variables .......................................................................................................... 50 
5.3 
Follow-Up and Reporting ............................................................................................... 50 
6.0 STUDY MANAGEMENT ...................................................................................................... 50 
6.1 
Sponsor Ethical and Regulatory Considerations ............................................................ 50 
6.2 
Investigator Responsibilities .......................................................................................... 53 
6.3 
Clinical Events Committee (CEC) .................................................................................... 56 
6.4 
Medical Monitoring ....................................................................................................... 56 
6.5 
Protocol Deviations ........................................................................................................ 57 
7.0 RISK ANALYSIS ................................................................................................................... 57 
7.1 
Potential Risks ................................................................................................................ 57 
7.2 
Minimizing Study Risks ................................................................................................... 60 
7.3 
Benefit-Risk Summary .................................................................................................... 61 
7.4 
Anticipated Changes during the Investigation ............................................................... 63 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 4 of 74 
8.0 MONITORING PLAN .......................................................................................................... 63 
9.0 REFERENCES ...................................................................................................................... 65 
APPENDIX A:  DEFINITIONS ....................................................................................................... 70 
 
List of Tables 
Table 1 Abbreviations .................................................................................................................... 12 
Table 2 Calypso Knee System Implant Components ...................................................................... 23 
Table 3 Imaging Assessment Schedule .......................................................................................... 34 
Table 4 Calypso Knee System Clinical Study Schedule of Events ................................................... 40 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 6 of 74 
techniques in conjunction with single use, sterile instruments unique to the Calypso 
Knee System.  
Sample Size and 
Number of Sites: 
A total of 80 subjects will be enrolled in this study at up to 14 investigational sites 
located in Europe and in the United States (U.S.). A minimum of 35 subjects will be 
enrolled at up to 7 investigational sites in Europe. 
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 (136kg) 
4. WOMAC pain ≥ 40 (derived from KOOS Knee Survey) 
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 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 7 of 74 
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 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  

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 8 of 74 
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 Survey with a change of ≥10 points  
• 
Clinically significant improvement of at least 20% from baseline on the 
WOMAC function questions in the KOOS Knee Survey 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. 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 9 of 74 
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 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 10 of 74 
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 (Serious) Adverse Device Effect (UADE/USADE) 
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 
CLIN102917: Calypso Knee System Investigator’s Brochure 
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  
CLIN102938: Calypso Clinical Study Informed Consent, OUS (ENG) 
CLIN102852: Calypso Clinical Study Implant Retrieval Protocol 
CLIN102838: Calypso Knee System Rehabilitation Guideline 
CLIN102937: Calypso Clinical Study Investigator Agreement, OUS 
CLIN103113: Statistical Considerations and Preliminary Propensity Score (PS) 
Design Memorandum  
CLIN102839: Calypso Clinical Study Surgeon Training 
CLIN102936: Calypso Clinical Study Monitoring Plan, OUS 
CLIN102859: Calypso Clinical Study CEC Charter 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 11 of 74 
PRINCIPAL CONTACTS 
 
Name, Address and Contact  
Principal Investigator 
 
Study Sponsor Contact 
Alexandra Kraenzlin 
Director Clinical Affairs – Europe  
Moximed, Inc. 
Tel. +41 (44) 515 62 06  
Fax +41 (44) 274 24 59  
E-mail: akraenzlin@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  
 
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 12 of 74 
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 
EC 
Ethics Committee 
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 
MDCG 
Medical Device Coordination Group 
MDD  
Medical Device Directive 
MDR 
Medical Device Regulation 
MEDDEV 
Medical Devices Documents 
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 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 13 of 74 
PP 
Per Protocol Patient Population 
PA 
Posterior-Anterior 
PCU 
Polycarbonate-urethane 
QA 
Quality Assurance 
QOL 
Quality of Life 
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/USADE 
Unanticipated (Serious) 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 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 14 of 74 
 
 
 
 
   
 
Load Bearing and Joint Mechanics 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 15 of 74 
1.1.1 
Current Conservative Care 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Education 
 
 
 
 
Weight loss 
 
 
 
 
 
 
 
 
 
 
 
 
Exercise 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 16 of 74 
 
 
 
Physical Therapy 
 
 
 
 
 
 
  
 
Knee Braces and Orthotics 
 
 
 
 
 
 
 
 
 
Pharmacologic Approaches 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 17 of 74 
 
 
  
 
1.1.2 
Current Surgical Treatment Options  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
High Tibial Osteotomy  
 
 
 
 
 
 
 
 
 
 
    
  
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 18 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
Joint Unloading with External Joint Distraction 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
Knee Arthroplasty 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 19 of 74 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
1.1.3 
Conclusions 
 
 
 
 
  
 
 
 
  
 
1.2 
Rationale for This Study  
 
 
 
 
 
 
 
 
  
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 20 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 21 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
1.3 
Device Name 
 
For purposes of this study, “investigational device” or “study device” refers to the Calypso Knee System. 
 
1.4 
Description of the Device 
 
 
 
 
 
 
 
 
 
  
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 23 of 74 
 
 
   
 
1.4.1 
Mechanism of Action 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
   
 
 
   
 
Table 2 Calypso Knee System Implant Components 
 
 
1.5 
Intended Use Statement 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 24 of 74 
1.6 
Prior Clinical Investigation  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 25 of 74 
2.0 
PROTOCOL  
 
2.1 
Study Objective 
 
The Calypso Clinical study is a 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 14 investigational sites located in 
in Europe and in the U.S. A minimum of 35 subjects will be enrolled at up to 7 investigational sites in Europe. 
 
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. 
 
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 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 26 of 74 
2.3 
Patient Population 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
2.3.1 
Inclusion/Exclusion Criteria 
Radiographic criteria (Inclusion #6 and Exclusion #13, 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 (136kg) 
4. WOMAC pain ≥ 40 (derived from KOOS Knee Survey) 
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  
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 27 of 74 
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 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) 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 28 of 74 
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, endstage 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. 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 29 of 74 
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 Survey with a change of ≥10 points  
• 
Clinically significant improvement of at least 20% from baseline on the WOMAC function questions 
in the KOOS Knee Survey 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) 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 30 of 74 
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 
• 
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  
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 31 of 74 
• 
 
 
  
 
 
 
 
 
  
 
 
 
 
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. It is 
anticipated that it will take approximately 6 months to enroll a minimum of 35 subjects in Europe. The 
overall study duration, including enrollment and completion of the 5 year follow-up, is approximately 5.5 
years.  
 
3.0 
STUDY PROCEDURES 
 
3.1 
Informed Consent  
 
 
 
  
 
 
 
 
 
 
 
   
 
3.2 
Enrollment Procedure  
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 32 of 74 
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
3.3 
Patient Assessments 
3.3.1 
Patient Screening (Pre-Op Visit) 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
  
 
 
 
 
 
   
  
  
 
 
 
 
 
 
 
  
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 33 of 74 
• 
• 
• 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 34 of 74 
Table 3 Imaging Assessment Schedule 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 35 of 74 
3.3.2 
Surgical Procedure  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Procedures 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
  
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 36 of 74 
• 
 
 
 
 
 
3.3.3 
Concomitant Procedures 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
3.3.4 
Post Procedure Care (Discharge) 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 38 of 74 
3.3.6.2 3 and 6 month Follow-Up (±31 days) 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
3.3.6.3 1 year, 18 months, 2, 3, 4, and 5 Year Follow-up (± 60 days) 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 

 
 
Calypso Knee System Clinical Study, OUS 
 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 39 of 74 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 42 of 74 
3.5 
Termination of Subject Participation 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
All subjects who undergo implantation with the Calypso Knee System will be followed for 60 months (5 
years) post-procedure. All explanted subjects including those converted to arthroplasty will continue to be 
followed for the remainder of the 5 year study. Anticipated reasons for early termination of subject 
participation include: 
 
• 
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 Withdrew 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. 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 43 of 74 
4.0 
SAFETY REPORTING 
 
 
 
 
 
  
 
4.1 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
  
 
The Investigator, on the basis of his or her clinical judgment, will determine the relationship of the AE to 
the device and/or procedure based on the following categories: 
 
1. Unrelated: The adverse event is determined to be solely caused by the underlying disease, disorder 
or condition of the subject, or attributable solely to other extraneous causes (unrelated to the device, 
device malfunction, or the procedure). 
2. Possibly related: The adverse event has onset within a clinically relevant temporal relationship to 
exposure to the device or procedure, and is plausibly at least partially caused by or aggravated by 
the use of the device, device malfunction, or the procedure. It must also meet one of the following 
criteria: (1) follows a known or easily foreseen pattern of response to device use or procedure and 
(2) is not fully attributable to the underlying disease, disorder or condition of the subject, or 
attributable to other extraneous causes. 
3. Probably related: The adverse event has onset within a clinically relevant temporal relationship to 
exposure to the device or procedure, and is more likely than not to be at least partially caused by or 
aggravated by the use of the device, device malfunction, or the procedure. It must also meet both of 
the following criteria: (1) follows a known or easily foreseen pattern of response to device use or 
procedure; and (2) is not fully attributable to the underlying disease, disorder or condition of the 
subject, or attributable to other extraneous causes. In addition, if the adverse effect is reversible 
upon reoperation or device exchange, and such a procedure is done, the effect disappears or lessens 
in severity within the expected time interval. 
4. Definitely related: The adverse event is clearly caused by the use of the device, device malfunction, 
or the procedure. It must meet all following criteria: (1) has a clear temporal relationship between 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 49 of 74 
• 
Other interventions: This category includes other surgeries of the study knee that the subject 
incurs while enrolled in the study that seemingly are unrelated to the implanted device.  
 
4.4 
Device Malfunction 
 
All device malfunctions of the Calypso Knee System must be reported within 24 hours of the knowledge of 
the event in the EDC system.   
 
4.5 
Device Deficiency 
 
 
 
 
 
  
 
5.0 
STATISTICAL ANALYSIS PLAN 
 
Refer to the Statistical Considerations and Preliminary Propensity 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 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 50 of 74 
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 
 
 
 
 
 
  
 
 
  
 
 
 
  
 
6.0 
STUDY MANAGEMENT  
 
6.1 
Sponsor Ethical and Regulatory Considerations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
   
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 51 of 74 
Selection of Clinical Sites 
 
 
 
 
 
 
 
 
 
 
Site Training 
 
 
 
 
 
 
 
 
 
Investigator Training 
 
 
 
 
 
 
 
 
 
 
 
Subject Confidentiality 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 52 of 74 
 
 
 
 
 
Data Management 
 
 
 
   
 
Record Retention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Liability and Insurance Conditions 
 
 
 
 
 
 
Publication Policy  
 
 
 
 
 
  
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 53 of 74 
6.2 
Investigator Responsibilities 
 
 
 
 
 
 
 
 
 
 
 
 
6.2.1 
IRB Approval and Informed Consent 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
6.2.2 
Data Collection and Reporting 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 54 of 74 
 
 
 
 
 
 
 
 
6.2.3 
Data Completion and Submission 
 
 
 
 
 
  
 
6.2.4 
Device Accountability 
 
 
 
  
 
6.2.5 
Source Documents 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 55 of 74 
6.2.6 
Regulatory Filing 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 56 of 74 
6.2.7 
Audits/Inspections 
 
 
 
 
6.3 
Clinical Events Committee (CEC) 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
6.4 
Medical Monitoring 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 57 of 74 
6.5 
Protocol Deviations 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
7.0 
RISK ANALYSIS  
 
7.1 
Potential Risks 
 
 
 
 
 
  
 
Surgical Risks 
 
There are risks related to any surgical procedure as well as procedures specific to surgical intervention of 
the knee. Surgical risks associated are described below.   
 
1. Risks associated with general surgery include:  
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 58 of 74 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2. Risks associated with knee surgery include:  
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 59 of 74 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
 
 
 
3. Risks associated with Calypso Knee System:   
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 60 of 74 
• 
 
 
  
 
 
 
 
 
 
 
 
 
   
 
Risks Associated with Radiographs 
 
 
 
 
 
 
Risks Associated with MRI 
 
 
 
 
 
 
 
Reproductive Risks 
 
  
 
Blood Draw Risks 
 
 
Allergy Risks 
 
 
7.2 
Minimizing Study Risks 
 
 
 
 
 
 
 
 
 
  

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 61 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
   
 
 
  
 
 
 
 
 
 
 
 
7.3 
Benefit-Risk Summary 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
   
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 62 of 74 
 
 
 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 63 of 74 
 
 
  
 
 
 
  
 
 
 
 
 
 
  
 
7.4 
Anticipated Changes during the Investigation 
There are no known anticipated changes of the Calypso Knee System during the investigation.  
 
8.0 
MONITORING PLAN 
 
 
 
 
 
 
 
 
 
 
  
 
Site Qualification/Initiation Visits 
  
 
 
 
 
 
 
  
 
Interim Monitoring Visits 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 64 of 74 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
Site Close Out Visit 
 
 
 
 
  
 
Qualifications of Study Monitor 
 
 
  
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 65 of 74 
9.0 
REFERENCES  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 66 of 74 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
 
 
 
 
 
 
 
 
 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 70 of 74 
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 DEFICIENCY 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance. NOTE: Device deficiencies include malfunctions, use errors and inadequate labeling. 
 
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).  
 
ENROLLED 
Subjects who sign informed consent and undergo an anesthesia start time for purposes of receiving the 
Calypso Knee System. 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 71 of 74 
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 
 
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 new 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 72 of 74 
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 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 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/ 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 73 of 74 
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 is deliberately opened by surgeon, unless incision is 
culture-negative. 
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. 
 
 

 
Calypso Knee System Clinical Study, OUS 
CP0002(F) CALYPSO KNEE SYSTEM CLINICAL STUDY PROTOCOL, OUS, ECO-3232 EFFECTIVE: 02/02/2022 
CONFIDENTIAL 
Page 74 of 74 
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. 
 
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.