A Prospective Study to Evaluate the ConforMIS iTotal® (CR) Knee Replacement System and iPoly XE Tibial Inserts
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: Restor3D

 
 
A Prospective Study to Evaluate the ConforMIS 
iTotal® (CR) Knee Replacement System and iPoly 
XE Tibial Inserts 
 
Protocol 16-001 
 30 Jun 2016 
(NCT03289754) 
 
 
SPONSOR: 
ConforMIS, Inc. 
600 Technology Park Drive, Billerica, MA 01821 
 
Contact: 
Marc Quartulli, Vice President, Clinical Affairs 
Ph: 781.345.9191 
marc.quartulli@conformis.com 
 
 
ConforMIS internal use:  CD-00027 v1.0 AA 
 
 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 2 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
 
 
 
A Prospective Study to Evaluate the ConforMIS 
iTotal® (CR) Knee Replacement System and 
iPoly XE Tibial Inserts 
 
 
Protocol Number: 16-001 Version 1.0 AA 
Date:  30 June 2016 
Contact:  Marc Quartulli 
 
      Vice President Clinical Affairs 
 
      781.345.9191 
                Marc.quartulli@conformis.com 
 
 
Protocol Signature Page 
This is to acknowledge that I have received the above-identified protocol, that I 
have read and understood its content, and that I agree to conduct the clinical trial 
in accordance with the procedures outlined therein. 
 
 
Investigator Approval: 
 
 
 _____________________________________ 
                                     Signature 
 
 
 
 
Date 
 
 
                                _____________________________________ 
                                     Print Name 
 
 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 3 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
 
Table of Contents 
 
1. 
INTRODUCTION, BACKGROUND & OBJECTIVE ........................................... 4 
2. 
DEVICE DESCRIPTION ........................................................................................ 4 
3. 
STUDY DESIGN..................................................................................................... 5 
4. 
STUDY DURATION .............................................................................................. 5 
5. 
STUDY ENDPOINTS ............................................................................................. 5 
5.1. 
Primary Endpoint ................................................................................................. 5 
5.2. 
Secondary Endpoints ............................................................................................ 5 
6. 
INCLUSION AND EXCLUSION CRITERIA ....................................................... 5 
6.1. 
Inclusion Criteria .................................................................................................. 5 
6.2. 
Exclusion Criteria ................................................................................................. 6 
7. 
SITE SELECTION .................................................................................................. 6 
8. 
ENROLLMENT ...................................................................................................... 7 
9. 
SCHEDULE OF EVALUATIONS BY VISIT........................................................ 7 
9.1. 
Pre-operative Visit (Up to 4 months prior to Surgery) ............................................ 7 
9.2. 
Surgery Visit (Day 0) ............................................................................................... 8 
9.3. 
6-Week Follow-up Visit (± 2 weeks) ....................................................................... 8 
9.4. 
6-Month follow-up visit (± 3 weeks) ....................................................................... 9 
9.5. 
Year 1, 2, and 5 Follow-up Visits (± 2 months) ...................................................... 9 
9.6. 
Year 3, 4, 6, 7, 8, and 9 Follow-up Visits (± 3 months) .......................................... 9 
9.7. 
Year 10 Follow-up Visit (± 4 months) ................................................................... 10 
9.8. 
Early Termination Visit ......................................................................................... 10 
10. 
SAFETY REPORTING ......................................................................................... 10 
11. 
DATA MANAGEMENT....................................................................................... 12 
12. 
MONITORING ...................................................................................................... 12 
13. 
STATISTICAL METHODS .................................................................................. 12 
14. 
SUBJECT PROTECTION ..................................................................................... 13 
15. 
ETHICAL CONSIDERATIONS ........................................................................... 13 
16. 
REPORTS .............................................................................................................. 14 
17. 
LITERATURE ....................................................................................................... 14 
18. 
APPENDIX A – Schedule of Evaluations ............................................................. 15 
 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 4 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
1. INTRODUCTION, BACKGROUND & OBJECTIVE 
 
Osteoarthritis or other degenerative changes or injury can cause damage to the structures in the 
knee, causing pain and discomfort, and lessening the quality of life.  Knee replacement, or knee 
arthroplasty, is a common surgical procedure performed to relieve the pain and disability 
resulting from osteoarthritis. In general, the surgery consists of replacing the diseased or damaged 
joint surfaces of the knee with metal and plastic components shaped to allow continued motion of 
the knee. 
 
Today, over 600,000 patients undergo total knee replacement each year in the United States, a 
number that is projected to increase greatly over the next 20 years (Kurtz).  Total knee 
replacement has been performed since 1964 and has been shown to be an effective, long-lasting 
procedure with good survivorship of the implants for patients with osteoarthritis.  Despite, the 
excellent survivorship, there are still a significant percentage of patients that remain dissatisfied 
with their results.  Studies report 14-39% of patients report some level of dissatisfaction with their 
knees post-surgically (Noble et al., Bourne et al., Suda et al.). 
 
The iTotal CR total knee replacement system and iPoly XE have been cleared by the FDA and 
CE marked for the treatment of osteoarthritis (OA).  This study is designed to evaluate the 
clinical outcomes of subjects who have recently undergone surgery with the iTotal® Cruciate 
Retaining (CR) Total Knee Replacement System (KRS) who have also had iPoly XE Tibial 
Inserts implanted. 
2. DEVICE DESCRIPTION 
 
The iTotal® CR KRS is a tri-compartmental semi-constrained knee prosthesis composed of three 
components: a Femoral Component, a Tibial Component, and a Patellar Component. The product 
design incorporates a bone preserving approach for the treatment of severe pain and/or disability 
of a knee damaged by osteoarthritis or trauma. It is intended for use in those patients whose 
condition cannot be appropriately or effectively addressed using a device that treats only one or 
two compartments of the knee (i.e. a unicompartmental, bicompartmental, or patellofemoral 
prosthesis).  
 
Using patient imaging, a patient-specific implant is designed that best meets the geometric and 
anatomic requirements of the specific patient. The treatment allows for the placement of a 
cemented metallic device designed from the patient’s natural bone geometry. This process allows 
definition of the shape and size of the femoral and tibial components of the implant, as well as the 
disposable instrumentation (Fitz).  
 
The iTotal® CR knee is constructed of cobalt chrome and conforms to the surface of the patient's 
femoral condyle, replacing the damaged cartilage with a smooth articulating surface. Specifically, 
the femoral component and tibial tray are manufactured from cobalt chromium molybdenum 
alloy. The tibial insert being utilized in this study will be a highly-crosslinked, Vitamin-E 
enriched UHMWPE (iPoly XE). 
 
Several key features of the iTotal are listed below. 
• 
Minimally traumatic procedure 
• 
Precise fit to ensure range of motion without impingement or overhang 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 5 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
• 
Complete cortical rim coverage 
• 
Anatomic component alignment 
• 
Disposable, patient-specific instrumentation 
• 
Simple, reproducible surgical technique 
• 
Potential for less post-operative pain and shorter post-operative recovery time 
3. STUDY DESIGN 
 
The study is prospective and single-center. Subjects will be implanted with an iTotal® CR Knee 
Replacement System in conjunction with an iPoly XE insert.  The study will include a minimum 
of 50 subjects and a maximum of 60 subjects at a single center. The study site will be located in 
Germany.   
4. STUDY DURATION 
 
The study subjects will be followed for 10 years post implant. The follow-up visit schedule will 
include on-site visits at 12 weeks, 6 months, 1 year, 2 years, 5 years and 10 years post implant to 
follow the surgeon’s normal standard of practice.  At 3, 4, 6, 7, 8, and 9 years post-op data may 
be collected; these data can be collected via phone call/email and do not require a subject to visit 
the site. 
5. STUDY ENDPOINTS 
 
5.1. Primary Endpoint 
The study primary endpoint is pain and function at 1 Year after implantation, as measured by: 
1. Knee Society Clinical Rating Score 
1.1. Objective Knee Score 
1.2. Function Score 
1.3. Satisfaction Score 
1.4. Expectation Score 
 
5.2. Secondary Endpoints 
The study secondary endpoints are: 
1. The Knee Injury and Osteoarthritis Outcome Score (KOOS) 
2. Revision rates post-implantation 
3. Incidence of major procedure–related and device-related complications including 
infection rate 
4. Post-operative limb alignment if long leg x-rays available 
5. Radiographic loosening, radiolucencies 
6. Length of procedure 
7. Length of hospital stay in hours (admission to discharge) 
8. Blood loss during surgery & blood transfusion rates 
6. INCLUSION AND EXCLUSION CRITERIA 
 
6.1. Inclusion Criteria 
1. Clinical condition included in the approved Indications For Use for the iTotal® CR 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 6 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
2. Osteoarthritis, as confirmed by the investigator’s assessment of disease status at 
screening visit that warrants a TKR procedure. Disease status is assessed by Clinical 
and Radiographic assessment. 
3. Willingness to participate in the clinical study, to give informed consent, and to 
attend all follow-up visits 
4. > 18 years of age 
 
6.2. Exclusion Criteria 
1. Simultaneous bilateral procedure required 
2. BMI > 40 
3. Active malignancy (defined as a history of any invasive malignancy – except non-
melanoma skin cancer), unless patient has been treated with curative intent and there 
have been no clinical signs or symptoms of the malignancy for at least 5 years 
4. Poorly controlled diabetes 
5. Neuromuscular conditions which prevent patient from participating in study activities 
6. Active local or systemic infection 
7. Immunocompromised 
8. Fibromyalgia or other general body pain related condition 
9. Rheumatoid arthritis or other forms of inflammatory joint disease 
10. Loss of bone or musculature, osteonecrosis, neuromuscular or vascular compromise 
in the area of the joint to be operated on, to an extent that the procedure is unjustified 
11. Diagnosed with or receiving treatment for Osteoporosis 
12. Other physical disability affecting the hips, spine, or contralateral knee 
13. Severe instability due to advanced loss of osteochondral structure 
14. Prior arthroplasty of the affected knee, including High Tibial Osteotomy (HTO) 
15. Compromised PCL or collateral ligament 
16. Severe fixed valgus or varus deformity of  >15º 
17. Extensor lag > 15º 
18. Fixed flexion contracture ≥ 15º 
19. Unwilling or unable to comply with study requirements 
20. Participation in another clinical study which would confound results 
21. Allergy to any of the implant materials 
 
7. SITE SELECTION 
 
The site will be selected by a Site Selection Committee based on a set of defined criteria. The 
Site Selection Committee will be led by Clinical Affairs. The site selection criteria includes, 
but is not limited to: 
• 
Interest in participating in the study as demonstrated by responsiveness 
• 
Demonstrated technical and surgical skills with iTotal® CR device - Investigator must 
have completed a cadaver training at minimum prior to enrolling their first patient 
• 
Sufficient patient volume to expect timely subject enrollment 
• 
Ability to adhere to the standards of Good Clinical Practice (GCP) and Good 
Documentation Practice (GDP) 
• 
Clinical study experience and resources that demonstrate good compliance with study 
requirements and timely, complete documentation of subject follow-up 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 7 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
• 
Willingness to allow personnel from ConforMIS (or its designee) access to the 
hospital records, Investigator’s study records, data, and patient files as they pertain to 
the study 
8. ENROLLMENT 
 
Potential subjects are identified by the Investigator or study staff based on patients’ clinical 
and radiographic assessments during regular medical care. The Investigator or study staff 
provides study information and the approved Informed Consent Form to potential subjects 
and answers any questions. Once the patient signs the consent form, they are assigned a 
unique subject identification number through the EDC system that is comprised of a five digit 
number starting with a two digit site number assigned by ConforMIS at the Site Initiation 
followed by a three digit subject number, assigned chronologically for the entire study. For 
example, at site 01, the first subject enrolled will receive number 01-001, followed by 01-
002, 01-003, etc. 
 
The Investigator and/or study staff assesses the subject against the Inclusion and Exclusion 
criteria to determine eligibility. Eligibility includes clinical assessments, radiographic 
assessments and a review of the subject’s medical history. The radiographic assessments 
should include: 
1. Knee x-ray 3 views – AP, lateral, sunrise or Merchant 
2. If site has the technology, three-foot standing x-ray (full length, full weight bearing 
film) – AP view 
 
If the subject is not eligible to participate in the study, the subject is not enrolled and is 
considered a screen failure. All screen failures are tracked by the site manually in a tracking 
spreadsheet and electronically in a clinical database. Patient identification numbers for screen 
failures are not to be re-used. 
 
The following Case Report Forms are required for all screen failures: 
• 
SUBJECT INFORMATION 
• 
INCUSION/EXCLUSION CRITERIA 
 
If the subject is eligible to participate in the study, the subject is enrolled. 
 
9. SCHEDULE OF EVALUATIONS BY VISIT 
 
A table displaying the Schedule of Evaluations is in Appendix A.  Enrolled subjects will 
complete each visit in the schedule of evaluations. 
9.1. Pre-operative Visit (Up to 4 months prior to Surgery) 
Many of the screening assessments required to ensure subject eligibility are also considered 
the pre-operative assessments. The results of the assessments are captured on the following 
Screening/Pre-operative Case Report Forms: 
• 
SUBJECT INFORMATION 
• 
INCLUSION/EXCLUSION CRITERIA 
• 
MEDICAL HISTORY 
• 
PAIN MEDICATIONS 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 8 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
• 
CONCOMITANT MEDICATIONS 
• 
KNEE SOCIETY SCORE (Surgeon portion) 
 
 
The subject completes the following questionnaires to assess pain and function as part of their 
pre-operative assessment: 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject portion) 
 
X-rays: 
• 
3 views – AP, lateral, sunrise or Merchant 
• 
Three-foot standing x-ray (full length, full weight-bearing film): AP view 
9.2. Surgery Visit (Day 0) 
The Investigator surgically implants the iTotal® CR and iPoly XE inserts in compliance with 
the ConforMIS surgical training and iTotal® CR Instructions for Use. 
 
The site completes the following Case Report Forms: 
• 
SURGICAL SUMMARY 
• 
DISCHARGE SUMMARY 
• 
PAIN MEDICATIONS (update if changes have occurred) 
• 
CONCOMITANT MEDICATIONS (update if changes have occurred) 
• 
ADVERSE EVENTS / SERIOUS ADVERSE EVENTS (if any occur during surgery 
through discharge from hospital) 
 
X-rays: None 
9.3. 12-Week Follow-up Visit (± 2 weeks) 
 
At the 12-week follow-up visit, the Investigator or study staff performs a post-operative 
knee assessment and identifies any adverse events that have occurred since the subject was 
discharged from the hospital. 
 
The site completes the following Case Report Forms: 
• 
FOLLOW-UP FORM 
• 
KNEE SOCIETY SCORE (Surgeon portion)  
• 
PAIN MEDICATIONS (update if changes have occurred) 
• 
CONCOMITANT MEDICATIONS (update if changes have occurred) 
• 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject completes the following questionnaires to assess post-operative pain and 
function: 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject portion) 
 
X-rays: 
• 
3 views – AP, lateral, sunrise or Merchant 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 9 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
• 
Three-foot standing x-ray (full length, full weight-bearing film): AP view 
9.4. 6-Month follow-up visit (± 3 weeks) 
At the 6-month follow-up visit, the Investigator or study staff performs knee assessments and 
identifies any adverse events that have occurred since the last visit. 
 
The site completes the following Case Report Forms: 
• 
FOLLOW-UP FORM 
• 
KNEE SOCIETY SCORE (Surgeon portion) 
• 
PAIN MEDICATIONS (update if changes have occurred) 
• 
CONCOMITANT MEDICATIONS (update if changes have occurred) 
• 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject completes the following questionnaires to assess post-operative pain and 
function: 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject portion) 
 
X-rays: None 
9.5. Year 1, 2, and 5 Follow-up Visits (± 2 months) 
At the 1-year, 2-year and 5-year follow-up visits, the Investigator or study staff performs a 
knee assessment and identifies any adverse events that have occurred since the subject’s last 
visit. 
 
The site completes the following Case Report Forms: 
• 
FOLLOW-UP FORM 
• 
KNEE SOCIETY SCORE (Surgeon portion) 
• 
PAIN MEDICATIONS (update if changes have occurred) 
• 
CONCOMITANT MEDICATIONS (update if changes have occurred) 
• 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The subject completes the following questionnaires to assess post-operative pain and 
function: 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject portion) 
 
X-rays: Optional  
9.6. Year 3, 4, 6, 7, 8, and 9 Follow-up Visits (± 3 months) 
On the anniversary of the implant surgery for years 3, 4, 6, 7, 8, and 9, the Investigator or 
study staff assesses the subject for complications or adverse events, and specifically to 
determine if the iTotal® CR has been revised. It is not necessary for the subject to go to the 
clinic for a visit, as the site can obtain the data via direct communication with the subject 
(such as via telephone or email). 
 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 10 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
The site completes the following Case Report Form: 
• 
FOLLOW-UP FORM 
• 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
X-rays: None 
9.7. Year 10 Follow-up Visit (± 4 months) 
On the 10-year anniversary of the implant surgery, the Investigator or study staff assesses the 
subject to determine if the iTotal® CR has been revised. 
 
The site completes the following Case Report Form: 
• 
FOLLOW-UP FORM 
• 
PAIN MEDICATIONS 
• 
CONCOMITANT MEDICATIONS 
• 
ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
• 
KNEE SOCIETY SCORE (Surgeon portion) 
• 
SUBJECT DISPOSITION 
 
The subject is asked to complete the following questionnaires to assess long term post-
operative pain and function. Note that the subject should return to the clinic to complete these 
questionnaires.  If a return to the clinic is not possible the patient will be provided the 
questionnaires either via mail, email, or through an internet site. 
 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject portion) 
 
X-rays: Optional 
9.8. Early Termination Visit 
In the event that the study subject ends their participation in the study prior to the 10-year visit, 
the investigator or designated study staff will complete the following CRFs: 
• 
SUBJECT DISPOSITION 
• 
PAIN MEDICATIONS 
• 
CONCOMITANT MEDICATIONS 
• 
ADVERSE EVENTS / SERIOUS ADVERSE EVENTS (if any) 
o REVISION FORM (if necessary) 
 
The Investigator or designated study staff will make every attempt to complete the following 
CRFs (for both knees if necessary): 
• 
THE KNEE INJURY AND OSTEOARTHRITIS OUTCOME SCORE (KOOS) 
• 
KNEE SOCIETY SCORE (Subject and Surgeon portions) 
 
10. SAFETY REPORTING 
 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 11 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
All Adverse Events (AEs) are recorded by the site from the day of surgery on the Adverse Event 
CRF and should be reported within 5 days of site becoming aware of the event. In addition, all 
Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) must be 
reported to ConforMIS or designee via telephone or email as soon as possible once discovered by 
the site. SAEs should be reported to ConforMIS within 3 working days, and UADEs should be 
reported to ConforMIS within 2 working days. The Investigator and investigative site will also be 
responsible for required reporting to the site’s Institutional Review Board/Independent Ethics 
Committee (IRB/IEC). 
 
For the purposes of this protocol, only those AEs categorized as Possible, Probable or Definite in 
relationship to the devices will be recorded.  Those events that are Unlikely or Not Related to the 
device will not be collected.  All Serious Adverse Events (SAEs) will be recorded regardless of 
the relationship to the device.  Please see definitions below.  
 
ConforMIS will be responsible for safety reporting as required by local regulations.  
 
Adverse Event: Any untoward or unfavorable medical occurrence associated with the use of a 
medical product in a human patient, including any abnormal sign, symptom, or disease.  Report 
only those AEs with Possible or above, relationship. 
 
Definite: 
Clear-cut temporal association and no other possible cause. 
Probable: 
Clear-cut temporal association and a potential alternative etiology is 
not apparent. 
Possible: 
Temporal association is less clear and other etiologies are also 
possible. 
Unlikely: 
Temporal association and the nature of the event is such that the 
study device is not likely to have had any association with the 
observed event (cause and effect relationship improbable but not 
impossible). 
Not Related: 
There is no temporal association and/or evidence exists that the 
event is definitely related to another etiology. 
 
Serious Adverse Event: Any undesirable experience associated with the use of a medical product 
in a patient in which the patient outcome is: death, a life-threatening event, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant 
disability/incapacity, a congenital anomaly/birth defect or requires intervention to prevent 
permanent impairment or damage. 
Unanticipated Adverse Device Effect (21 CFR 812.3): Any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of patients. 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 12 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
11. DATA MANAGEMENT 
 
Each site is responsible for accurate, complete, and timely collection/recording of data using the 
CRF (or EDC system) provided. Data will be stored in a validated and secure database for analysis. 
ConforMIS will periodically review all data, and specifically adverse event data to determine 
interim revision rates, frequency of serious adverse device effects and subject outcomes. If missing 
data fields or incorrect data are identified, the site may be contacted to provide the missing/correct 
data. ConforMIS or a designee will provide Case Report Forms (paper and/or electronic) to the 
study sites, along with access to the EDC system. 
 
12. MONITORING 
 
ConforMIS or designee will monitor clinical sites to review source data, study conduct, and 
compliance to the protocol. Each site will be monitored shortly after beginning enrollment to ensure 
early identification and resolution of any issues. After the initial monitoring visit, the site will be 
monitored at a frequency determined by ConforMIS or designee based on a variety of variables 
including, but not limited to, the rate of enrollment, the number of issues identified that require 
follow-up, changes in site personnel, etc. 
13. STATISTICAL METHODS 
 
All statistical processing will be performed using SAS® Version 9.2 or later unless otherwise stated.  
Efficacy analyses performed using the intent-to-treat (ITT) population will be considered primary.  
Safety analyses will be performed on the safety population. 
 
No imputations will be made for missing observations.  Continuous variables will be summarized 
with sample size, mean, standard deviation, median, minimum, maximum, and 95% confidence 
intervals, as appropriate.  Categorical variables will be summarized with frequency counts, 
percentages, and 95% confidence intervals, as appropriate. 
 
Populations 
The safety population will be comprised of all subjects for whom the procedure is initiated. 
 
The ITT population will be comprised of all subjects for whom the procedure is completed. 
 
Demographic and Baseline Evaluations 
Demographic variables (age, gender, ethnicity, and race) will be recorded in the eCRF and 
summarized using descriptive statistics.   
 
Efficacy Analysis 
 
Primary Efficacy Analysis 
There is one primary endpoint, change from baseline to 1-Year in KSS.  Hypothesis testing 
of the primary endpoints will be conducted for the ITT population, and will be analyzed 
with paired t-test.     
 
Secondary Efficacy Analyses 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 13 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
Secondary endpoints will be analyzed for the ITT population.  Details of statistical testing 
for each endpoint will be further discussed in the Statistical Analysis Plan.  
 
1. Change from baseline in KSS at years 2, 5 and 10 post-implantation 
2. Change from baseline in KOOS at years 1, 2, 5 and 10 post-implantation 
3. Post-operative limb alignment if long leg x-rays available 
4. Length of hospital stay in hours (admission to discharge) 
5. Blood loss during surgery  
6. Transfusion rate 
 
Supportive Efficacy Endpoints 
1. Revision rates post-implantation  
2. Radiographic loosening, radiolucencies 
3. Length of procedure: Skin to Skin 
 
Safety Analysis 
All adverse events (AEs) occurring during the study will be recorded and classified. For the 
safety population, all reported AEs will be summarized by the number of subjects reporting AEs, 
severity, relationship to procedure, relationship to device, and seriousness. For summaries of AEs 
by relationship or severity, each subject will be counted only once using the event with the 
greatest relationship or highest severity. 
 
In addition to overall AE summaries, AEs will be summarized for the following study periods: 
• 
Day of procedure to 6 months post procedure 
• 
Annual summaries (1 Year, 2 Year, etc.) from day of procedure 
 
Serious adverse events (SAEs) will be summarized by group, severity, relationship to procedure, 
and relationship to device.  SAEs will also be listed by subject. 
 
All information pertaining to AEs noted during the study will be listed by subject. 
 
Sample Size Determination 
The sample size for this study was not based on a power analysis.  However, a sample size of up 
to 50 subjects is considered to provide adequate estimation of the study endpoints. 
14. SUBJECT PROTECTION 
 
Data will be de-identified on forms and in the clinical database, and subjects will be identified 
only by a code or subject number. All information and data sent to ConforMIS or designee 
concerning subjects or their participation in this study will be considered confidential, and 
confidentiality shall be observed by all parties involved at all times during the study. All data 
used in analysis and reports will be used without identifiable reference to the subject. All data 
will be secured against unauthorized access. The Investigator and investigative site will be 
responsible for compliance with all local privacy regulations.  
15. ETHICAL CONSIDERATIONS 
 
The protocol and Informed Consent Form must be approved by a central IRB or the IRB/IEC for 
the institution where the study is conducted. Each subject shall give informed consent in a form 

ConforMIS, Inc. 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 14 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
and manner that meets all IRB/IEC requirements. All patients must be informed that the device is 
available commercially and that participation in the clinical study is not required for them to be 
treated with the device.  Investigators shall agree to conduct the study in compliance with the 
provisions of the Declaration of Helsinki and with ICH/GCP Standards. 
 
In compliance with the Food and Drug Administration Amendments Act of 2007 (FDAAA), this 
study will be listed in www.clinicaltrials.gov. 
16. REPORTS 
 
A final study report shall be prepared and provided to all investigative sites for submission to 
their IRB/IEC.  The final study report will be made a permanent record in the ConforMIS 
document control system.  
17. LITERATURE 
 
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of Primary and Revision Hip and Knee 
Arthoplasty in the United States from 2005 to 2030. J Bone Joint Surg Br. 2007;89:780-85. 
 
Rougraff BT, et. al. A comparison of tricompartmental and unicompartmental arthroplasty for the 
treatment of gonarthrosis. Clin Orthop Relat Res. 1991; 273:157–164. 
 
Data on File, ConforMIS. 
 
Fitzpatrick C, FitzPatrick D, Lee J, Auger D. Statistical design of unicompartmental tibial 
implants and comparison with current devices. Knee. 2007;14:138-44. 
 
Fitz W. Unicompartmental Knee Arthroplasty with Use of Novel Patient-Specific Resurfacing 
Implants and Personalized Jigs. J Bone Joint Surg Am. 2009;91:69-76. 
 
Bourne RB, et.al. Patient satisfaction after total knee arthroplasty: Who is satisfied and who is 
not?. Clin Orthop Relat Res (2010) 468:57–63. 
 
Noble PC, et al. The John Insall Award: Patient expectations affect satisfaction with total knee 
arthroplasty. Clin Orthop Relat Res. 2006;452:35–43.

 
ConforMIS, Inc. 
Protocol 12-001 Version 6.0 AD 
 21 August 2014 
 Page 15 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
18.  APPENDIX A – Schedule of Evaluations 
Evaluation 
Screening/ 
Pre-Op 
Surgery 
& 
Discharge 
12 Week 
Follow-up 
6 Month 
Follow-up  
Year 1, 2, 5  
Follow-up 
Year 3, 4, 6, 
7, 8, 9 
Follow-up 
Year 10 
Follow-up 
Visit window 
Up to 4 
months 
prior to 
surgery 
- 
± 2 weeks 
± 3 weeks 
± 2 months 
± 3 months 
± 4 months 
Subject Information 
X 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Pain Medications 
X 
X 
X 
X 
X 
 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
 
X 
Knee Society Score^ 
X 
 
X 
X 
X 
 
X 
Radiographic Evaluation* 
X 
 
X 
 
O 
 
O 
Knee Injury & Osteoarthritis 
Outcome Score (KOOS)^ 
X 
 
X 
X 
X 
 
X 
Surgical & Discharge 
Summary 
 
X 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
Follow-Up 
 
 
X 
X 
X 
X 
X 
X=Protocol mandated tests; O=Optional tests  
^KSS & KOOS Questionnaires should be completed for ALL iTotal knees and on the contralateral knee if the contralateral knee has previously 
had standard TKA performed. 
*Radiographic Evaluation includes: 
1. Knee x-ray 3 views – AP, lateral, sunrise or Merchant 
2. If available, three-foot standing x-ray (full length film with full weight bearing) – AP view 

 
ConforMIS, Inc. 
 
 
 
Protocol 16-001 Version 1.0 AA 
30 June 2016 
 Page 16 of 16 
Confidential and Proprietary 
Nothing herein is to be disclosed without the prior express written permission of ConforMIS, Inc. 
PROTOCOL HISTORY 
 
Protocol 
Version 
Protocol Date 
Updated by: 
Changes Made: 
1.0 
30 June 2016 
Marc Quartulli 
Initial release