Zimmer Knee Creations SCP® Observational Cohort Follow-Up Study
Conditions: Bone Marrow Edema
Sponsor: Zimmer Biomet

 
Clinical Investigational Plan 
 
 
 
Zimmer Knee Creations SCP® Observational 
Cohort Follow-Up Study 
 
 
 
 
 
 
 
 
 
 
 
Version 2: August 24, 2016 
 
 
 
Sponsor: 
Zimmer Knee Creations 
805 Springdale Drive 
Exton, PA 19341 
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1. 
Protocol Synopsis 
Study Title 
Zimmer Knee Creations SCP® Observational Cohort Follow-Up 
Study 
Study Nickname 
SCP® Observational Study 
Study Design 
Multi-center patient outcome observational cohort 
Sponsor 
Zimmer Knee Creations 
Protocol Number 
KC.CR.I.AM.16.3 
Protocol Version 
2 
Number of Sites 
Approximately 30 
Number of 
Patients  
Approximately 1000 
Inclusion Criteria 
1. 
Surgeon considers patient appropriate for SCP® procedure. 
2. 
Patient has agreed to undergo the SCP® procedure or has 
already undergone the procedure. 
3. 
Subject is willing and able to sign a written consent form. 
4. 
The subject has the mental capacity and the willingness to 
contribute follow-up outcome data. 
5. 
Patient is willing and able to complete outcome forms in person 
or by phone, email or regular mail. 
Evaluation 
Parameters 
1. 
Detailed Patient Demographic Information 
2. 
Work/disability status 
3. 
Operative details 
4. 
Safety (i.e. adverse events) 
5. 
Visual Analog Scale (VAS)—Knee Pain  
6. 
International Knee Documentation Committee (IKDC) 
Subjective Knee Form 
7. 
VR-12 Health Survey  
8. 
Secondary Surgical Intervention 
 
2. 
Description of SCP® Procedure 
Subchondroplasty® (SCP®) is a procedure performed on subjects who have bone marrow 
lesion(s) (BML). BMLs are subchondral defects in the bone and the SCP procedure allows 
surgeons to place AccuFill® calcium phosphate (CaP) (bone void filler) at the defect site. SCP is 
performed on the subchondral bone of the knee utilizing an arthroscopic/percutaneous approach. 
Using standard arthroscopic surgery techniques, skin incisions are made for the insertion of 
arthroscopic instrumentation. Other arthroscopic procedures in the knee are performed per the 
surgeon’s operative plan for each subject. Using fluoroscopic guidance, the surgeon locates the 
BML and one or more AccuPort cannulas are drilled into the bone. Through the cannula, calcium 
phosphate bone void filler is injected into the bone marrow lesion until the edematous region is 
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filled. The calcium phosphate fills the edematous void (defect) and hardens within the BML. The 
calcium phosphate is resorbed over time and replaced with natural bone.  
 
3. 
Study Design 
This is a multi-center patient outcome observational cohort study intended to collect data on the 
short- and long-term safety and effectiveness of the SCP procedure. This observational cohort 
will become a repository of data reflecting patient experiences with the SCP procedure over 
time. Detailed patient demographic information (e.g., age, gender, location of defect, severity of 
symptoms, etc.) will be collected to determine the most suitable SCP patient population(s). The 
study duration is expected to be 10 years.  
 
3.1 
Study Population 
The SCP Observational Cohort study will enroll either patients undergoing SCP or 
patients who have already had the SCP procedure for the treatment of BMLs where bone 
void filler is placed at the site of the BML (defect).  
 
3.2 
Study Sites 
The study will be conducted at up to 30 sites. All will be trained on the SCP 
Observational Cohort study. 
 
3.3 
Sample Size 
As an observational cohort study there is no upper subject enrollment limit. Every patient 
undergoing the SCP procedure will be invited to participate in the study. The study goal 
is to collect data for approximately 1000 patients and evaluate demographics and 
outcomes data.  
 
4. 
Study Procedures 
 
4.1 
Subject Eligibility 
Enrollment will be based on the treating physician’s standard of care and the following 
criteria: 
1. Surgeon considers patient appropriate for SCP procedure. 
2. Patient has agreed to undergo the SCP procedure or has already undergone the 
procedure. 
3. Subject is willing and able to sign a written consent form. 
4. The subject has the mental capacity and the willingness to contribute follow-up 
outcome data. 
5. Patient is willing and able to complete outcome forms in person or by phone, 
email or regular mail. 
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4.2 
Subject Enrollment 
All patients considered for the SCP procedure by the investigator or who have had the 
SCP procedure will be invited to participate in the study.  Patients expressing an interest 
in participation will proceed with the informed consent process. No study activities will 
be performed prior to patient signature of the informed consent form. If the patient does 
not sign the informed consent, the patient will still undergo the SCP procedure, but they 
will not be included in the observational cohort study. Should a patient not undergo SCP, 
the patient will not be enrolled in the observational cohort study and will be reported as a 
screen fail. The enrollment status for each patient considered in the study will be 
appropriately documented on a screening log. 
 
4.3 
Subject Informed Consent 
Patients will provide written consent to be included in the SCP study. The informed 
consent form will conform to 21 CFR Part 50, Protection of Human Subjects.  Each 
patient must read, have an opportunity to have any questions addressed, and sign this 
form prior to being enrolled in the study.  
 
The investigator or appropriate study staff’s signature on the consent form will document 
that the informed consent process included the following items: 
• The subject was provided adequate time to read and review the consent form prior 
to signing it. 
• The subject was given an opportunity to ask any questions he/she had concerning 
the study. 
• The subject understands what their expectations are for participating in the study. 
• The information in the consent form was provided in a language the subject 
understands. 
• The subject signed the consent form prior to enrollment in the observational 
cohort study. 
• The subject received/will receive a copy of the signed and dated consent form. 
 
4.4 
Data Collection 
This section is applicable to individuals who have undergone screening, have signed an 
Informed Consent Document, and have otherwise been found eligible to participate in 
this study. This section details the pre-operative, operative, and post-operative 
management of Subjects.  
 
In order to minimize the burden to patient and physician, patients will be enrolled at the 
physician’s office, but will not be required to come back to the office for follow-up visits. 
The follow-up data to be collected as part of this study will be mailed or emailed to study 
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subjects by their study doctor at the selected time points (6 weeks, 3 months, 6 months, 1 
year, 2 years, 3 years, 4 years, and 5 years).  The patient will fill out the evaluation forms 
and then mail the forms back to their study doctor or complete them online.  These forms 
may also be completed by phone with study staff; however an approved phone script must 
be used.  Additionally, if the subject returns to the physician’s office during a follow-up time 
point, the evaluation forms may be completed in person. 
 
Zimmer Knee Creations will work with an electronic data capture (EDC) system 
developed to track all patient data for this observational cohort study. The EDC firm will 
complete the necessary diligence to ensure any platform selected meets the technical, 
reporting, data management, storage and security needs of the firm. Data collected on the 
CRFs will be included in the study database. 
 
4.4.1 
Preoperative Procedures 
Prior to surgery, the data in Table 1 must be collected for each enrolled Subject.   
 
Table 1: Preoperative Data Collection 
Form 1—Medical History 
Evaluation 
Details of Evaluation 
Enrollment Checklist  
Authorized medical personnel will verify subject 
eligibility. 
Patient Demographics 
Authorized medical personnel will collect basic 
demographics from the preoperative time period. 
Knee Related History 
Authorized medical personnel will collect 
previous/current treatments and previous/current 
medications (prescription drugs) for the affected 
knee, as well as previous surgical treatments. 
Concomitant Medical 
Conditions 
Authorized medical personnel will collect 
medical conditions from the preoperative time 
period. 
Current Medications 
Authorized medical personnel will collect current 
medications (prescription drugs) not related to the 
affected knee. 
 
 
 
 
 
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Form 2—Pre-Operative Clinical Evaluation 
Evaluation 
Details of Evaluation 
VAS—Knee Pain 
Each of the questionnaires should be completed 
by the Subject. It typically takes 5-10 minutes per 
questionnaire to complete. 
 
Length of Painful 
Symptoms 
Work/Disability Status 
IKDC 
VR-12 Health Survey 
 
4.4.2 
Operative Procedures 
The surgical process is to follow site standard of care.   
 
Data collected during the operative procedure of the Subject is listed in Table 2.  
 
Table 2: Operative Data Collection 
Form 3—Surgical Evaluation & Details 
Evaluation 
Details of Evaluation 
Imaging Evaluation  
Baseline MRI and Standing Alignment X-Ray 
dates. 
Standing Alignment 
Patient’s standing alignment. 
Bone Marrow Edema 
Location 
Surgeon must indicate locations of bone marrow 
edema on MRI. 
Surgical Procedure 
Details 
Description of Subject’s operative procedure 
including such items as findings and treatments, 
operative times and diagnoses. 
Adverse Event (if 
applicable) 
Description of adverse events occurring during 
the operative procedure, if applicable. 
 
4.4.3 
Postoperative Procedures 
Immediate post-operative management is at the discretion of the surgeon and support 
staff and should follow each Site’s standard of care.  
 
Data collection for this study will occur post-operatively at 6 weeks, 3 months, 6 
months, 1 year, 2 years, 3 years, 4 years and 5 years.  The post-operative visit data 
listed in Table 3 must be collected for each enrolled Subject either in person or by 
email, mail or telephone.   
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Table 3: Postoperative Data Collection 
Form 4—Post-Operative Evaluation 
Evaluation 
Details of Evaluation 
VAS—Knee Pain 
Each of the questionnaires should be completed 
by the Subject. It typically takes 5-10 minutes per 
questionnaire to complete. 
 
Medications 
Surgical/Non-Surgical 
Procedures 
Work/Disability Status 
IKDC 
VR-12 Health Survey 
Adverse Event (if 
applicable) 
Only AEs which are possibly or definitely 
related to the device or procedure will be 
reported to the sponsor.   
 
Serious AEs must be reported as soon as 
possible and within 24 hours after the 
investigator first learns of the event.  The 
Sponsor is subsequently responsible for reporting 
as required.  
 
See Adverse Event Reporting in Section 5.  
End of Study/ 
Withdrawal 
At any time during the study a Subject may 
withdraw.  Subject withdrawal must be 
documented and provided to the Sponsor. 
 
4.5 
Data Analysis 
Please note that detailed patient demographic information (age, gender, location of 
defect, severity of symptoms, etc.) will be collected and analyzed to identify suitable 
candidates for SCP and to perform covariate analyses on the post-operative clinical 
outcomes for the study population. 
 
5. 
Adverse Event Reporting 
 
5.1 
Adverse Events 
An adverse event (AE) is defined as an untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs (or change or worsening of a pre-existing 
medical condition) in a patient, which may or may not have an association with the 
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device. In addition an adverse device effect is defined as ‘any untoward and unintended 
response to a medical device’. 
 
For this study, only AEs which are possibly or definitely related to the device or 
procedure will be reported to the sponsor.  The determination whether the AE is 
related to the device or procedure will be based upon whether a causal relationship 
between the device or procedure and the AE is at least a reasonable possibility, i.e. the 
relationship cannot be ruled out. A causal relationship cannot be ruled out if, in the 
medical judgment of the investigator, the effect follows a reasonable temporal association 
with the use of the device and/or is confirmed by the improvement of the effect upon 
discontinuation of the clinical use of the device, and/or the effect is not reasonably 
explained by the Subject’s clinical state.  
 
Relationship to study device or procedure should be rated as follows:   
1. None (definitely not related): there is no relationship between study device or 
procedure and the event.  
2. Possible (remote possibility, possibly, or probably related): the relationship 
between study device or procedure could exist if there is no contradicting 
evidence that can reasonably explain the Subject’s condition.  
3. Definite (definitely related): the relationship between study device or procedure 
and event does exist and is confirmed upon further investigation by the 
investigator. 
 
Pre-existing medical conditions or symptoms reported prior to device implantation 
are not to be recorded as AEs. In the event there is an exacerbation of the pre-existing 
medical condition or symptoms (due to the device or study related procedure), then an 
AE must be reported. 
  
AEs are reported beginning from time of surgery until Subject participation has ended 
(study completed or Subject withdrawn).  AEs must be followed to resolution or until the 
study completion or Subject withdrawal.  
 
Subjects should be encouraged to report AEs spontaneously and may volunteer AE 
information at any time. At each evaluation, the investigator will determine whether an 
AE has occurred. If it is determined that an AE has occurred, the investigator should 
obtain all the information required to complete the appropriate AE form(s). If an event 
occurs at an outside institution, the investigator should attempt to obtain, if possible, 
required AE information to report to the Sponsor. 
 
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The investigator will record the nature, severity, treatment and outcome of the AE, and 
will determine their association to the device or the study procedure. 
The following categories of AE severity are to be used:  
1. Mild: awareness of a sign, symptom or event that is easily tolerated and transient 
in nature with minimal or no impairment to normal activity. 
2. Moderate: moderate symptoms that are poorly tolerated, sustained, interfere with 
normal activity and require medical attention.  
3. Severe: symptom(s) require intervention, and the activities of daily living are 
significantly altered. 
 
5.2 
Serious Adverse Events 
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that: 
1. Results in death  
2. Is a life-threatening illness or injury 
3. Requires inpatient hospitalization or prolongation of existing hospitalization  
4. Results in persistent or significant disability/incapacity, or  
5. Is a congenital anomaly/birth defect 
6. Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or function.     
7. Other serious (Important Medical Events).  Report when the event does not fit the 
other outcomes, but the event may jeopardize the patient and may require medical 
or surgical intervention (treatment) to prevent one of the other outcomes.  
 
For the purpose of this protocol, any surgical intervention is considered a serious 
adverse event.  In case of death, all possible information available, such as autopsy or 
other post-mortem findings should be provided. 
 
SAEs must be reported to the Sponsor as soon as possible and within 24 hours after 
the investigator first learns of the event.  SAEs are reported to the respective 
Institutional Review Board (IRB) or Ethics Committee (EC), as per their respective 
requirements by the site. 
 
6. 
Missed Follow-up Completion of Questionnaires 
If a subject fails to complete the post-operative questionnaires at a follow-up time point, the site 
should continue to attempt follow-up of the subject through the five year study end point. The 
subject should only be considered Lost to Follow-Up and exited from the study under the 
conditions described in section 7.2.  There should be at least three documented attempts to 
contact the subject to obtain follow-up data with any combination of an email reminder via 
OBERD, a phone call or an IRB approved subject follow-up letter. 
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7. 
Discontinuation of Subject Participation  
 
7.1 
End of Study/Withdrawal 
Study participation may be discontinued through surgical revision (Partial, Total Knee 
Arthroplasty or total removal of AccuFill), withdrawal of consent, investigator decision 
or death.  All consented Subjects who are withdrawn/discontinued from the study should 
have an end of study form completed to explain why they are no longer participating in 
the study.  This form should be sent to the Sponsor upon completion and placed in the 
subject’s binder. 
 
7.2 
Lost to Follow-Up 
If the subject does not complete the required questionnaires through the five year time 
point and the Investigator or Study Coordinator has attempted to contact that subject at 
least three times via email reminder through OBERD, a phone call or an IRB approved 
subject follow-up letter and receives no response, the subject may be deemed to be lost to 
follow-up. The research staff should have documentation of the attempts to contact the 
subject. The final attempt to contact the subject will be performed by certified mail and 
the receipt will be placed in the subject’s file. An end of study form must be completed, 
sent to the Sponsor and also placed in the subject’s file.  
 
Should a subject who previously chose to withdraw their consent wish to re-enter the 
study, a new signed Informed Consent Document will be required.  The site may resume 
follow-up visits as long as they are within the designated visit window.   
 
8. 
Protocol Adherence 
The Investigator(s) agrees to conduct the study in accordance with this protocol.  For the purpose 
of this study, only violations that affect the subject’s rights, safety, or welfare, or the integrity of 
the data will be recorded.  A log of the violations will be kept within the site’s regulatory binder 
and sent to the Sponsor when any violations have occurred. 
 
A protocol violation can be described as accidental or unintentional change to, or non-
compliance with the IRB approved protocol without prior Sponsor and IRB approval. Violations 
generally increase risk and/or decrease benefit, affects the subject's rights, safety, or welfare, or 
the integrity of the data.  Examples include failure to obtain valid informed consent (e.g., 
obtained informed consent on an unapproved consent form), loss of laptop/computer that 
contained identifiable and private information about subjects or not following 
inclusion/exclusion criteria. 
 
Protocol deviations will not be collected for this study nor added to the protocol violation log.  A 
protocol deviation is an accidental or unintentional change to or non-compliance with the 
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research protocol that does not increase risk or decrease benefit or does not have a significant 
effect on the subject's rights, safety or welfare, and/or on the integrity of the data.  A deviation 
may be due to the research subject’s non-adherence or an unintentional change to or non-
compliance with the research protocol on the part of a researcher.   
 
9. 
Ethical Considerations 
 
9.1 
IRB Approval 
IRB approval will be obtained prior to patient enrollment at each site. The revocable 
informed consent form will conform to 21 CFR Part 56, Institutional Review Boards.   
 
9.2 
Protection of Patient Confidentiality  
All HIPAA requirements for subject confidentiality will be maintained.  
  
Only approved study personnel shall have access to the patient records. None of the 
specific patient data will be disclosed to persons or organizations not involved in the 
research.  Reports generated will not identify individual patients in any way.   
 
In addition to protection of patient privacy rights, Zimmer Knee Creations will use due 
diligence to restrict access to this study platform and patient outcomes. Zimmer Knee 
Creations will maintain exclusive responsibility for study administration and oversight.  
 
Zimmer Knee Creations will complete the development of this observational cohort 
program; provide training and continuing education on proper methods for data 
collection, entry and reporting; and oversee compliance with patient privacy rights 
including HIPAA.  
 
10. 
Subject Stipends or Payments 
Subjects will receive stipends based on each site’s respective budget and informed consent form. 
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