The JewelACL Post Market Clinical Follow Up Study - Multicentre Study of at Least 5 Years Follow up, Looking at Clinical Outcomes in Patients Treated With the JewelACL for Anterior Cruciate Ligament (ACL) Reconstruction
Conditions: Anterior Cruciate Ligament Injuries
Sponsor: Xiros Ltd



 
 
 
 
 
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PRINCIPAL INVESTIAGTOR SIGNATURE PAGE 
 
 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation 
 
 
Principal Investigator 
 
 
Printed Name: 
 
Signature: 
 
Date: 
 

 
 
 
 
 
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TABLE OF CONTENTS 
 
1. 
AMENDMENT HISTORY ......................................................................................................................... 6 
2. 
SYNOPSIS .................................................................................................................................................... 7 
3. 
INTRODUCTION ........................................................................................................................................ 8 
4. 
DEVICE DESCRIPTION ........................................................................................................................... 9 
5. 
BACKGROUND AND JUSTIFICATION FOR STUDY ....................................................................... 13 
6. 
DEVICES USED IN THE STUDY ........................................................................................................... 15 
7. 
OBJECTIVES ............................................................................................................................................ 16 
8. 
STUDY DESIGN ........................................................................................................................................ 17 
9. 
STUDY PROCEDURES ............................................................................................................................ 18 
10. 
INVESTIGATOR RESPONSIBILITIES ............................................................................................ 25 
11. 
SAFETY REPORTING ........................................................................................................................ 26 
DEFINITIONS ..................................................................................................................................................... 26 
REPORTING OF AE............................................................................................................................................. 28 
REPORTING PROCEDURES FOR ALL SAES/ SADES/ UADES ............................................................................ 28 
12. 
STATISTICS .......................................................................................................................................... 29 
DESCRIPTION OF STATISTICAL METHODS .......................................................................................................... 29 
THE NUMBER OF PARTICIPANTS ........................................................................................................................ 29 
THE LEVEL OF STATISTICAL SIGNIFICANCE ...................................................................................................... 29 
CRITERIA FOR THE TERMINATION OF THE STUDY .............................................................................................. 29 
PROCEDURE FOR ACCOUNTING FOR MISSING, UNUSED, AND SPURIOUS DATA ................................................. 29 
PROCEDURES FOR REPORTING ANY DEVIATION(S) FROM THE ORIGINAL STATISTICAL PLAN ........................... 30 
INCLUSION IN ANALYSIS ................................................................................................................................... 30 
13. 
RISK AND BENEFITS ......................................................................................................................... 31 
14. 
CLINICAL DATA HANDLING .......................................................................................................... 33 
15. 
MONITORING ...................................................................................................................................... 35 
16. 
ETHICS .................................................................................................................................................. 36 
17. 
COMPLIANCE...................................................................................................................................... 37 
18. 
SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL INVESTIGATION .. 38 

 
 
 
 
 
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19. 
PUBLICATION ..................................................................................................................................... 39 
20. 
REPORTING RESULTS ON CLINICALTRIALS.GOV ................................................................. 40 
21. 
REFERENCES ...................................................................................................................................... 41 
APPENDIX 1 ....................................................................................................................................................... 42 
 
 
 

 
 
 
 
 
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1. 
AMENDMENT HISTORY 
 
. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details 
of 
Changes 
made 
 
 
 
 
 

 
 
 
 
 
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2. 
SYNOPSIS 
 
 
 
 
 
Study Title 
The JewelACL Post Market Clinical Follow Up Study – Multicentre study of at 
least 5 years follow up, looking at clinical outcomes in patients treated with the 
JewelACL for ACL reconstruction 
Internal ref. no. 
CRE 027 
Type of study 
Post Market Clinical Follow Up 
Study Design 
Retrospective data collection with at least 5 years follow up and telephone call 
to collect patient reported outcomes. 
Study Participants 
Patients treated with the JewelACL for ACL Reconstruction 
Planned Sample Size 
120 subjects 
Follow-up duration 
5 Years Follow Up 
Planned Study Period 
9 Months 
Primary Objective 
The primary objective is to assess, at least 5 year re-rupture rate from subjects 
who were implanted with the JewelACL device for ACL reconstruction.   
Secondary Objectives 
To report on all recorded adverse events  
To assess whether fixation type and autograft use have an effect on failure 
rates. 
To review patient reported outcome scores at a minimum of 5 year follow up 
and assess change from baseline, if baseline scores are available. 
Primary Endpoint 
Reconstruction Failure 
Secondary Endpoints 
IKDC score at 5 years minimum (compared to baseline, if available) 
Lysholm score at 5 years minimum (compared to baseline, if available) 
Tegner Activity score at 5 years minimum (compared to baseline, if available) 
Assessment of adverse events at 5 years minimum 
Device Name  
JewelACL  
Manufacturer Name  
Xiros Ltd 
Principal intended use  
 The JewelACL is intended to be used for reconstruction of the anterior 
cruciate ligament. 

 
 
 
 
 
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3. 
INTRODUCTION  
This document is a clinical investigation plan (CIP) for the JewelACL Post Market Clinical Follow-Up 
(PMCF) study.  The objective of the study is to assess re-rupture rates and patient outcomes from 
subjects with at least 5 year follow up, treated with the JewelACL device for ACL reconstruction. The 
impact of fixation type and autograft augmentation will also be assessed.  All adverse events related to 
the JewelACL device will be recorded.  This study is Sponsored by Xiros. 
 
This PMCF study will be conducted in accordance with this CIP.  All parties involved in the conduct of 
the study will be qualified by education, training, or experience to perform their tasks and this training 
will be documented appropriately. 

 
 
 
 
 
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4. 
DEVICE DESCRIPTION 
The JewelACL is a polyester scaffold for anterior cruciate ligament (ACL) reconstruction. It is  
matched in tensile strength to the semitendinosus hamstring tendon, which is typically 1200 N, and  
can be used with or without an additional tissue graft in either partial or total tissue sparing ACL  
reconstruction procedures (LAB 139 8.00). 
 
 
The JewelACL is made from polyethylene terephthalate (polyester). The polyester has been subjected  
to a proprietary gas plasma process that modifies its surface properties, making it hydrophilic, without  
significantly altering the physical characteristics of the bulk material (LAB 139  
8.00). 
 
The polyester yarn is woven in a mock-leno pattern; an open weave structure to permit the ingrowth of 
tissue, which can remodel to form a ‘neoligament’.  It is tubular in structure to allow placing a 
hamstring tendon graft inside it.  
 
The JewelACL is in the form of a tube 710 mm long with an internal diameter of 7 mm.  It has a mean  
tensile strength of 1245 N (TR 105).  When doubled, as in use, this will have a strength of up to 1977  
N (TR 105).  
 
The JewelACL is packed in a double blister in a cardboard box, supplied with an IFU and patient  
labels. 
 

 
 
 
 
 
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The device does not incorporate medicinal substances, animal/human tissues or blood products. The  
device is supplied sterile (by gamma irradiation; 25-50 kGy) and remains sterile unless the packaging  
is damaged or opened. 
 
4.1 Intended Use 
The JewelACL is intended to be used for reconstruction of the anterior cruciate ligament     
 
(ACL). 
 
4.2 Indications 
The JewelACL is indicated for all patients requiring ACL reconstruction that are not     
 
excluded by the contraindications listed below. 
 
   
      Contraindications 
• 
Known hypersensitivity to implant materials. If the patient is suspected of having any 
foreign body sensitivity, appropriate tests should be made prior to implantation. 
• 
Infections, or any structural or pathological condition of the bone or soft tissue that 
would be expected to impair healing or secure fixation. 
• 
Patients unable or unwilling to restrict activities to prescribed levels or follow a 
rehabilitation programme during the healing period. 
• 
The JewelACL may not be suitable for skeletally immature patients as it will not 
lengthen instep with the patients growth into adulthood, and so must not bridge, 
disturb, or disrupt the growth plate. 
• 
Patients for whom it is not possible to bend the knee to at least 90º as it will not be 
possible to reach the correct position for drilling the bone tunnels. 

 
 
 
 
 
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4.3 Risk and Benefits of the JewelACL Device 
 
4.3.1  JewelACL Risks 
The JewelACL is a CE marked device. The risks of device use are low, and in 
line with alternative devices and techniques used in current practice. Potential 
device risks include: 
• 
Infections, both deep and superficial. 
• 
Patient body sensitivity and adverse reaction to device materials. 
• 
Synovitis in the knee 
• 
Laxity or reduced Range of Motion are potential adverse consequences of 
misplacing the ligament. 
• 
Laxity may also result from inadequate fixation of the ligament to bone. 
 
4.3.2  JewelACL Benefits 
The JewelACL is intended to reconstruct the ACL and therefore result in: 
• 
Significant improvement in the performance of the injured knee over that 
before surgery 
• 
Rapid return to work and sport (in less than six months) 
• 
Can be used to provide additional strength to autograft tissue 
If used without any autograft: 
• 
No pain or weakness from donor site 

 
 
 
 
 
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• 
Useable for revision or primary surgery where there is lack of availability 
of useable graft tissue. 
• 
Quicker operation than when graft tissue is harvested. 

 
 
 
 
 
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5. 
BACKGROUND AND JUSTIFICATION FOR STUDY 
5.1 Clinical Background 
The ACL is the most commonly injured ligament in the knee (Gans et al., 2018).  It serves to 
restrain the anterior displacement of the tibia with respect to the femur, as well as providing 
rotational stability to the knee and some protection from varus and valgus stress.  
5.2 Introduction to ACL Treatment 
There are many treatment pathways for ACL injury.  The patient may have conservative treatment 
with rehabilitation and may fare well, even returning to sport.  This is the usual approach for older 
patients.  Young and active sports people are more likely to need surgery, which must be followed 
by a strict rehabilitation programme (van Melick et al (2016)). Surgically the options are: 
• 
Repair in which the native tissue is sutured, but no graft is added.  Examples include 
Internal Brace Ligament Augmentation and Dynamic Intraligamentary Stabilisation. 
• 
Reconstruction surgery in which the ruptured ACL is replaced with a biological tendon 
graft fixed into bone tunnels in the femur and tibia.  There are several sources of tendon 
graft: an autograft from the patient or an allograft from a donor.  The most common 
autografts are the medial third of the patella tendon, a hamstring graft or a quadriceps 
tendon. 
• 
Reconstruction using a synthetic ligament, such as the JewelACL or LARS ligaments, 
both of which are is made of polyester.  
5.3 Knee Outcome scoring methods 
There are several methods of assessing the outcomes of knee surgery, of which three of the 
most used are briefly described below: 

 
 
 
 
 
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IKDC (International Knee Documentation Committee) – a score based on a questionnaire 
with three components: symptoms, sports activity and knee function.  The score may range 
between 0 (very poor outcome) and 100 (very good outcome).    
Lysholm – a scoring system especially for ACL surgery consisting of eight items which are 
summed to give a total: pain (25 points), instability (25 points), locking (15 points), swelling 
(10 points), limp (5 points), stair climbing (10 points), squatting (5 points) and need for 
support (5 points).  The best outcome would be 100 points.  
Tegner – a scale to identify the graded level of activity of a patient, usually used in 
conjunction with the Lysholm scale.  The scale ranges from 0, very low level of activity, to 10 
extremely active, such as an international elite sportsman or woman.  A score of greater than 6 
is only achievable with participation in sport. 
5.4 Justification of study 
The clinical evaluation for the JewelACL (CER 007 v2) identified that there was a lack of 
long term follow up data for the device, with most studies reporting on two years outcomes.  
Therefore, this study aims to assess the long-term performance of the JewelACL when used 
for ACL reconstruction (in total and partial tissue sparing procedures), by means of clinical 
outcomes.  It will also review the adverse events observed in patients implanted with the 
JewelACL, and whether fixation type or use with an autograft affects the outcomes. This 
study will be collating data from sites which have previously used the JewelACL and have 
patients with at least 5 years follow up data.  Data will be collected on patients who have been 
implanted with the JewelACL to reconstruct the ACL between 01 October 2010 to 31 
December 2014   
 
 
 

 
 
 
 
 
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6. 
DEVICES USED IN THE STUDY 
 
6.1 Name of Device 
      JewelACL  
 
6.2 Manufacturer Name 
      Neoligaments™ A division of Xiros™  
      Springfield House,  
      White House Lane, 
       Leeds LS19 7UE  
       UK 
 
6.3 Principles of Operation of the device 
The reconstruction of a ruptured ACL can be performed by passing a replacement ligament 
graft/scaffold such as the JewelACL, along the same path as the native ligament between the 
femur and the tibia.   The JewelACL is attached to the bones by passing it through bone 
tunnels in the distal femur and proximal tibia and securing it to the bone cortices.  Placement 
of the tunnels is critical and should observe isometry of the implant, which means retaining its 
length during flexion and extension, as the device is stiff and permits only small extensions.   
The JewelACL is held in the femoral tunnel by doubling it over a suspension device.  Both 
ends of the device are secured at the tibia with a soft thread interference screw in the bone 
tunnel or a staple in the bone cortex.   
The JewelACL is designed as a scaffold for tissue ingrowth, a process which may be assisted 
by the incorporation of a tendon graft into the tubular structure of the device.   
6.4 Intended Users 
The JewelACL is for use by orthopaedic surgeons who are thoroughly familiar with the 
recommended surgical procedure. 

 
 
 
 
 
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7. 
OBJECTIVES 
7.1 Primary Objective 
The primary objective of the study is to assess at least 5-year re-rupture rate from subjects 
who were implanted with the JewelACL device for ACL reconstruction.  
 
7.2 Secondary Objectives 
Secondary objectives of the study are: 
• 
to report on all recorded adverse events; 
• 
to assess whether fixation type and autograft use have an effect on failure rates; 
• 
To assess patient reported outcomes at 5 years minimum (PROMS: IKDC; Lysholm; 
Tegner) 
• 
To assess changes in patient reported outcome scores from baseline, if available 
(PROMS: IKDC; Lysholm; Tegner). 
 
7.3 Endpoints 
Primary 
• 
Reconstruction failure at final follow-up 
Secondary 
Clinical 
• 
Assessment of adverse events 
Patient Outcomes 
• 
IKDC Subjective Knee Evaluation 
• 
Lysholm knee scoring scale 
• 
Tegner Activity 

 
 
 
 
 
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8. 
STUDY DESIGN 
This is multicentre clinical study, collating real-world clinical outcomes for the JewelACL device 
used to reconstruct the ACL. Medical records of subjects who were treated using the JewelACL 
device for ACL reconstruction, between 01 October 2010 to 31st December 2014 will be reviewed 
against the inclusion and exclusion criteria.  Subjects that meet all of the inclusion criteria and none of 
the exclusion criteria will be enrolled into the study. Data will be collected as per the endpoints and 
entered in the Electronic Case Report Form used for this study. 
A telephone follow-up will be conducted for each subject enrolled into the study; this follow up call 
will collect the following: 
• 
Reconstruction Failure (any ACL failure and if so, what, when and how?) 
• 
Details of any complications or revision of the reconstruction (including date of 
procedure,  
• 
IKDC Subjective Evaluation, Lysholm knee scoring scale and Tegner Activity 
 
8.1 Study Population 
Consecutive patients who have had the JewelACL device used to reconstruct the ACL, 
between the period of 01 October 2010 to 31 December 2014. 
 
8.1.1 Inclusion Criteria 
 
Eligible patients who meet all of the following: 
1. Age >18 years  
2. Patients previously implanted with the JewelACL for ACL reconstruction 
(Primary JewelACL cases only, no revision cases) 
 
 
8.1.2 Exclusion Criteria 
          Patients will be excluded if they meet any of the following 
1. Age <18 years 
2. Any implantations for non-indicated conditions, as stated in the IFU 
3. Revision cases  

 
 
 
 
 
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9. 
STUDY PROCEDURES  
Approval from the Sponsor and Ethics Committee must be received prior to initiating study 
procedures. 
The following sections provide a detailed description of procedures required by this CIP. 
   
9.1 Patient Recruitment 
Only patients treated with the JewelACL for ACL reconstruction between 01 October 2010 to 
31 December 2014 will be reviewed for the purpose of this study.  Data will only be collected 
from the medical records of patients who meet all of the inclusion criteria and none of the 
exclusion criteria. 
   
9.2 Informed Consent Process 
The study design is retrospective data collection with a telephone call follow up at 5 years 
post-surgery.  Verbal consent will be required for all eligible patients who agree to consent to 
the telephone follow-up, and this process is required to be recorded within the medical notes. 
The Principal Investigator or his/her authorised designee will conduct the verbal informed 
consent.  This process will include a verbal discussion of all aspects of the study that are 
relevant to the subject’s decision to participate, such as the purpose of the study and 
anticipated benefits.  During the discussion, the Principal Investigator or his/her authorized 
designee will avoid any improper influence on the subject and will respect the subject’s legal 
rights.  If the subject agrees to give their verbal consent, then the Principal Investigator or 
his/her authorised designee must document this process in the medical or research notes and 
the process will be recorded within the Electronic Case Report Form. 
 
Failure to obtain verbal informed consent from a subject to participate in the telephone follow 
up will mean that the follow up telephone call must not take place.  Retrospective data will 
still be collected as no patient identifying data will be recorded. 

 
 
 
 
 
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The justification for verbal consent within this study is that it prevents the subject having to 
return to the site to sign an informed consent form in person.  This would put additional 
burden on  the patient, when the only data collected during the telephone follow up will be the 
collection of  patient outcomes using questionnaires e.g. IKDC Subjective Knee Evaluation, 
Lysholm knee scoring scale and Tegner Activity and asking about any complications 
experienced, all of which can be conducted over the phone. 
 
9.3 Point of Enrolment 
All subjects who meet all inclusion criteria and do not meet any of the exclusion criteria will 
be considered enrolled into the study. 
The Principal Investigator or delegated study personnel will record enrolment information in 
the medical records and complete and submit all applicable CRFs in a timely manner. 
 9.4 Scheduled Procedures 
The Principal Investigator is responsible for ensuring all clinical data is collected as required 
per CIP scheduled procedures.  The data collection elements required for each study visit are 
summarised in Table 1. 

 
 
 
 
 
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TABLE 1: Summary of study procedures 
Study activities (Data 
Collection) 
Baseline 
Procedure 
Surgery to 
6 months 
(if 
available) 
6 months 
to 24 
months (if 
available) 
Telephone 
call follow up 
(at least 5 
years post-
surgery) 
 
Verbal Consent 
 
 
 
 
 
 
 
X 
 
Medical History 
 
 
X 
 
 
 
 
 
 
Age and gender at time of 
JewelACL implantation 
 
 
 
 
X 
 
 
 
 
Participation in sports 
 
 
X* 
 
 
X* 
 
X* 
 
X 
 
Date of surgery/follow-up 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
ACL failure injury mode 
 
 
X 
 
 
 
 
 
 
 
 
 
Reconstruction Failure 
 
 
 
 
X 
X 
X 
 
Hybrid (with autograft) or non-
hybrid (JewelACL only) 
 
 
 
X 
 
 
 
 
Fixation type (tibial and 
femoral) 
 
 
 
X 
 
 
 
 
Any other procedures recorded 
during ACL procedure 
 
 
 
X 
 
 
 

 
 
 
 
 
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Study activities (Data 
Collection) 
Baseline 
Procedure 
Surgery to 
6 months 
(if 
available) 
6 months 
to 24 
months (if 
available) 
Telephone 
call follow up 
(at least 5 
years post-
surgery) 
 
Details of any complications or 
revision of the reconstruction 
 
 
 
X 
 
X 
 
X 
 
X 
 
IKDC Subjective Knee Evaluation 
 
 
*X 
 
 
*X 
 
*X 
 
X 
 
Lysholm and Tegner 
 
 
*X 
 
 
*X 
 
*X 
 
X 
 
* If available in medical records 
 
 
 
9.4.1 Baseline Visit (Data collection from medical notes) 
 
For patients treated with the JewelACL device to reconstruct the ACL, during the 
 
period from the 01 October 2010 to 31st December 2014, a baseline data collection 
 
visit will occur retrospectively.  Data available in the patient’s medical records will be 
 
used to fulfil baseline requirements. 
 
The Baseline visit consists of the following activities: 
• 
Medical History including history of the knee(s) e.g. previous surgeries. 
• 
Participation in sports (if available). 
• 
Patient reported outcome score e.g. IKDC Subjective Knee Evaluation, 
Lysholm knee scoring scale, Tegner Activity (if available). 
 
 
9.4.2 Procedure Visit (Data collection from medical notes) 
 
Procedure data will be collected retrospectively if available in the patient’s medical 
 
records, to be used to fulfil the procedure requirements. 
 
The Procedure visit consists of the following activities: 
• 
Date of surgery. 

 
 
 
 
 
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• 
Age and gender at time of JewelACL implantation. 
• 
ACL failure injury mode (whether failure occurred in a sport’s accident, or 
any other documented accident)/date.  
• 
Information on the procedure: 
▪ 
Hybrid (with autograft) or non-hybrid (JewelACL only). 
▪ 
Fixation type (tibial and femoral). 
• 
Any other procedures during surgery (e.g. multi-ligament repair, meniscus 
repair). 
 
 
9.4.3 Medical record follow up, from surgery to 6 months (Data collection from   
 
 
 medical notes, if available) 
 
Follow up data from surgery to 6 months will be collected retrospectively to be used 
 
to fulfil the follow up requirements: 
• 
Date of follow up. 
• 
Reconstruction Failure (any graft failure and if so, what, when and how?). 
• 
Details of any complications or revision of the reconstruction (including date, 
and cause of failure if known). 
• 
Patient reported outcome score e.g. IKDC Subjective Knee Evaluation, 
Lysholm knee scoring scale, Tegner Activity. 
 
 
9.4.4 Medical record follow up, 6 months to 24 months (Data collection only, if 
 
 
available) 
 
Follow up data from 6 months to 24 months will be collected retrospectively to be 
 
used to fulfil the follow up requirements: 
• 
Date of follow up. 
• 
Reconstruction Failure (any graft failure and if so, what, when and how?). 

 
 
 
 
 
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• 
Details of any complications or revision of the reconstruction (including date, 
indication and cause of failure if known). 
• 
Patient reported outcome score e.g. IKDC Subjective Knee Evaluation, 
Lysholm knee scoring scale, Tegner Activity. 
 
 
9.4.5 Telephone call follow up (at least 5 years post-surgery) 
 
A patient telephone follow-up will be conducted only on subjects who have given 
 
verbal informed consent. Please refer to Informed Consent procedure Section 9.2   
 
The following will be collected during the telephone follow up 
• 
Verbal consent (ensure this process is documented). 
• 
Date of Follow Up. 
• 
Participation in sports. 
• 
Reconstruction Failure (any graft failure and if so, what, when and how?). 
• 
Details of any complications or revision of the reconstruction. 
• 
Completion of IKDC Subjective Knee Evaluation. 
• 
Completion of Lysholm and Tegner scores. 
The IKDC, Lysholm and Tegner scoring at final follow up, must be completed by hand and 
filed within the site file.  Paper copies will be provided to each site participating in the study.  
Lysholm and Tegner final follow up scores will be entered directly into the Electronic Case 
Report Form.  IKDC at final follow up will be collected and calculated by the sponsor and 
scores will be included in the final clinical report. 
   
9.6 Electronic Case Report Form 
All retrospective data will be entered directly from the subject’s medical notes into the 
Electronic Case Report Form.  Final telephone follow up data, Lysholm and Tegner scores 

 
 
 
 
 
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will be entered directly into the Electronic Data Capture System. IKDC scores will be 
calculated by the sponsor, therefore entry of the score will not be required at final follow up 
   
9.7 Subject Study Completion 
Subject participation in the clinical investigation will conclude upon completion of the data 
collection point from 6 months to 24 months post-surgery for ACL reconstruction using the 
JewelACL device. 
For patients who give verbal informed consent to take part in the telephone follow up, the 
clinical investigation will conclude upon completion of the follow up phone call. 
 
 
 
 
 

 
 
 
 
 
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10. 
INVESTIGATOR RESPONSIBILITIES 
The role of the Investigator at each site is to implement and manage the day-to-day conduct of the 
clinical investigation as well as ensure data integrity and the rights, safety and well-being of the 
subjects involved in the clinical investigation.  They are required to adhere to this CIP. 
The Principal Investigator shall be qualified by education, training and experience to assume 
responsibility for the proper conduct of the clinical investigation.  Evidence of this will be provided to 
the sponsor through up-to-date CVs.   
Principal Investigators must be experienced and have implanted the JewelACL device for ACL 
reconstruction.  They must disclose any potential conflicts of interest, including financial, that 
interfere with the conduct of the clinical investigation or interpretation of results, and be 
knowledgeable with the method of obtaining informed consent. 
 
 
 
 

 
 
 
 
 
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11. 
SAFETY REPORTING 
Definitions 
Device deficiency: 
Any alleged inadequacy related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a device after it is released for distribution. 
Note: This definition includes malfunctions, use errors, and inadequate labelling. 
Malfunction: 
A malfunction is a failure of the device to meet its performance specifications or otherwise perform as 
intended. Performance specifications include all claims made in the labelling for the device. A 
malfunction should be considered reportable if a serious adverse event has occurred or could occur as 
a result of a recurrence of the malfunction. 
Adverse Event (AE): 
An AE or adverse event is: 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, 
including an abnormal laboratory finding, in subjects, users or other persons, in the context of a 
clinical investigation, whether or not related to the investigational device. 
Adverse Device Effect (ADE): 
All untoward and unintended responses to the medical device.  
The phrase "responses to a medical device" means that a causal relationship between the device under 
investigation and an AE is at least a reasonable possibility, i.e., the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or the sponsor as having a 
reasonable suspected causal relationship to the device qualifies as a device effect.   

 
 
 
 
 
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This also includes any event resulting from insufficiencies or inadequacies in the instruction for use or 
deployment of the device and includes any event that is a result of a user error.  
Serious Adverse Event (SAE):  
'Serious adverse event' means any adverse event that led to any of the following: 
• 
death, 
• 
serious deterioration in the health of the subject, that resulted in any of the following: 
o life-threatening illness or injury, 
o permanent impairment of a body structure or a body function, 
o hospitalisation or prolongation of patient hospitalisation, 
o medical or surgical intervention to prevent life-threatening illness or injury or  
permanent impairment to a body structure or a body function, 
o chronic disease, 
• 
foetal distress, foetal death or a congenital physical or mental impairment or birth defect 
Serious Adverse Device Effects (SADE):  
A serious adverse device effect (SADE) is any untoward medical occurrence seen in a patient that can 
be attributed wholly or partly to the device which resulted in any of the characteristics or led to a 
characteristics of a Serious adverse event.  
SADE is also any event that may have led to these consequences if suitable action had not been taken 
or intervention had not been made or if circumstances has been less opportune.  
All cases judged by either the reporting medically qualified professional or the sponsor.  
Unanticipated Adverse Device Effect (UADE):  
Any serious adverse device 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 

 
 
 
 
 
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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 related to the rights, safety or welfare of the subject. 
Reporting of AE 
All AE’s occurring during the study observed by the investigator or reported by the participant, 
whether or not attributed to the device under investigation will be recorded on the CRF as specified in 
the protocol.  All ADE’s will be recorded in the CRF.  
The following information will be recorded: description, date of onset and end date, severity, 
assessment of relatedness to device, other suspect drug or device and action taken.  Follow-up 
information should be provided as necessary.  
The relationship of AEs to the device will be assessed by a medically qualified investigator or the 
sponsor/manufacturer and will be followed up until resolution or the event is considered stable.  
All ADE that result in a participant’s withdrawal from the study or are present at the end of the study, 
should be followed up until a satisfactory resolution occurs. 
Where relevant, any pregnancy occurring during the clinical study and the outcome of the pregnancy, 
should be recorded and followed up for congenital abnormality or birth defect. 
Reporting Procedures for All SAEs/ SADEs/ UADEs 
Considering the data collected in this study is on a CE marked product being used within its intended 
use, and the retrospective nature of the study, all  SAE/SADE/UADEs reported as part of the study 
will be managed in accordance with Xiros Standard Procedure for Product Events Reports and 
Vigilance.  
 

 
 
 
 
 
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12. 
STATISTICS 
Description of Statistical Methods 
The primary analysis will summarise the re-rupture rate of patients. The number and percentage of 
patients who have experienced a re-rupture will be reported. Additionally, a corresponding confidence 
interval will be reported for the percentage of patients with a re-rupture. The analysis will be performed 
for all patients combined, and also separately for the subgroups of patients receiving JewelACL alone, 
and those receiving JewelACL in combination with autograft.  
A single analysis will be performed at the end of the study, no interim analyses will be performed.  
The Number of Participants 
The sample size was calculated to ensure an accurate estimate of the re-rupture rate in patients 
receiving JewelACL. Based on previous data and clinical experience, the re-rupture rate is expected to 
be 10% (or less). The sample size was calculated so that the uncertainty in the calculated compared to 
the ‘true’ population percentage is not more than ±6%. Using a 95% level of confidence, it is calculated 
that 96 subjects are required for the study. In order to allow for a 20% drop-out, 120 subjects will be 
recruited into the study.  
The Level of Statistical Significance 
As there are no planned hypothesis tests, the level of significance is not relevant to this study. All 
confidence intervals will be calculated using a 95% confidence level.  
Criteria for the Termination of the Study  
Not Applicable. The study will not be terminated based on any data collected.  
Procedure for Accounting for Missing, Unused, and Spurious Data 
The primary analysis will be performed on the collected data. No data imputations will take place, with 
patients with missing data excluded from the analysis. Any spurious data values will be checked against 
source material to verify the validity.  

 
 
 
 
 
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Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
Any deviations from the original analysis plan will be documented and justified in the final analysis 
report.  
Inclusion in Analysis 
All patients who meet the entry criteria will be included in the study. 
 

 
 
 
 
 
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13. 
RISK AND BENEFITS 
 
13.1 Benefits 
The information collected in this clinical investigation will be added to the current knowledge 
and understanding of treatment options for patients requiring ACL reconstruction.  It is 
expected that recipient patients of the JewelACL device will have the same benefits as 
patients implanted with autografts and other commercially available ACL devices used for 
ACL reconstruction.  It will also provide long term outcome data to reassure surgeons of the 
device’s performance. 
A minimum of 5 year follow up data on the JewelACL device will be beneficial to surgeons 
as it will provide assurance of the device’s safety and performance over the long term. 
 
13.2 Risks 
With the review of medical records, the primary risk is that of breach of confidentiality of 
data. All source data is to be held within the reporting hospital site and no identifiable details 
are to be included in any data reports.   
  
13.3 Anticipated Adverse Device Effects 
Adverse events potentially associated with the use of the JewelACL device and potential  
complications are documented in the Instructions for Use.  Instructions for Use are available 
upon request. 
 
13.4 Risk Control Measures 
Actions to control or mitigate risks at the clinical investigation centre will include the 
selection of qualified and experienced investigators.  No patient identifying data will be 
collected for the study.  
 
13.5 Risk to Benefit 

 
 
 
 
 
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The risks associated with the use of the JewelACL device are anticipated to be comparable to 
those associated with the use of other commercially available devices used for ACL 
reconstruction.  Given that the study is retrospective in nature and does not introduce any new 
clinical risks to the patient, the benefit of this study outweighs any risks to the patient. 
 

 
 
 
 
 
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14. 
CLINICAL DATA HANDLING 
The Sponsor will be responsible for the handling of study data.  All study data will be entered on the 
Electronic Case Report Form. 
 
14.1 Direct Access to Source Data/Documents 
Direct access will be granted to authorised representatives from the Sponsor, host institution 
and the regulatory authorities to permit study-related monitoring audits and inspections. 
  
14.2 Protection of Personally Identifiable Information 
The participants enrolled into this study will only be identified by a study specific participants 
number and/or code in any database.  The name or any other identifying details of the 
participant will NOT be included in any study data electronic file.  The privacy of each 
subject and confidentiality of his/her information will be preserved in reports and when 
publishing any data.  Confidentiality of data will be observed by all parties involved at all 
times throughout the clinical study.  All data will be secured against unauthorized access. The 
study will comply with the General Data Protection Regulations. 
  
14.3 Document and Data Control 
 
 
14.3.1 Traceability of Documents and Data 
 
The Investigator will ensure accuracy, completeness, legibility and timeliness of the 
 
data reported to the Sponsor on the CRFs and in all required reports. 
 
 
14.3.2 Recording Data 
 
The CRF will be reviewed by the authorised site personnel.  The data reported on the 
 
CRFs shall be derived from source documents and be consistent with these source 
 
documents, and any discrepancies shall be explained in writing or added as comments 
 
via the CRF. Any change or correction to data reported on a CRF shall be dated, 
 
initialed and explained if necessary, and shall not obscure the original entry (i.e. an 

 
 
 
 
 
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audit trail shall be maintained); this applies to both written and electronic changes or 
 
corrections. 
 
 

 
 
 
 
 
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15. 
MONITORING 
It is the responsibility of the Sponsor to ensure the clinical investigation is conducted, recorded and 
reported according to the approved CIP, subsequent amendment(s), applicable regulations and 
guidance documents. 
The Sponsor will arrange for a monitoring visit once the first ten subjects have been enrolled. A 
subsequent visit will be scheduled, where ten subjects will be randomly selected and then monitored. 
The Principal Investigator or institution will provide direct access to source data during and after the 
clinical study for monitoring, audits, EC review and regulatory authority inspections, as required.  The 
Principal Investigator or institution will obtain permission for direct access to source documents from 
the hospital administration and national regulatory authorities before starting the clinical study. 
 
 

 
 
 
 
 
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16. 
ETHICS 
 
16.1 Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of 
the Declaration of Helsinki.  
  
16.2 Guidelines for Good Clinical Practice   
The Investigator will ensure that this study is conducted in full conformity with relevant 
regulations and with the ICH Guidelines for Good Clinical Practice and in accordance with 
ISO14155. 
16.3 Approvals  
The protocol will be submitted to an appropriate Research Ethics Committee (REC) and host 
institution(s) for written approval.   
The Investigator will submit and, where necessary, obtain approval from the above parties for 
all substantial amendments to the original approved documents.    
 

 
 
 
 
 
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17. 
COMPLIANCE 
 
17.1 Clinical Trial Agreement 
The Investigator will sign a Clinical Trial Agreement and agrees to be compliant with the 
agreement.  The Investigator will not start enrolling patients or requesting verbal consent from 
any subject prior to obtaining EC approval and relevant regulatory approval, if applicable, and 
authorisation from the Sponsor in writing before the clinical investigation. If additional 
requirements are imposed by the EC or relevant regulatory authority, those requirements will 
be followed.  If any action is taken by an EC or a relevant regulatory authority with respect to 
the clinical study, that information will be forwarded to the Sponsor. 
  
17.2 Insurance 
As the Sponsor, Xiros has taken up general liability insurance in accordance with the 
requirements of the applicable local laws.  Insurance certificates/documentation will be 
provided to the Investigator upon request. 
 

 
 
 
 
 
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18. 
SUSPENSION 
OR 
PREMATURE 
TERMINATION 
OF 
THE 
CLINICAL 
INVESTIGATION 
The Sponsor reserves the right to terminate the clinical study at any stage, with appropriate written 
notice to the Investigators, ECs and relevant authorities, if required. 
A Principal Investigator, EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical study at the study centres for which they are responsible.  The Investigators 
will follow requirements specified in the Clinical Trial Agreement. 
The clinical investigation will be concluded when: 
• 
All centres are closed AND 
• 
The final report has been provided to Investigators or the Sponsor has provided formal 
documentation of clinical study closure. 

 
 
 
 
 
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19. 
PUBLICATION 
Publications or presentations of clinical study results may be published in an appropriate journal.   

 
 
 
 
 
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20. 
REPORTING RESULTS ON CLINICALTRIALS.GOV 
This clinical investigation will be registered on ClinicalTrials.gov.  A full report of the pre-specified 
outcomes, regardless of the results, will be made public through ClinicalTrials.gov website no later 
than 12 months after the clinical investigation completion. If this clinical investigation is terminated 
early, the Sponsor will make every effort to hasten the release of the pre-specified outcomes through 
the ClinicalTrials website. 

 
 
 
 
 
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21. 
REFERENCES 
Gans I, et al . Orthop J Sports Med. 2018;6(6):2325967118777823 
LAB 139 8.00   JewelACL Instructions for Use  
JewelACL Clinical Evaluation Report CER 007 revision 02, August 2019 
van Melick N, van Cingel REH, Brooijmans F, et al. Br J Sports Med 2016;50:1506–1515. 
 
 
 
 
 
 
 
 

 
 
 
 
 
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APPENDIX 1  
PATIENT REPORTED OUTCOMES  

IKDC Subjective Knee Evaluation  
 
SYMPTOMS*: 
*Grade symptoms at the highest activity level at which you think you could function without significant symptoms, even if 
you are not actually performing activities at this level. 
 
1. 
What is the highest level of activity that you can perform without significant knee pain? 
 
4 Very strenuous activities like jumping or pivoting as in gymnastics or football 
 
3 Strenuous activities like heavy physical work, skiing or tennis 
 
2 Moderate activities like moderate physical work, running or jogging 
 
1 Light activities like walking, housework or gardening 
 
0 Unable to perform any of the above activities due to knee pain 
 
2. 
During the past 4 weeks, or since your injury, how often have you had pain? 
Never 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Constant 
 
 
 
 
 
 
 
 
 
 
 
 
3. 
If you have pain, how severe is it? 
No pain 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
Worst pain 
imaginable 
 
 
 
 
 
 
 
 
 
 
 
 
4. 
During the past 4 weeks, or since your injury, how stiff or swollen has your knee been? 
 
4 Not at all 
 
3 Mildly 
 
2 Moderately 
 
1 Very 
 
0 Extremely 
 
5. 
What is the highest level of activity you can perform without significant swelling in your knee? 
 
4 Very strenuous activities like jumping or pivoting as in gymnastics or football 
 
3 Strenuous activities like heavy physical work, skiing or tennis 
 
2 Moderate activities like moderate physical work, running or jogging 
 
1 Light activities like walking, housework or gardening 
 
0 Unable to perform any of the above activities due to knee swelling 
 
6. 
During the past 4 weeks, or since your injury, has your knee locked or caught? 
 
0Yes     1No 
 
7. 
What is the highest level of activity you can perform without significant giving way in your knee? 
 
4 Very strenuous activities like jumping or pivoting as in gymnastics or football 
 
3 Strenuous activities like heavy physical work, skiing or tennis 
 
2 Moderate activities like moderate physical work, running or jogging 
 
1 Light activities like walking, housework or gardening 
 
0 Unable to perform any of the above activities due to giving way of the knee 

 
SPORT ACTIVITIES: 
 
8. 
What is the highest level of activity you can participate in on a regular basis? 
 
4 Very strenuous activities like jumping or pivoting as in gymnastics or football 
 
3 Strenuous activities like heavy physical work, skiing or tennis 
 
2 Moderate activities like moderate physical work, running or jogging 
 
1 Light activities like walking, housework or gardening 
 
0 Unable to perform any of the above activities due to knee 
 
9. 
How does your knee affect your ability to: 
 
 
Not difficult 
at all 
Minimally 
difficult 
Moderately 
Difficult 
Extremely 
difficult 
Unable to 
do 
a. 
Go up stairs 
4 
3 
2 
1 
0 
b. 
Go down stairs 
4 
3 
2 
1 
0 
c. 
Kneel on the front of your knee 
4 
3 
2 
1 
0 
d. 
Squat 
4 
3 
2 
1 
0 
e. 
Sit with your knee bent 
4 
3 
2 
1 
0 
f. 
Rise from a chair 
4 
3 
2 
1 
0 
g. 
Run straight ahead 
4 
3 
2 
1 
0 
h. 
Jump and land on your involved leg 
4 
3 
2 
1 
0 
i. 
Stop and start quickly 
4 
3 
2 
1 
0 
 
FUNCTION: 
 
10. 
How would you rate the function of your knee on a scale of 0 to 10 with 10 being normal, excellent function and 0 
being the inability to perform any of your usual daily activities which may include sport?   
 
FUNCTION PRIOR TO YOUR KNEE INJURY: 
 
Couldn’t 
perform daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No limitation in 
daily activities 
 
 
 
 
 
 
 
 
 
 
 
 
 
CURRENT FUNCTION OF YOUR KNEE: 
 
Cannot perform 
daily activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No limitation in 
daily activities 
 
 
 
 
 
 
 
 
 
 
