Investigation on Performance of a New Developed Prosthetic Knee
Phase: NA
Conditions: Amputation
Sponsor: Össur Iceland ehf

date 21.12.2023 NCT06748729

 
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Sponsor 
Principal/Coordinating Investigator 
Össur Iceland ehf 
Grjótháls 3-5 
110 Reykjavík, Iceland 
Name: Kurt N. Gruben 
 
Sponsor’s Statement: On behalf of the Sponsor, I have reviewed and approved this CIM in its entirety and agree 
to sponsor its implementation 
 
Principal Investigator’s Statement: I have reviewed and approved this CIM in its entirety and agree to follow carry 
out its implementation 
Principal Investigator: 
 
Electronical Approval of Document, front 
page/See scanned signature page 
 
Date of Signature: 
 
Electronical Approval of Document, front page/ 
See scanned signature page 
 
 
 
 
 

 
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STATEMENT OF INVESTIGATOR COMPLIANCE 
 
This protocol is a prospectively designed study to investigate the performance of the Navii Knee after technical 
updates. 
● 
Implement and conduct this study diligently and in strict compliance with the protocol, good clinical 
practices (GCP), ISO 14155: 2020 standards, and all applicable laws and regulations. 
● 
Maintain all information supplied by Össur Iceland ehf in confidence and, when this information is 
submitted to an Ethics Committee (EC), it will be submitted with a designation that the material is 
confidential. 
● 
Ensure that all persons assisting with the research are adequately informed about the protocol and their 
research-related duties and functions. 
This document contains confidential information belonging to the Sponsor (Össur Iceland ehf) and therefore, may 
not be disclosed to any other person or entity without the prior written permission of the Sponsor unless such 
disclosure is required by law or regulation. 
 
Investigator Signature  
I have read and understand the contents of the clinical protocol including this Statement of Investigator 
Compliance.  I agree to follow and abide by the guidelines set forth in this document.  
 
 
Principal Investigator Name: Kurt N Gruben 
 
 
__________________________________                                 _____________________ 
 
  
        Principal Investigator Signature  
 
 
               Date 
 
 
 

 
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Table of Contents 
1 
How to Refer to This Document .............................................................. 6 
2 
Summary ................................................................................................... 6 
3 
Changes from Previous Revision ........................................................... 8 
3.1 
Changes for Revision 1.00 ......................................................................................... 8 
4 
Abbreviations ............................................................................................ 8 
5 
Investigational Device .............................................................................. 9 
6 
Justification for the Design of the Clinical Investigation.................... 13 
7 
Objectives and Hypotheses ................................................................... 15 
8 
Design of the Clinical Investigation ...................................................... 18 
8.1 
General .................................................................................................................... 18 
8.2 
Investigational Device(s) and Comparator(s) ........................................................... 19 
8.3 
Subjects ................................................................................................................... 19 
8.4 
Procedures .............................................................................................................. 22 
i) 
Recruitment ............................................................................................................................. 22 
ii) 
Test procedure ......................................................................................................................... 22 
iii) 
Measurements and data collection .......................................................................................... 22 
8.5 
Compensation .......................................................................................................... 23 
8.6 
Responsibilities ........................................................................................................ 24 
8.7 
Study monitoring and Oversight ............................................................................... 24 
9 
Investigational Device Accountability .................................................. 24 
10 
Statistical Considerations ..................................................................... 25 
10.1 
Statistical design and procedures ............................................................................ 25 
10.2 
Sample size calculation ........................................................................................... 25 
11 
Amendments and Deviations from the Protocol (CIP) ........................ 25 
11.1 
Amendments ............................................................................................................ 25 
11.2 
Deviations ................................................................................................................ 25 
12 
Statement of Compliance ...................................................................... 26 
13 
Ethical Considerations ........................................................................... 26 
13.1 
Anticipated clinical benefits ...................................................................................... 26 
13.2 
Device related risk ................................................................................................. 26 
13.3 
Risk of Study (To Patient) ..................................................................................... 28 
13.4 
Risk Mitigation ....................................................................................................... 28 
13.5 
Risk-to-Benefit Rationale ...................................................................................... 28 
13.6 
IRB/REB/REC Review and Communications ....................................................... 28 
13.7 
Vulnerable populations ......................................................................................... 28 
13.8 
Informed Consent .................................................................................................. 28 
13.9 
Participant confidentiality – Data management .................................................. 29 
14 
Evaluation of Adverse Events and Device Deficiencies ..................... 31 
14.1 
Definitions of adverse events, effects and deficiencies ..................................... 31 
14.2 
Reporting procedures ........................................................................................... 31 
14.3 
Suspension or premature termination of the clinical investigation .................. 32 
15 
Publication Policy ................................................................................... 32 

 
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16 
References .............................................................................................. 32 
17 
Annex ...................................................................................................... 34 
 
Tables 
Table 1 Summary of procedures and visits ......................................................................................................... 8 
Table 2 Identification and Description of the Investigational Device ................................................................ 9 
Table 3 Technical and functional features ......................................................................................................... 12 
Table 4 - Claims/MNBA items to be evaluated ................................................................................................... 15 
Table 5 - Phase I Endpoints, test methods and hypotheses ............................................................................ 16 
Table 6 Inclusion/Exclusion criteria ................................................................................................................... 21 
Table 7 Visit schedule and procedures .............................................................................................................. 23 
 
 
 

 
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1 How to Refer to This Document 
2 Summary 
Device(s) being 
tested: 
Device under evaluation: Navii (also known as Rheo Knee 4), a pre-market 
passive exo-prosthetic microprocessor controlled knee device.  
Comparator: Subjects prescribed passive microprocessor knee, marketed device. 
For simplification the device under evaluation in this investigation will be referred to 
as “investigational device” throughout this document. 
Instruments and 
equipment: 
Instruments: 
 
SFCS Socket fit comfort score 
 
PEQ ambulation subscale (Questions 13A, 13B, 13C, 13D, 14E, 14F, 14G, 14H) 
 
PEQ Utility questions (Questions 2G, 2F) 
 
PEQ Satisfaction Questions (Questions 16A, 16B) 
 
Device and performance specific questionnaires 
 
TUG, 2MWT, ABC, PLUS-M.  
Equipment: 
 
Investigational device (see section 5 Investigational device) 
 
Other components as applicable (prosthetic feet, adapters) 
 
Tools for fitting 
 
Detailed protocol 
 
Case report forms (CRFs); in Smart-Trial – Tablet/computer OR Printed out 
Case report forms (CRFs including instruments listed above) 
Subjects recruited: 
Inclusion criteria: 
Exclusion criteria: 
 
‐ 
45Kg< body weight < 136Kg  
‐ 
Cognitive ability to understand all 
instructions and questionnaires in the 
study;  
‐ 
Unilateral TF/KD amputees that are 
regular prosthesis users for at least 3 
months 
‐ 
Current MPK users (passive MPKs 
only) regularly performing descent 
activities (stairs/ramps) 
‐ 
Age ≥ 18 years  
‐ 
Willing and able to participate in the 
study and follow the protocol 
‐ 
Users with stump pain 
‐ 
Users with socket problems 
‐ 
Pregnant Users  
‐ 
Users using Power Knee, Kenevo or 
mechanical knees as their prescribed 
prosthesis 
‐ 
Alignment that cannot be matched 
with the Navii setup, as described in 
Instructions for use.  
‐ 
Osseointegration 
Procedures: 
There are two scheduled study events. Up to 13 users will be recruited (Up to 10 
Rheo Users and up to 3 other MPK Hydraulic Users), 1 study site. At the initial visit, 
the first study event, for each subject a researcher qualified to obtain informed 
consent will seat the subject and proceed as described in chapter 13.8 Informed 

 
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consent. 
Prior to fitting the subject will be asked to provide feedback on the current 
prosthesis, by filling in a set of questionnaires (including subset of PEQ) and perform 
tasks of daily living like e.g., walking up/down ramps and stairs, level ground walking 
in different speeds and walking on uneven terrain.  
The users will be fitted within the standard methods of prosthetic fitting and 
alignment will be documented. 
After initial fitting of the investigational device, the subjects will receive standard 
training on the investigational device. The required training steps and exercises as 
well as the performance of the subject will be observed. Comments and initial 
feedback from the subject will be documented. When the training is completed, and 
subjects feel comfortable and safe they will take a short break. Afterwards they will 
be asked to perform the same tasks as with their prescribed prosthesis before. 
A standardized set of questions regarding the performance of the investigational 
device and the subject´s satisfaction will be asked as a semi-structured interview, 
and the responses are documented. After the first feedback round with the 
investigational device, different modes for descent acitivities may be tested.  
The investigator may change the modes and settings. The changes might be subtle; 
subjects will be asked if they feel a difference. Eventually the subjects shall evaluate 
if they prefer a mode. 
The activities are video recorded to visually compare the performance of the two 
devices. 
If the user feels comfortable and safe, he will be asked to use the investigational 
device for 4 weeks. They will be asked to fill in a log file for e.g. use in water, use of 
the app, use of the locking function. 
The LPI will contact the user after 2 weeks to check on any issues that may arise. 
The user has the option to stop the trial at any time, an appointment will be made to 
switch to the prescribed knee. 
The second visit will be at 4 weeks after visit 1. During this visit subjects will 
complete the same functional tests and questionnaires as at visit 1 (excluding 
background information) on the investigational device. They will then be fitted back 
to their prescribed device. 
See Table 1 below. 
Objective 
In this trial, the primary objective is to evaluate the efficacy of the investigational 
device compared to the former Version Rheo Knee (XC) and in addition (mandatory) 
to other passive MPKs (e.g. C-leg 4, Genium, X3, Plié 3, Orion 3, Quattro, Allux) 
regarding performance improvements and satisfaction in descending activities for 
moderate to high active prosthesis users within the intended population for the 
investigational device. 
Additionally,  the overall satisfaction for activities of daily living will be evaluated after 
a certain time of use (4 weeks home use).   
 
 
 
 
 
 

 
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CRO 
Clinical Research Organisation 
CT 
Clinical Trial 
CTA 
Clinical Trial Authorisation 
EC 
Ethics Committee (see IEC, IRB, REB and REC) 
EDS 
Electronic Data capture Service 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
CIB 
(Clinical) Investigator Brochure 
ICF 
Informed Consent Form 
IDMF 
Investigational Device Management Form 
IEC 
Independent Ethics Committee 
IFU 
Instructions For Use 
IRB 
Independent/Institutional Review Board 
LCI 
Local Co-Investigator 
LPI 
Local Principal Investigator 
LRA 
Local Research Assistant 
PI 
Principle Investigator 
PIS 
Participant Information Sheet 
REB 
Research Ethics Board 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Event 
SOP 
Standard Operating Procedure 
SOTA 
State-Of-The-Art 
SRA 
Sponsor Research Assistant 
USADE 
Unanticipated Serious Adverse Device Effect 
 
5 Investigational Device 
The investigational device is a pre-market device and will be labeled according to regulations concerning pre-
marketed investigational devices. 
See Table 2 for details on the investigational device. 
Table 2 Identification and Description of the Investigational Device 
Summary description of 
the investigational 
device and its intended 
purpose: 
The investigational device, Rheo Knee 4 which will be marketed under the name 
NAVii, is a passive microprocessor-controlled prosthetic knee. It is a Class II product 
and is a further development of a well-established technology. 
 
The device is classified as an “External assembled lower limb prosthesis” according 
to Title 21 §890.3500, bearing the product code ISW (Assembly, 
Knee/Shank/Ankle/Foot, External) 
 
It is 510(k) exempt, except for general requirements. 
 
It is composed of a microprocessor-controlled prosthetic knee, a power supply and a 
configuration software. Sensors within the prosthetic knee prosthesis provide 
continuous real-time information. This data is utilized to control the braking torque of 
the joint via activating a magnetorheological actuator. Via the configuration software, 
running on an external computing device, a wireless link to the prosthetic knee 
prosthesis can be established. Through this the investigational device can be 
optimized with respect to the end users’ gait, physical characteristics and personal 

 
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preferences.   
The investigational device supports prosthetic use from simple locomotion to 
ambulation with variable cadence and traverse of various terrains. Additionally, it 
offers features as step-over-step stairs and ramp walking, running, and cycling. 
Exo-prosthetic devices are by their nature non-invasive. The investigational device is 
a non-sterile, reusable (i.e. non-disposable), single user device, which is used as part 
of prosthetic system. 
 
The Investigational device is a programmable electrical medical system (PEMS). Its 
essential performance is defined as structural support, as loss of structural support 
does not allow the device to fulfill its intended use. Loss of the PEMS related 
operation on the other hand allows the user to continue walking even if the 
performance and feature set provided by the device are reduced.  
The Investigational device is an internally powered device when operated in its 
intended medical purpose.  
Device Intended purpose: 
The Investigational device is intended as part of a prosthetic system that replaces 
knee function of a missing lower limb. 
Manufacturer of the 
investigational device: 
Össur hf. 
Grjothals 5 
110 Reykjavik 
Iceland 
Name or number of the 
model/type, including 
software version and 
accessories, if any, to 
permit full identification: 
Model: NAVII 
 
 
Traceability during and 
after the investigation:  
Investigation Device Management Form (IDMF) will be used to track the use of each 
device within the clinical investigation using the device serial number. 
Intended purpose of the 
investigational device in 
the proposed clinical 
investigation: 
Intended purpose of the investigational device in the proposed clinical investigation is 
within the intended purpose as described above. 
See following chapters on the intended purpose of the investigational device in the 
proposed clinical investigation for details. 
The populations and 
indications for which the 
investigational device is 
intended: 
Intended Purpose Statement 
The device is intended as a part of a prosthetic system that replaces knee function of 
a missing lower limb. 
Indications for Use(s) 
Lower limb loss, amputation or deficiency.  
Contraindications for Use(s) 
No contraindications for use are known for Navii / Rheo Knee 4. 
Intended Patient Population 
Medical conditions: 
Transfemoral / knee disarticulation amputation; 
Activity Level: 
Moderate to high-active ambulators 
- 
Community ambulators; 

 
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- Ambulation exceeding basic ambulation needs or 
skills. 
Impact Level: 
Low to high impact levels. 
User Weight: 
Higher than 45kg; 
 
Lower than 136kg (110kg for high impact use). 
 
Description of the 
investigational device: 
See Table 3 below for descriptions of device features and their relation to the 
investigation. 
 
Figure 1 Investigational device as final product 
 
The investigational device is composed of a microprocessor-controlled prosthetic 
knee, a power supply and a configuration software. Sensors within the prosthetic 
knee provide continuous real-time information. This data is utilized to control the 
braking torque of the joint via activating a magnetorheological actuator. Via the 
configuration software, running on an external computing device, a wireless link to 
the prosthetic knee prosthesis can be established. Through this the investigational 
device can be optimized with respect to the end users’ gait, physical characteristics 
and personal preferences.   
The aspect of the prosthesis that is in direct physical contact with the amputee is 
usually a liner that serves as an interface between the amputee and the rest of the 
prosthesis. In other words, the device is usually not in direct physical contact with the 
amputee. 
 
As described above, the device is intended to be in contact with intact skin only. 
 
The device does not incorporate, as an integral part, a substance or human blood 
derivative and is manufactured without utilizing tissues of animal origin. 
 
Summary of the 
necessary training and 
experience needed to 
use the investigational 
device: 
Training requirements for subjects and procedures relating to fitting and use of a 
device will for all general purposes be equivalent to the training and procedures 
required for using a FDA approved/CE-marked device of a similar type. 
The device should be supplied and fitted by a certified CPO/CO/CP. 
 

 
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For the purpose of this investigation training for subjects will be standardized to 
assure that all subjects will receive the same training.  
Specific medical or 
surgical procedures 
involved in the use of 
the investigational 
device: 
N/A 

 
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6 Justification for the Design of the Clinical Investigation  
The term microprocessor-controlled (MPC) refers to components that are intelligently regulated in real time by 
one or more onboard microprocessors that modify some characteristic of their behavior according to either 
environmental or user inputs.1 MPC prosthetic knees, often referred to as MPKs, are battery-powered and use 
algorithms based on input received from load sensors, accelerometers, gyroscopes, and joint angles to initiate 
the transition from stance to swing phase 2-6. MPC prosthesis have been shown to offer clinical advantages 
compared with mechanically controlled alternatives,7 and appears to be the direction of development in 
contemporary prosthetic research and development.8  
The main advantage is an increased ability to allow safe ambulation 2,4,5,9-11, reduced cognitive dedication to 
controlling the knee unit,2,12 reduced force required to initiate knee flexion,10 increased gait efficiency,2,4 and 
increased overall user confidence with the prosthesis 2,5. The MPC knee increases comfort and improves walking 
speed in active users. 4,6,13,14, The main disadvantage has been the intolerance of dust or moisture, and its 
increased requirement for maintenance and repair.15  
Microprocessor Controlled Knees (MPK) have become the standard of care for trans-femoral amputees of 
medium to high activity levels (K3-K4). While the functional principles of the different knee joints remain the 
same, differences in the mechanical design can be found.  
The investigational device is a microprocessor-controlled prosthetic knee and employs sensory information, to 
automatically adapt knee damping values to match the amputee’s gait requirements, accounting for variations in 
forward walking speed, walking terrain, user gait styles and body size. The investigational device technology 
generates resistances with a microprocessor-controlled, magnetorheological fluid, which enables continuous 
variation of knee joint resistances in both movement directions. The amount of current determines the viscosity 
of the fluid. Therefore, an adaptable friction moment is generated for both flexion and extension movements at 
the same time. In this study there are two types of comparator devices, hydraulic MPKs and previous version of 
the investigational device.  
 
Hydraulic MPKs consist of an integrated microprocessor-controlled linear hydraulic system in combination with a 
control algorithm. They generate knee joint resistances hydraulically with microprocessor-controlled, motorized 
valves. This enables continuous variations in the hydraulic resistance to be set for both movement directions. 
The magnetorheological fluid creates shear forces in comparison to an increase of pressure in a hydraulic 
system. The increased system pressure can lead to higher temperatures and risk of leakage. 
 
The previous version of the investigational device (RK III/RK XC) features the same intended use, same clinical 
purpose, same user population, same placement below the socket, uses a battery powered system and is 
controlled through a software application that can be user configured through a separate computer 
interface/mobile device. The investigational device is an enhancement of the previous version, functional 
features and indication are equivalent to previous version and the same critical functions apply. Features that 
have been added include a mechanical stance locking feature that allows the user to manually lock the knee in 3 
different positions in stance and the device will be waterproof. The investigational device also includes functions 
that were only included in the Rheo Knee XC configuration of the previous version; automatic cycling and 
running detection and a stair ascent mode.  
Results of a pilot stage exploratory clinical investigation including 25 subjects indicate that the investigational 
device had similar or better performance compared to previous versions of the Rheo knee regarding satisfaction 
on descending activities. This investigation is designed primarily to confirm these indications and that the 
performance of the investigational device regarding descending activities is comparable/no worse than Rheo 
Knee or hydraulic MPKs.   
 
 

 
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Study Design 
 
 
Figure 2 - Study design and instruments 
Repeated measures analysis has the advantage of increased power compared to group allocations and 
reduction in error variance associated with individual difference, as each subject acts as its own control. This is 
important for studying amputees as the group is a small proportion of the total population, and with specific 
inclusion/exclusion criteria the total eligible population becomes very small, making it difficult to find and recruit 
subjects to attain an acceptable level of power. This limited population pool often results in a slightly 
heterogeneous sample, as the amputees available are few and far between, in every sense. Furthermore, no 
single amputation procedure and therefore amputated stump is exactly the same, making the experience of each 
amputee unique. The within-subject design significantly reduces the individual differences when comparing the 
two conditions. 

 
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8 Design of the Clinical Investigation 
8.1 General 
The test will be a non-randomized single group repeated measures open label prospective design with 
observational and self-report measures. 
Amputees are a small proportion of the general population. The population group specified in the 
inclusion/exclusion criteria is a further subsample of amputees. For practical reasons, i.e. to achieve statistical 
power, it is therefore more feasible to use within-subject comparison rather than creating study arms to compare. 
Furthermore, as mobile amputees generally have and use a prosthetic device for their daily activities, within-
comparison is feasible comparing to the subject’s previous device. 
All investigational activities will be conducted at the Össur Orlando site.  
As stated above the primary endpoint is Satisfaction on descending stairs, see Table 5, and the secondary 
endpoints are satisfaction on descending ramps, balance confidence and standing comfort in that respective 
order of significance. In addition, there are two exploratory endpoints on mobility and balance during ambulation. 
See previous chapter on objectives and hypothesis and Table 5 for rationale. 
Drop-outs and withdrawals will not be replaced. 
Instruments for data collection will include the following:  
The Prosthesis Evaluation Questionnaire (PEQ) measures prosthetic-related quality of life. It consists of 82 items 
grouped into nine subscales. In addition, there are individual questions not contained in the subscales regarding 
satisfaction, pain, transfers, prosthetic care, self-efficacy, and importance18. This study will include a set of 
subscales from the PEQ, including specific questions on descending activities. 
TUG The Timed Up and Go (TUG) is a tool used to test basic mobility skills by asking the subject to stand up 
from a chair (which should not be leaned up against a wall), walk a distance of 3 meters, turn around, walk back 
to the chair and sit down 
2MWT is a measurement of endurance that assesses walking distance over two minutes. 
ABC is a Patient-reported outcome measure that asks individuals to rate how confident they are that they will not 
lose their balance while performing 16 different activities. 
PLUS-M (Prosthetic Limb Users Survey of Mobility) is a self-report instrument for measuring mobility of adults 
with lower limb amputation. 
Specific questionnaire: In-house generated questionnaire on specific features in the investigational device. 
Log file: User should log device use and events. 

 
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Video 
Data logging by Össur Logic 
See chapter 10.2 Sample size calculation for analysis of variables. 
Equipment required for each subject: 
 
Investigational device  
 
Other components as applicable (prosthetic feet, adapters) 
 
Tools for fitting 
 
Detailed protocol 
 
Case report forms (CRFs) in Smart-Trial – Tablet/computer OR Printed out Case report forms (CRFs 
including instruments listed above) 
 
The equipment used does not require specific monitoring, maintenance, or calibration procedures.  
8.2 Investigational Device(s) and Comparator(s) 
The subjects will be asked to use the investigational device as their primary prosthesis for 4 weeks. Individual 
exposure will differ between subjects. Subjects are expected to use it for their daily living activities as they would 
with any other prosthesis, for up to 18 hours a day depending on the amputee. The comparator device will not be 
used within the timeframe of the investigation. Subjects will evaluate and provide feedback on their exposure of 
the comparator prior to them being fitted to the investigational device. 
The comparator device will be the former version Rheo Knee (XC) or any other passive microprocessor 
controlled prosthetic knee (excluding Kenevo as it does not have the same intended patient population as the 
investigational device). They have the same intended use as the investigational device. Furthermore, they are 
indicated for the same condition and population group. Passive MPKs are widely accepted devices, providing 
clinical benefits to the user.  
Where possible, the subject will be using the remaining part of their current prosthetic system with the 
investigational device, as it was used with the comparator device. In some cases where a subject is using 
components from other manufacturers (e.g. feet not validated for use with the investigational device) compatible 
components will be provided.  
No other device, medication or intervention will be used. 
 
Up to 13 subjects are to be enrolled and therefore 13 investigational devices will be used, as the devices are 
intended to be used by a single patient; one for each subject. 
 
 
8.3 Subjects  
All subjects will be dispositioned as follows: 
 
Screen Failure: Subject did not pass screening procedures, not called in for clinical visit; 
 
Candidate for enrollment: Passed screening procedures, accepts to come in for clinical visit; 
 
Enrolled: Subject signs informed consent and takes part in the first experimental session; 
 
Fitted: Subject leaves the clinic on the investigational device; 
 
Drop-out: Enrolled subject whose participation ended because they did not want to continue 
participation. 
 
Discontinued: Candidate for enrollment or Enrolled subject whose participation ended because they 
withdrew consent, were withdrawn by the Investigator, were lost to follow up, or died. 
 

 
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Table 6 Inclusion/Exclusion criteria 
Inclusion: 
Only patients with the following characteristics 
are eligible for study entry: 
Exclusion: 
Patients with the following characteristics are 
not eligible for study entry: 
45Kg< body weight < 136Kg  
Users with stump pain* 
Cognitive ability to understand all instructions 
and questionnaires in the study;  
Users with socket problems** 
Unilateral TF/KD amputees that are regular 
prosthesis users for at least 3 months 
Pregnant Users***  
Current MPK users (passive MPKs only) 
regularly performing descent activities 
(stairs/ramps) 
Users using Power Knee, Kenevo or mechanical 
knees as their prescribed prosthesis 
Age ≥ 18 years  
Alignment that cannot be matched with the Navii 
setup, as described in Instructions for use.  
Willing and able to participate in the study and 
follow the protocol  
-Osseointegration  
*Question on pain affecting their functional ability (yes/no) 
**Socket fit: Socket fit comfort score over 5 
*** Self reported 
A subject can withdraw from participation at any time, at his/her discretion, and this will not have any 
consequences for the participant’s treatment. In such cases a report stating reasons for discontinuation of the 
participant shall be prepared by the LPI. No further investigational procedures concerning the subject will be 
conducted, except for a statement explaining the reason for withdrawal, including but not limited to: interacting or 
interviewing the subject in order to obtain data on him/her; obtaining additional private information on the subject 
by either observing the subject or collecting or receiving such information from any source. 
The LPI can withdraw the participant from the trial at any time. The reasons shall be documented. There are no 
pre-specified criteria for discontinuation of participants from the trial. The discontinuation of participants in the 
trial will not result in replacement with new participants. If withdrawal is due to problems related to the 
investigational device the participant will be asked for permission to follow the status/condition outside the clinical 
investigation. The follow-up will be individualized. 
Screening will be supported by Össur customers (prosthetic clinics) with potential for users fitting into the 
inclusion criteria. 
Enrollment will take place at the Össur site in Orlando. 
The total time period required to implement the clinical investigation is expected to be 12 weeks. Each individual 
subject is expected to participate in the clinical investigation for 4 weeks. The estimated time needed to include 
this number (enrolment period) is 6 weeks. 
At least 10 subjects are required to finish the protocol for statistical data analysis, as specified in chapter 10.2 
Sample size calculation. 

 
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8.4 Procedures  
i) Recruitment 
Potential subjects will be identified from the selected customer base of Össur. Customer representative 
evaluates, based on previous experience of interaction with and servicing of patients, if a potential participant is 
cognitively capable. The customer representative informs the PI / LPI of the potential subject and hands over 
their contact information. If a potential participant fits the inclusion and exclusion criteria the LPI will contact them 
via telephone. During the telephone call the LPI will verify if they are interested in participating in a study. If 
interest is expressed at that point they will answer some screening questions and if the eligibility criteria are met 
an appointment will be made for the clinical visit and signing of the ICF. Questions relating to the duration of the 
study, number of clinical visits required, and the investigational device will be answered. 
Potential risk of participating in the investigation will be explained to the subject at this point to the candidate for 
enrolment. 
The LPI will communicate to the study monitor the number of users he has identified that meet the inclusion 
criteria and are willing to participate. 
ii) Test procedure 
There are two scheduled study events. Up to 13 users will be recruited, 1 study site. At the initial visit, the first 
study event, for each subject a researcher qualified to obtain informed consent will seat the subject and proceed 
as described in chapter 13.8 Informed consent. 
Prior to fitting the subject will be asked to provide feedback on the current prosthesis, by filling in a set of 
questionnaires (including subset of PEQ) and perform tasks of daily living like e.g., walking up/down ramps and 
stairs, level ground walking in different speeds and walking on uneven terrain.  
The users will be fitted within the standard methods of prosthetic fitting and alignment will be documented. 
After initial fitting of the investigational device, the subjects will receive standard training on the investigational 
device. The required training steps and exercises as well as the performance of the subject will be observed. 
Comments and initial feedback from the subject will be documented. When the training is completed, and 
subjects feel comfortable and safe they will take a short break. Afterwards they will be asked to perform the 
same tasks as with their prescribed prosthesis before. 
A standardized set of questions regarding the performance of the investigational device and the subject´s 
satisfaction will be asked as a semi-structured interview, and the responses are documented.  
The activities are video recorded to visually compare the performance of the two devices. 
If the user feels comfortable and safe, he will be asked to use the investigational device for 4 weeks. They will be 
asked to fill in a log file for e.g. use in water, use of the app, use of the locking function. 
The LPI will contact the user after 2 weeks to check on any issues that may arise. The user has the option to 
stop the trial at any time, an appointment will be made to switch to the prescribed knee. 
The second visit will be at 4 weeks after visit 1. During this visit subjects will complete the same functional tests 
and questionnaires as at visit 1 (excluding background information) on the investigational device. They will then 
be fitted back to their prescribed device and feedback will be collected. 
 
iii) Measurements and data collection 
The same questionnaires, consisting of one valid instrument (subset of PEQ questions) and device and 
performance specific questionnaires, will be used and filled in at two separate points in time. Background 
information will be collected at baseline only. An activity report will be generated from the investigational device 
at visit 2. 
 
 
 
 

 
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8.6 Responsibilities 
Principal Investigator (PI) / Local Principal Investigator (LPI) 
 
Screen subjects 
 
Explain trial to participants 
 
Responsible for obtaining informed consent from test subjects 
 
Conduct trial procedures  
 
Fit users with trial device and provide training and back to their current prosthesis 
 
Investigate possible vigilance cases/SAEs 
 
Technical support 
Co-Investigators (CI) 
 
Explain trial to participants 
 
Obtaining informed consent from test subjects 
 
Conduct trial procedures  
 
Fit users with trial device and provide training and back to their current prosthesis 
 
Collect Data 
 
Technical support 
Monitor 
 
Train site staff on study procedures 
 
Monitor trial 
 
Analyze results 
 
Write report 
Sponsor Research assistants (SRA) 
 
Technical support 
 
Support in data collection 
8.7 Study monitoring and Oversight 
The study monitor(s) will monitor the study to ensure all procedures are followed correctly and according to the 
study protocol. The study monitor will gather and review all study data and inform the PI of missing data or 
nonconformities to the study protocol. 
The study monitor(s) and PI will maintain communication on a minimum biweekly basis, via telephone and email. 
The PI will provide the study monitor(s) with information of all scheduled study visits. The study monitor will visit 
each investigational site at least once while a study visit takes place. 
9 Investigational Device Accountability 
The investigational device will be provided as needed for the study population. Devices will not be packaged but 
will be labeled according to FDA regulatory requirements. Subjects will not be blinded. 
The PI will keep records documenting the receipt, use and return of the investigational device in the 
Investigational Device Management Form, including: 
 
Date of receipt 
 
ID of each investigational device 
 
Step count at start and end of investigation 
 
Period of use 
 
Subject ID 
 
Date of device return 
 
Date of return of unused, expired or malfunctioning investigational devices, as applicable 

 
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10 Statistical Considerations 
10.1 Statistical design and procedures 
The primary hypothesis will be assessed with descriptive statistics only, comparing the rates prior-evaluation 
(current device) and post-evaluation (investigational device). For hypotheses B, C, D, E will be assessed with 
mixed models effects where MPK type is used as fixed effect, subgroup analysis, and subject as random effect. 
F will be assessed with exploratory methods. All data will be analyzed exploratively for subgroup effects for input 
into further studies but not used to support claims.  
 Acceptance criteria for the data, as applicable, is defined in Table 4 Endpoints, test methods and 
hypotheses. Subgroup analysis will not be performed as no subgroups are defined. 
10.2 Sample size calculation 
A convenience sample of up to 13 subjects are expected to complete the procedures. 
For pass/fail criteria, see Table 4 Endpoints, test methods and hypotheses. 
11 Amendments and Deviations from the Protocol (CIP) 
11.1 Amendments 
Any amendments to this protocol must be first approved by the sponsor and PI, or LPI for single site studies, and 
then be evaluated by the IRB/REB/REC and, where appropriate regulatory authorities, before being 
implemented. 
For non-substantial changes (e.g. minor logistical or administrative changes, change of monitor(s), telephone 
numbers, renewal of insurance) not affecting the rights, safety and well-being of human subjects or not related to 
the clinical investigation objectives or endpoints, a simple notification to the IRB/REB/REC and, where 
appropriate, regulatory authorities can be sufficient. 
11.2 Deviations 
Investigators are not allowed to deviate from this protocol without a formal approval from the IRB/REB/REC, if 
the deviation affects subject's rights, safety and wellbeing, or the scientific integrity of the clinical investigation. 
Any such deviation from the protocol is to be documented in detail and the report sent to the IRB/REB/REC.  
Under emergency circumstances, deviations from the protocol to protect the rights, safety and well-being of 
human subjects may proceed without prior approval of the sponsor and the IRB/REB/REC. Such deviations shall 
be documented and reported to the sponsor and the IRB/REB/REC as soon as possible. 
Investigators can request for an approval from the sponsor for a deviation if the deviation does not affect 
subject's rights, safety and wellbeing, or the scientific integrity of the clinical investigation. 
In case of a deviation from this protocol taking place without prior approval from the sponsor, and IRB/REB/REC 
as applicable, it shall be reported to the sponsor within 24 hours of LPI knowledge of the deviation. The LPI 
responsible for the deviation is to send a report to the sponsor no later than five days after the deviation was 
reported. The report shall include: 
 
Reason for deviation 
 
When deviation took place 
 
Circumstances of the event 
 
Identification of all subjects affected by the deviation, if any 
o 
Details how each subject is affected, e.g. rights, safety or wellbeing 
 
Details how this deviation might affect the scientific integrity of the clinical investigation 

 
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- 
Memory failure (user forgets clinicians’ training/advice). 
- 
Nascent Error (user performs well meant "optimization", short-cut or improvisation to unusual 
circumstances). 
- 
User performs activity which subjects  the investigational device to undue mechanical stress (jumping off 
a wall for example). 
- 
Dropping the  investigational device (when removing their prosthesis amputees often lean their 
prosthesis up against a wall which frequently resulting in the limb falling to the ground). 
- 
User does not charge the prosthetic knee. 
- 
User does not have good control over the residual limb. 
 
For a list of foreseeable adverse events and anticipated adverse device effects, together with their likely 
incidence, mitigation or treatment see Chapter 7, and applicable annexes, in the Clinical Investigator´s Brochure 
[2]. 
13.3 Risk of Study (To Patient) 
At each visit a LPI, a certified CPO/CP or clinician, will be present to ensure the safety of the participants. The 
study adds no additional risk other than the risks identified above. Subjects will use the trial device as their 
primary prosthesis in the same manner as they would normally do on their current prosthesis. Thus, they are not 
required to do anything different from their routine clinical visit for acquiring a new MPK (the investigational 
device) and their daily living activities between study visits. 
13.4 Risk Mitigation 
For each device designed by Össur risk mitigation is part of the design process according to ISO 14971 [5] [4]. 
Furthermore, each participant fitted with the investigational device (Navii/Rheo Knee 4) for the first time, will 
be trained by a fully qualified professional until the user can demonstrate sufficient understanding of the product 
operation and demonstrate minimum ability level in its operation. This process is the same as the usual training 
process deployed for normal fitting of a MPK device.  
As part of the training process, the participant will be informed on the risks inherent in using an investigational 
MPK device in an uncontrolled environment. Moreover, the participant will be provided with the product literature 
(e.g. Information for User), as well as being informed and trained on how to use the product. 
13.5 Risk-to-Benefit Rationale 
The residual risks of the investigation and the investigational device are minimal and are significantly out 
weighted by the benefits of participating in the investigation. 
13.6 IRB/REB/REC Review and Communications 
The study protocol (CIP), informed consent form, and other study documentation forms require IRB review and 
approval. Communication to and from the IRB shall be directed from or to the primary Össur contact, the 
Sponsor co-investigator/Monitor. Continuous communication will be maintained between Össur and the IRB, 
as required. Moreover, communication will be maintained between the LPIs and PI and the IRB, as required. 
13.7 Vulnerable populations 
No vulnerable populations will be enrolled.  
13.8 Informed Consent 
The Local Principal Investigator (LPI) at each site, or any researcher qualified, will obtain from the subject, 
written signed informed consent form to his/her inclusion in the study, after explaining the rationale for and the 

 
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details of the study, the risks and benefits of alternative treatments, and the extent of the subject's involvement. 
The subject will receive a copy of the informed consent.  
The protocol consists of different phases, subjects will consent only for the phase they participate in. Signing the 
ICF only applies to the current phase, for each phase the ICF will be signed again by each subject. If a subject 
participates in one phase it does not mean they have to participate in the other phases. Enrollment for each 
phase is separate. 
The subjects will be informed that their participation is voluntary and that they can withdraw from participation at 
any time, at his/her discretion and this will not have any consequences for the participant’s treatment. 
In case the information on the ICF changes, and subjects need to be provided with new information, the LPI will 
contact each subject by phone and explain the new information as required. If the study must be postponed until 
IRB approval of the amendment is obtained this will be explained to the patient. 
Subjects that for any reason are unable to provide informed consent will not be enrolled in the study. 
13.9 Participant confidentiality – Data management 
a)  Subjects will be assigned a study identification (ID) number. This ID will be used in all relevant 
documentation. Confidentiality of all relevant subject feedback and information will be maintained through use of 
the identifying number only, in all documentation. The study sponsor, Össur, will remain the sole owner of the 
study data.  
Data will be collected and stored either through the Electronic Data Capture (EDS) system Smart-Trial, or via 
paper based CRFs.  
A list connecting the ID to the subject ́s name will be stored either in the Electronic Data Capture (EDS) system 
Smart-Trial or in a locked file with the LPI at each site. Only appropriately qualified individuals designated by the 
Investigator will have access to this information. Access is controlled by password protected accounts. Accounts 
are enabled with designated permissions only. 
b)  Physical source data (e.g. signed Informed Consent forms and paper based forms as applicable) will reside in 
the Local Principal Investigator Site File. This will be physically locked and accessible to the Investigator only. 
c)  Case report forms in Smart-Trial are developed in accordance with this protocol and are quality checked 
against the protocol by the study team before use, the same is true in case of paper-based CRFs. In Smart-Trial, 
validated fields and reference rules are used to control quality of data on entry and where required the order of 
data collection. In case of paper based CRFs they are reviewed by the investigator and a study monitor to 
ensure completeness of data.  
Data that are missing or collected out of timeframe will be flagged. Smart-Trial contains audit history and data 
query functionality, in case of paper based CRFs, data queries are raised by the investigator or study monitor. 
Data queries may be raised ad hoc or at scheduled monitoring visits. Data queries may be reconciled by 
designated individuals (by account permissions in Smart-Trial) only. Where physical records are used these will 
be stored as source data in the investigator site file and attached to Smart Trial forms as scans if applicable. 
d)  The Smart-Trial system is validated as per the Össur QMS Software Validation process PR-00037 [7] 
reported in VAL1825 [8]. The validation of the software system consists of review of Smart Trial company 
validation records. The validation of individual case report forms against the study protocol is performed by the 
study team and recorded. 
e)  In case of electronic data collection; SMART-TRIAL (www.smart-trial.com) will be used as the primary 
Electronic Data Capture tool in this study. SMART-TRIAL is designed and developed in compliance with the 
PIC/S Guidance, PI-011-3 Good Practices for Computerized Systems in Regulated “GxP” Environments, with 
software validation based on IEC 62304. SMART-TRIAL is designed to enable the user to comply with Good 
Clinical Practice (ISO 14155:2020), ICH GCP and other industry requirements, such as FDA 21 CFR Part 11 and 
HIPAA. f) All data in SMART-TRIAL is collected, transferred, and stored encrypted in databases, which are 
hosted on Microsoft Azure ISO certified servers that are managed by SMART-TRIAL within the European Union 
(Dublin, Ireland). Backups are performed continuously throughout the day and stored within the same server. 
Given that Smart-Trial does send messaging to patients in research studies, as part of the informed consent 
process, (as reviewed  by  the  IRB),  patients  will  be  asked  to  consent  to  communications through these 
channels. Smart-Trial is adherent to CAN-SPAM and international equivalents. 

 
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g)   Photographs and frames in video recordings will only contain as far as possible the lower extremities of 
subjects and any ambulatory assistance provided with their hands only.  Frames containing the face or other 
identifiable features of subjects  will  be  blurred, cropped  or  deleted  if  accidentally  captured.  The data of 
subjects that are withdrawn  from  participation  will  be  retained.  Subjects may request that  their  research  
data  is  delinked  from  their  personally  identifiable data during the course of the study.   
h) In case of EDS, database entry is locked after final patient data is entered. Database is closed and de-
identified data exported by the sponsor Co-investigator/Monitor on completion of close-out monitoring activities 
including resolution of all data queries. Smart Trial audit history is extracted for records of monitoring activities. 
Exported de-identified data is stored on password protected PC intranet for analysis. In case of paper based data 
collection, de-identified data is scanned and shared with the sponsor Co-investigator/Monitor after data collection 
is complete. 
Representatives of the sponsor, sponsor co-investigators and monitors, will be present at the study sites. A 
declaration of confidentiality to be signed by the representatives, ensures necessary data protection. Sponsor 
representatives will only observe and not interact with subject during the investigational procedures. 
i) The data retention period for unlinked clinical data will be a minimum of 5 years in accordance with ISO 
14155:2020. Clinical investigation documents, including but not limited to CIP, CIB, CRFs and clinical 
investigation report(s) should be incorporated into the device technical documentation under the quality 
management system of the manufacturer. 
k)  A Clinical Investigation Report (CIR) will be generated by Össur Medical Office. The report will be stored with 
the device technical file within Össur Quality Management System, along with the unlinked data and all 
accompanying investigational documents, according to the R&D and Quality documentation procedures. 
Subjects participating in the study can have access to the results, on demand, when the CIR is internally 
published.  
Study results, data, and documentation will be stored for a minimum of 5 years.  
 
 

 
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20. Hafner, B. J. et al. Construct Validity of the Prosthetic Limb Users Survey of Mobility (PLUS-M) in Adults With 
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17 Annex