Multinational Randomized Controlled Cross-over Trial Comparing C -Brace to Conventional Knee Ankle Foot Orthoses With Respect to Balance, Fall Risk and Activities of Daily Living
Phase: NA
Conditions: Pareses, Lower Extremity
Sponsor: Otto Bock Healthcare Products GmbH

Protocol Title: 
Multinational randomized controlled cross-over trial 
comparing C-Brace to conventional knee ankle foot 
orthoses with respect to balance, fall risk and activities of 
daily living. 
NCT Number: 
NCT03906656 
Document Date 
(version 7):   
July 16, 2021 
 

 
CLINICAL  
INVESTIGATION PLAN 
Document 
number: 
PD-PS00120016A-
001 
Version  
number: 
7 
Project name 
Clinical trial comparing C-Brace to 
KAFO/SCO 
Project no. 
PS00120016A 
 
Otto Bock 
Confidential 
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Clinical Investigation Plan (CIP) 
 
Multinational randomized controlled cross-over trial comparing C-
Brace to conventional knee ankle foot orthoses with respect to bal-
ance, fall risk and activities of daily living. 
 
CONFIDENTIAL DOCUMENT 
Document No. PS00120016A-001 
 
REVISION RECORD 
Vers. No. 
Description 
Valid from 
1.0 
Creation of the clinical investigation plan 
Signed release 
2.0 
Changes include minor changes to inclusion/exclusion crite-
ria, addition of a second baseline to the study schedule, addi-
tion of US study sites, and other minor change for clarity. 
Signed release 
3.0 
Changes include changes to the statistical analysis descrip-
tion and other minor changes for clarity 
Signed release 
4.0 
Changes to address risks and effects of the COVID-19 pan-
demic including updated study timeline, adaptations to the 
study procedure (7.3.12), updated study flow chart (7.4), 
updated risk-benefit assessment (11), and COVID-19 Risk 
Factors Assessment and patient re-consent (17.3). 
Signed release 
5.0 
Inclusion of Austria as new participating country, updated 
study flowchart  
Signed release 
Prepared by 
Name / Function 
 
Dr. Marten Jakob 
Director Clinical Research and 
Services Duderstadt 
Date 
 
See digital signature 
Signature 
 
 
 
 
Approved 
and released 
by 
Name / Function 
 
Dr. Andreas Hahn 
Corporate Vice President Clinical 
Research and Services 
Date 
 
See digital signature 
Signature 
 
 
 

 
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Clinical trial comparing C-Brace to 
KAFO/SCO 
Project no. 
PS00120016A 
 
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REVISION RECORD 
Vers. No. 
Description 
Valid from 
6.0 
Changes to the statistical analysis and other minor changes 
for clarity. Moved primary safety endpoint to a secondary 
endpoint. Removed adaptive study design and amended 
planned interim analysis. 
Signed release 
7.0 
Updated enrollment number to account for screen failures 
and to reflect expansion to allow additional enrollments. 
Signed release 
 
Sponsor 
 
 
 
Otto Bock Healthcare Products GmbH  
Brehmstrasse 16 
1110 Wien 
 
Clinical Project Manager 
Dr. Marten Jakob 
Director Clinical Research and Services  
Ottobock SE & Co. KGaA 
Max-Näder Straße 15 
37115 Duderstadt 
Deutschland 
marten.jakob@ottobock.com 
 
 
Coordinating Investigator  
Prof. Dr. med. Frank Braatz  
Professor for Orthobionic  
Facharzt für Orthopädie und Unfallchirurgie, Physikalische und Rehabilitative Medizin  
Zentrum für Healthcare Technology der Privaten Hochschule Göttingen  
Weender Landstraße 3-7  
37073 Göttingen  
Deutschland 
 
Investigational Site 1  
Zentrum für Healthcare Technology der Privaten Hochschule Göttingen  
Weender Landstraße 3-7  
37073 Göttingen  
Deutschland 
 
Principal Investigator  
 
Prof. Dr. med. Frank Braatz  
Professor for Orthobionic  

 
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Facharzt für Orthopädie und Unfallchirurgie, Physikalische und Rehabilitative Medizin  
 
 
 
Investigational Site 2 
Katholisches Klinikum Koblenz-Montabaur 
Kardinal-Krementz-Str. 1-5 
56073 Koblenz 
 
Principal Investigator 
Dr. med. Axel Ruetz 
Facharzt für Orthopädie und Unfallchirurgie 
 
Investigational Site 3 
Adelante Kenniscentrum 
Zandbergsweg 111 
6432 CC Hoensbroek 
 
Principal Investigator 
Dr. Bea Hemmen 
Rehabilitation specialist 
 
Investigational Site 4 
Universitätsklinikum Heidelberg 
Zentrum für Orthopädie, Unfallchirurgie und Paraplegiologie 
Schlierbacher Landstraße 200a 
69118 Heidelberg  
 
Principal Investigator 
PD Dr. Rüdiger Rupp 
 
Investigational Site 5 
Scheck & Siress 
2835 N Sheffield, Ste 301 
Chicago, IL 60657 
 
Principal Investigator 
Jason Wening, CPO, FAAOP 
 
Investigational Site 6 
Hanger Clinic 
11155 South Main Street 
Houston, TX 77025 
 

 
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Project no. 
PS00120016A 
 
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Principal Investigator 
Tom DiBello, LO, CO, FAAOP 
Investigational Site 7 
Hanger Clinic Florida 
5432 Bee Ridge Road 
Sarasota, FL 34233 
 
Principal Investigator 
Chris Toelle, LCO, ACM 
 
Investigational Site 8 
Hanger Clinic 
4518 51st. Ave SW 
Seattle, WA 98116 
 
Principal Investigator 
Eric Weber, LCPO, FAAOP 
 
Investigational Site 9 
Orthopädisches Spital Speising 
Speisingerstraße 109 
AT-1130 Wien 
 
Principal Investigator 
Dr. Alexander Krebs 
 
 

 
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Project no. 
PS00120016A 
 
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Signature sheet 
 
 
Sponsor 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Andreas Hahn 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Marten Jakob 
 
 
 
Coordinating Investigator (if multicenter) 
 
 
 
 
______________________________________________________________ 
Place, Date, 
Prof. Frank Braatz 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator Site 1 

 
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Project no. 
PS00120016A 
 
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______________________________________________________________ 
Place, Date,  
Prof. Frank Braatz 
 
 
Investigator / Co-investigator Site 1 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Jennifer Ernst 
 
 
Investigator / Co-investigator Site 1 
 
 
 
______________________________________________________________ 
Place, Date,  
Heiko Drewitz 
 
 

 
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Project no. 
PS00120016A 
 
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Principal Investigator Site 2 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Axel Ruetz 
 
 
Investigator / Co-investigator Site 2 
 
 
 
______________________________________________________________ 
Place, Date,  
Randolf Comtesse 
 
 

 
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Project no. 
PS00120016A 
 
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Principal Investigator Site 3 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Bea Hemmen 
 
 
Investigator / Co-investigator Site 3 
 
 
 
______________________________________________________________ 
Place, Date, Signature  
 
 

 
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Project no. 
PS00120016A 
 
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Principal Investigator Site 4 
 
 
 
______________________________________________________________ 
Place, Date,  
PD Dr. Rüdiger Rupp 
 
 
 
 
 
Investigator / Co-investigator Site 4 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Cornelia Hensel  
 
 
 
 
 
Investigator / Co-investigator Site 4 
 
 
 
______________________________________________________________ 
Place, Date,  
Dr. Steffen Franz  
 

 
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Principal Investigator Site 5 
 
 
 
______________________________________________________________ 
Place, Date,  
Jason Wening 
 
 
Investigator / Co-investigator Site 5 
 
 
 
______________________________________________________________ 
Place, Date,  
Signature 

 
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Principal Investigator Site 6 
 
 
 
______________________________________________________________ 
Place, Date,  
Tom DiBello 
 
 
Investigator / Co-investigator Site 6 
 
 
 
______________________________________________________________ 
Place, Date, Signature  
 
 
 
 

 
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Principal Investigator Site 7 
 
 
 
______________________________________________________________ 
Place, Date,  
Chris Toelle 
 
 
Investigator / Co-investigator Site 7 
 
 
 
______________________________________________________________ 
Place, Date, Signature  
 

 
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Principal Investigator Site 8 
 
 
 
______________________________________________________________ 
Place, Date,  
Eric Weber 
 
 
Investigator / Co-investigator Site 8 
 
 
 
______________________________________________________________ 
Place, Date, Signature  
 

 
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Principal Investigator Site 9 
 
 
 
______________________________________________________________ 
Place, Date,  
 
Dr. Alexander Krebs 
 
 
Investigator / Co-investigator Site 9 
 
 
 
______________________________________________________________ 
Place, Date,  
 
Dr. Andreas Kranzl 
 

 
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 Table of Contents 
 
1 
Study Overview 
18 
2 
Abbreviations 
22 
3 
Background 
23 
4 
Rationale 
25 
5 
Investigational Device Information 
25 
5.1 
Manufacturer 
25 
5.2 
Description of the investigational device 
26 
5.2.1 
Technical description of mpKnee joint 
28 
5.3 
Necessary training and experience to use the investigational 
30 
device (C-Brace) 
30 
5.3.1 
Orthopaedic technician 
30 
5.3.2 
Patient 
30 
5.4 
Comparator Devices 
31 
5.5 
Accommodation to the devices 
31 
5.6 
Specific medical or surgical procedure involved 
31 
5.7 
Receipt, distribution and usage 
31 
6 
Study objectives and hypotheses 
31 
6.1 
Objectives 
31 
6.1.1 
Primary objective 
31 
6.1.2 
Secondary objectives 
32 
6.1.3 
Endpoints 
32 
6.2 
Hypothesis 
32 
7 
Study design 
33 
7.1 
Experimental plan 
33 
7.2 
Measures taken to minimize bias 
33 
7.3 
Study visits and procedures 
33 
7.3.1 
Patient enrollment 
33 
7.3.2 
Screening and baseline procedures 
34 
7.3.3 
Randomization 
35 
7.3.4 
Fitting and Accommodation 
36 
7.3.5 
Home use (both arms) / Follow-up phone calls 
37 
7.3.6 
Study visit 1 
37 
7.3.7 
Cross –over process 
39 
7.3.8 
Wash out phase 
39 
7.3.9 
Study visit 2 
39 
7.3.10 Patient´s C-Brace use after study end 
39 
7.3.11 Transfer of patients to C-Brace registry for long term follow up 
39 
7.3.12 Adaptations to the study procedure due to the COVID-19 pandemic 
40 
8 
Outcomes measures 
42 
8.1 
General data collection 
42 
8.2 
Outcome measures 
42 
8.2.1 
Primary study objective 
42 

 
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8.2.2 
Secondary study objectives 
43 
8.3 
Study schedule 
50 
9 
Patient population 
51 
9.1 
Number of patients to enroll 
51 
9.2 
Duration individual patient’s participation 
51 
9.3 
Inclusion and Exclusion Criteria: 
51 
9.3.1 
Inclusion criteria 
51 
9.3.2 
Exclusion criteria 
52 
9.3.3 
Drop out or early termination of the study 
53 
10 Statistics 
53 
10.1 Sample size calculation 
53 
10.1.1 Primary efficacy endpoint 
54 
10.1.2 Secondary endpoints 
54 
10.2 Management of missing, unused or spurious data 
55 
10.3 Planned statistical analysis 
56 
10.3.1 General patient and orthosis use data 
57 
10.3.2 Primary efficacy outcome 
57 
10.3.1 Secondary outcome analysis 
58 
10.3.2 Randomization procedure 
58 
10.4 Interim analysis 
58 
11 Risk and benefit of the investigation device and clinical investigation 
60 
12 Management of adverse events 
63 
12.1 Description of possible adverse events & adverse device effects 
63 
12.2 Definitions 
63 
12.2.1 Additional national definitions 
64 
12.3 Documentation of Adverse Events / Serious Adverse Events 
65 
12.4 Reporting of Adverse Events / Adverse Device Effects 
65 
12.4.1 Additional national requirements for reporting of adverse events 
66 
13 Monitoring 
68 
13.1 Direct Access to Source Data/Documents 
68 
13.2 Source Documents and Source Data 
69 
14 Data management 
69 
15 Documentation and administration 
70 
15.1 Investigator’s Brochure 
70 
15.2 Deviations from Clinical Study Protocol 
70 
15.3 Amendments to the Clinical Study Protocol 
71 
15.4 Final Report 
72 
16 Study Discontinuation 
72 
16.1 Investigational Site Termination 
72 
16.2 Premature discontinuation of the complete study 
72 
16.3 Requirements for patient follow up 
73 
17 Ethical considerations 
73 
17.1 Independent ethics committee 
73 
17.2 Ethical conduct of the study 
73 
17.3 Patient information and informed consent 
74 

 
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17.4 Patient insurance 
75 
18 Disclosure of data and publication policy 
76 
19 Retention of records 
76 
20 Study timeline 
77 
21 Publication Plan 
77 
22 References 
78 
23 Appendix 
79 
23.1 Appendix I: Procedure for device read-outs 
79 
23.2 Appendix II: Study Overview (German) 
82 
23.3 Appendix III: Example of the phone call protocol 
87 
 
 

 
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1 Study Overview 
Sponsor 
Otto Bock Healthcare Products GmbH 
Short Study Title 
 
Clinical trial comparing C-Brace to KAFO/SCO 
Objective 
To evaluate effectiveness and benefits in patients with lower 
limb impairment in activities of daily living comparing the C-
Brace microprocessor – controlled stance and swing orthosis to 
standard of care use of knee ankle foot orthosis/stance control 
orthoses 
Design 
Prospective international multicenter open-labeled randomized 
controlled cross-over trial 
Devices 
C-Brace, KAFOs, SCOs 
Primary Efficacy End-
point 
Improvement of static and dynamic balance by using C-Brace 
compared to KAFO /SCO  
Secondary Endpoints 
1. To evaluate the effect of the C-Brace compared to KAFO/SCO 
on gait, balance, plain level walking, walking during more 
challenging tasks and divided attention tasks during walk-
ing.  
2. To assess and compare the safe use of the C-Brace compared 
to KAFO/SCO in regards to falls: frequency of falls, severity 
of falls, fall-related injuries, fear of falling  and related 
treatment efforts.  
3. Evaluation of patient`s confidence in performing various 
ambulatory activities without falling using C-Brace com-
pared to KAFO/SCO. 
4. Assessment of quality of life and re-integration to normal 
living using C-Brace compared to KAFO/SCO. 
5. Assessment of disability and impact on productivity. 
6. Assessment of patient´s C-Brace satisfaction and usage hab-
its compared to KAFO/SCO 
7. Reduced probability of falling more than once by using C-
Brace compared to KAFO / SCO  

 
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Clinical Follow-up 
Screening, 2 baselines, visit 1 after 3 months usage of device 1 
at home, visit 2 after 3 months usage of device 2 at home 
No of patients 
At least 56 randomized 
Inclusion criteria 
• Patient has been tested with the Trial Tool (DTO) and 
demonstrated the potential to utilize the C-Brace suc-
cessfully 
• Patient has a BBS score < 45 
• Lower limb functional impairment according to CE label 
wording 
• Prior active and compliant use of unilateral or bilateral 
KAFO or SCO in the past 3 months prior to enrollment in 
the study 
• Patient meets minimum physical requirements to be fit-
ted with a C-Brace, such as muscle status, joint mobility, 
leg axis and proper control of the orthosis must be guar-
anteed. 
• The User must fulfill the physical and mental require-
ments for perceiving optical/acoustic signals and/or me-
chanical vibrations 
• The existing muscle strength of the hip extensors and 
flexors must permit the controlled swing-through of the 
limb (compensation using the hip is possible). 
• Patient´s commitment to use C-Brace 2 at least 1-2  
hours per day 5 days per week- 
• Patient is ≥ 18 years old 
• Patient is willing and able to independently provide in-
formed consent. 
• Person is willing to comply with study procedures 
Exclusion criteria 
• Patient who is not able to follow the entire study visits or 
is unwilling/unable to follow the instructions 
• Patient was not able to use DTO 
• Patient who is not using an orthosis at least 1 to 2 hours/ 

 
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day for 5 days per week 
• Patient with body weight > 125 kg (includes body weight 
and heaviest object (weight) carried) 
• Patient with Orthoprosthesis 
• Patient with flexion contracture in the knee and/or hip 
joint in excess of 10° 
• Patient with uncontrolled moderate to severe spasticity 
(relative contraindication moderate spasticity) 
• Leg length discrepancy in excess of 15 cm 
• Patient with unstable neurological or cardiovascu-
lar/pulmonary disease, cancer 
• Pregnancy 
• Patient using a C-Brace 
• Patient with known vertigo or with history of falls unre-
lated to orthosis use or unrelated to motor disability 
• Patient who has never been fitted an orthosis before 
• Patient is not able to answer the self-administered ques-
tionnaires independently; for patients with upper ex-
tremity impairment is it allowed to verbally answer the 
questions. 
• Patient participating already in a study during this 
study´s duration 
• Patient participated in earlier C-Brace studies 
Estimated Time Course 
Estimated study duration: 
First Patient In: 1 Mar 2019 
 
Last Patient In: 31 Dec 2021  
Last Patient Out: 31 Mar 2023  
Principal Investigators 
Site 1: Prof. Frank Braatz 
Site 2: Dr. Axel Ruetz  
Site 3: Dr. Bea Hemmen 
Site 4: PD Dr. Rüdiger Rupp 

 
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Site 5: Jason Wening, CPO, FAAOP  
Site 6: Tom DiBello, LO, CO, FAAOP 
Site 7: Chris Toelle, LCO, ACM  
Site 8: Eric Weber, LCPO, FAAOP 
Site 9: Dr. Alexander Krebs 
Clinical Site Locations 
Site 1: Göttingen (D) 
Site 2: Koblenz (D) 
Site 3: Hoensbroek (NL) 
Site 4: Heidelberg (D) 
Site 5: Chicago, IL (USA) 
Site 6:  Houston, TX (USA) 
Site 7: Sarasota, FL (USA) 
Site 8: Seattle, WA (USA) 
Site 9: Wien (AT) 
Clinical Project Manager  Dr. Marten Jakob 
 
 

 
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2 Abbreviations 
AE 
Adverse Event 
ABC 
Activities-specific balance confidence scale 
ADE 
Adverse Device Effect 
BBS 
Berg Balance Scale 
C-Brace 
Axon Orthotic System 
CRF 
Case Report Form 
CB2 
C-Brace 2 (the New C-Brace) 
CIP 
Clinical Investigation Plan = Protocol 
CPO 
Certified Prosthetist/Orthotist 
DGI 
Dynamic Gait Index 
DTO 
Trial tool (Diagnostische Testorthese) 
EC 
Ethics Committee 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
KAFO 
Knee Ankle Foot Orthoses 
PRO 
Patient reported outcome 
OPUS 
Orthotic and Prosthetic User Survey 
QUEST 
Quebec User Evaluation of Satisfaction with Assistive Technology 
RNL 
Re-integration to normal living 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SAI 
Stair Assessment Index 
SCO 
Stance Control Orthoses 
SF-36 
Medical Outcome Study Short Form 
tbd 
To be defined 
WLQ 
Work limitations questionnaires 
US 
United States 
6MWT 
6-Minute Walk Test 
 
 
 

 
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3 Background 
 
The estimated incidence for people with lower limb weakness due to neurologic, neu-
romuscular or orthopedic impairment, such as lower motor neuron injury, spinal cord 
injury, multiple sclerosis, post-polio syndrome, stroke, arthritis or trauma requiring the 
use of an orthosis for walking is about 394.400 cases in Germany (1). It is estimated 
that approximately 0.01 % of those requiring an orthosis will benefit from a C-Brace. 
Distribution is comparable in other countries like the US.  
People with lower limb weakness due to neurologic, neuromuscular or orthopedic im-
pairment, such as lower motor neuron injury, spinal cord injury, multiple sclerosis, 
post-polio syndrome, stroke, arthritis or trauma may require the use of a knee-ankle-
foot orthoses (KAFO) for walking. The conventional KAFO has a knee joint that can be 
“locked” in extension during ambulation, but this can cause abnormal gait patterns 
with hip hiking, circumduction and vaulting during walking (2). These gait deviations 
using conventional KAFOs may contribute to chronic pain, decreased mobility and a 
higher physiological energy cost (2,3)  
Stance Control Orthoses (SCO) are usually knee ankle foot orthoses (KAFO) that have a 
built-in locking mechanism which locks the knee joint for the stance phase and unlocks 
it for the swing phase of gait. The stance-control knee-ankle-foot orthosis (SCO) has 
addressed some of these issues by mechanically locking the orthotic knee joint during 
the stance phase of gait while allowing free knee flexion during swing. 
 
These devices have been shown to improve gait kinematics and gait speed on level 
ground in compared to the use of KAFOs (2,4). Due to the method needed to engage the 
knee lock for stance, however, users have reported increased mental effort to use these 
devices, specifically to disengage the knee for initiation of swing (5). Success in using 
SCOs has been limited by balancing the need to resist flexion in stance and providing a 
lightweight and small device. The challenges that remain for the SCO are to control the 
knee in flexion, missing knee flexion under load and extension phases and to switch 
smoothly between the phases (6). 
Current evidence finds that the benefit of KAFO use is for home mobility, general exer-
cise and standing (7) and that, in general, most patients feel that the difficulties and 
inconvenience encountered with the orthoses and the modest increase in function do 
not warrant their acceptance for regular, daily use in functional activities (7).  However, 
walking provides exercise to promote musculoskeletal and mental health benefits to 
counteract the effects of long-term wheelchair use. It may also increase functional in-
dependence, community participation and re-integration back to normal life and work. 

 
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On the other hand, there is low knowledge about disability and the impact on work 
background as well as re-integration into work. 
A KAFO orthotic device that can provide mechanical support while allowing greater 
control in swing and stance phases of gait may increase the user’s ability to walk with 
decreased metabolic cost and mental effort to allow increase functional mobility and 
participation in daily activities allowing a self-administered life. 
The C-Brace orthotic system is designed with custom thigh and calf shells connected by 
a monocentric knee joint with a microprocessor-controlled linear hydraulic damper. 
The orthotic knee is equipped with a sensor that detects the knee angle and knee angle 
velocity. The microprocessor controls extension and flexion dampening of the hydrau-
lic knee joint separately by adjusting two valves with the help of servomotors and a 
planetary gear set. In this way, the entire gait cycle is controlled in real time. The C-
Brace is a default-stance orthosis that switches into low flexion resistance for swing 
when a pre-set, customizable ankle moment is exceeded, while the knee is simultane-
ously extended, followed by significant knee flexion. It switches back to high flexion 
resistance for stance as early at the initiation of knee extension.  The C-Brace offers con-
trolled stance knee flexion, knee flexion during weight-bearing and dynamic control of 
the swing phase. Knee flexion during weight bearing makes it possible to reciprocally 
descend ramps and stairs and to sit down with both legs loaded. We hypothesize that 
the use of C Brace in comparison to conventional KAFO / SCO systems shall lead to a 
better balance associated with a reduced risk of falling, hence allowing better participa-
tion and an increase in quality of life. 
 
C-Brace Clinical data  
 
Title 
Objective(s) 
Comparator(s) 
Patient 
number  
Published 
Prospective, pilot 
study to evaluate per-
formance, patient ben-
efits and acceptance of 
a new generation of C-
Brace microprocessor-
controlled stance and 
swing control ortho-
sis– AOS 
Safety and func-
tionality of CB2 
KAFO/SCO 
8 
Study final 
Dec 2018 
Clinical Algorithm for 
Post-Stroke Gait Train-
ing with C-Brace 
functionality 
N/A 
15 
recruiting 
Micro-processor con-
trolled Knee-Ankle-
Metabolic, func-
tionality, safety 
SCO 
18 
Study final, 
publication 

 
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Foot Orthosis (C-Brace) 
vs. Stance-control 
Knee-Ankle-Foot Or-
thosis (SCO) and con-
ventional Knee-Ankle-
Foot Orthosis (KAFO): 
Functional Outcomes 
in Individuals with 
Lower Extremity Im-
pairments due to Neu-
rologic or Neuromus-
cular Disease, Ortho-
pedic Disease or Trau-
ma (RIC) 
in prepara-
tion 
A Prospective Registry 
of patients fitted with a 
microprocessor-
controlled knee ankle 
foot orthosis 
Functionality, 
safety 
KAFO/SCO 
150 
recruiting 
Table 1: Published and non-published clinical data on C-Brace 
 
4 Rationale 
The C-Brace microprocessor (MP) controlled hydraulic system is the next generation in 
the development of lower limb orthoses allowing more control during the swing and 
stance phases of gait. The device will provide better static and dynamic balance leading 
to a reduced risk of falling.  Improvements may comprise stand to sit transfers, walking 
on uneven surfaces, slopes and stairs. Such functions may help to improve patients´ 
mobility, integration, participation and quality of life. 
The study will specifically evaluate the potential of the C-Brace to improve the efficacy 
in daily life activities and benefits for individuals with lower extremity functional im-
pairments as compared to SCOs and conventional KAFOs.  
 
5 Investigational Device Information 
Intervention: C-Brace  
5.1 Manufacturer 
Otto Bock Healthcare Products GmbH 
Brehmstraße 16,  
1110 Vienna 

 
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Austria  
 
Version investigational device 
Model number: 
17KO1=* 
Device name: 17KO1 C-Brace Gelenkeinheit / C-Brace joint unit  
Investigational device comprises: 
- 
Microprocessor controlled knee joint (model no. 17KO1) 
- 
Custom made orthotic shells for each patient 
 
C-Brace is a class I device according to 93/42/EEC Annex IX and according to Regula-
tion (EU) 2017/745 Annex VIII 
CE-mark was obtained 14 Jun 2018. 
 
For further technical details about the product, product development and testing pro-
cedures please refer to the Investigator’s brochure (IB). 
5.2 Description of the investigational device 
Intended use  
The C-Brace microprocessor swing and stance control orthosis is used for patients with 
paresis or flaccid paralysis of the lower limbs (e.g. due to post-polio syndrome, trau-
matic paresis including paraplegia) requiring orthotic knee support. 
 
Indications / Contraindications C-Brace 
Suitable patients will fulfil the following criteria: 
 
- 
Unilateral or bilateral lower limb paresis or flaccid paralysis e.g. due to post-
polio syndrome, traumatic paresis including paraplegia. 
- 
Physical prerequisites such as muscle status, joint mobility and possible axis 
deviations are crucial and proper control of the orthosis must be guaranteed. 
- 
The user must fulfill the physical and mental requirements for perceiving opti-
cal/acoustic signals and/or mechanical vibrations 
- 
The existing muscle strength of the hip extensors and flexors must permit the 
controlled swing through of the limb (compensation using the hip is possible). 
 
Patients will not be suitable for using the system if they show the following: 
Absolute contraindications: 
- 
Flexion contracture in the knee and/or hip joint in excess of 10° 
- 
Knee varus/valgus malposition in excess of 10° 
- 
Severe spasticity 

 
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- 
Body weight over 125 kg / 275 IBs 
Relative Contraindications 
- 
Moderate spasticity 
 
Technical description of the C-Brace 
The C-Brace consists of individually manufactured orthotic shells, which interface with 
the thigh, shank and foot. The orthotic shells are made out of commonly used materials 
in orthotics. 
The knee joint is controlled by a microprocessor controlled joint unit, while the ankle 
joint is designed according to the patient’s needs. Elastic elements (such as the C-Brace 
carbon fiber spring) or state of the art orthotic joints can be used. 
 
Figure 1 C-Brace existing of thigh, tibial and foot shell, mpKnee joint and medial follower. 
 
Knee joint motion is controlled using a microprocessor-controlled joint (mpKnee joint) 
which consists of microprocessor-controlled hydraulic cylinders that can provide vari-
able resistance. The microprocessor uses the signals from various sensors to adjust the 
joint behavior in real-time, according to situation (i.e. phase in gait cycle). For example, 
during stance phase of gait the knee joint provides high resistance to stabilize the pa-
tient. During swing phase, the knee joint switches to minimum resistance and is almost 
free (only inner friction of the system). At maximum resistance, joint motion is blocked. 
The joints are capable of providing any resistance between these extreme points. For 
further technical details about the mpKnee joint unit, please refer to chapter 5.2.1 
Technical description of mpKnee Joint. 
 
The patient has the possibility to turn the system on and off via a control panel. Fur-
thermore, the patient gets information on the control panel about the battery status, if 
service is required (after a certain amount of cycles or if a problem with the sensor is 

 
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detected by the system) and about the Bluetooth status (see Figure 2: Control panel of C-
Brace). Bluetooth can be initialized by the patient if he/she wants to use the Remote 
Control App. The App will be comparable to the one available for Ottobock’s micropro-
cessor controlled prosthetic knee and foot prostheses Genium, C-Leg and Meridium. 
The use and application of the control panel as well as the Remote Control App is de-
scribed more detailed in the instruction for use.  
 
 
Figure 2: Control panel of C-Brace 
 
5.2.1 Technical description of mpKnee joint 
The knee joint for the Braces used in this study as shown in “Figure 3: Microprocessor 
controlled knee joint unit” is controlled by microprocessor controlled hydraulics. The 
knee joint can only dissipate energy and is not capable of energy storage. As the hy-
draulic unit has two valves, flexion and extension resistance can be controlled inde-
pendently. This means that flexion resistance can be high but at the same time exten-
sion resistance can be low, which is a safety feature.  
The unit has a modular design with electronic components connected with the proprie-
tary AXON bus, with the exception of the hydraulic sensor. 
 
The system control is based on signals from several sensors:  
• 3D accelerometers and gyroscopes measure motion and orientation in space. 
• A hydraulic force sensor measures the load that is transmitted by the Brace sys-
tem. 

 
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• Knee angle is measured with a special sensor based on magnetic principles. 
 
 
 
 
Figure 3: Microprocessor controlled knee joint unit 
 
The control paradigm is mainly based on the evaluation of motion signals. Thus, it can 
provide optimum support in every phase of the gait cycle. In level walking, the system 
would behave in the different gait phases according to the following table: 
 
Gait phase 
Knee joint resistance 
Effect on gait. 
Heel strike 
High flexion 
Low extension 
Stance phase stability, stance phase flexion 
is possible 
Mid stance 
(rollover) 
High flexion 
Controlled extension 
Stance phase stability 
Stance phase extension controlled for soft 
extension stop and improved propulsion 
Toe off 
Low flexion 
Low extension 
Swing initiation, knee can bend 
Extension is free.  
Swing 
phase flex-
Controlled flexion 
Low extension 
Knee flexion angle can be controlled to 
achieve a physiological knee angle 

 
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ion 
Extension is free. 
Swing 
phase ex-
tension 
High flexion 
Low extension 
Flexion resistance is high to provide support 
in case of stumbling. 
Extension is free. 
Terminal 
swing 
High flexion 
Controlled extension 
Flexion resistance is high to provide support 
in case of stumbling. 
Extension is controlled for soft extension 
stop.  
Table 1: Description of the knee joint resistance depending on the gait phase and the respective effect on gait.  
The system only activates swing initiation at toe off if a signal pattern that is typical for 
level walking is detected. 
The control system is kept as simple as possible; it is principally based on posture con-
trol. This method has proven to be appropriate for the control of prosthetic knee joints 
(e.g. C-Leg 4). For safety reasons also load signals representing the knee moment are 
taken into account. Therefore, the knee joint does not switch to a low flexion resistance 
for swing initiation if a flexion moment is measured. Such “default stance” behavior of 
the system is inherently safe. 
 
 
5.3 Necessary training and experience to use the investigational 
device (C-Brace) 
5.3.1 Orthopedic technician 
The orthopedic technician needs a C-Brace (C-Brace 2) certification. 
5.3.2 Patient 
The patient will be trained to put on C-Brace, to use the cockpit app and perform ad-
justments safe and routinely. Training will be performed by a certified CPO or physio-
therapist.  
 
Patient will be discharged with C-Brace only if he/she demonstrated that he/she was 
able to walk safely and is able to program the device. This will be assessed with a 
benchmark system within the adaption phase (see section 7.3.4). 
 

 
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5.4 Comparator Devices 
The C-Brace will be compared with the standard SCOs or KAFOs, which have been pre-
scribed in clinical routine to the patient. All CE registered SCOs or KAFOs are allowed. 
 
5.5 Accommodation to the devices 
During the phase of system setup, patients will receive appropriate accommodation 
support.  
For details of accommodation support, please see section 7.3.4.  
 
5.6 Specific medical or surgical procedure involved 
Not applicable. 
 
5.7 Receipt, distribution and usage 
During screening, the site will test the patients regarding the ability to use C-Brace. 
During this testing procedure, the parameters will be documented and sent to Ottobock 
afterwards.  
Final assembly of the patient-specific C-Brace orthosis will be performed either at Ot-
tobock SE & Co. KGaA in Duderstadt, Germany or at the study site. In case, Ottobock is 
responsible for assembly, Ottobock will provide the study site with the assembled C-
Brace orthoses. All orthoses will be labeled with a specific label “For clinical investiga-
tion only”. Shipment of the final assembled orthosis is done by Ottobock Duderstadt. In 
case assembly is done at the study site, Ottobock Duderstadt will provide the study site 
with sufficient mpKnee joints. The mpKnee joints will be labeled “For clinical investiga-
tion only”. Traceability of all investigational devices is ensured by maintaining a device 
accountability log.  
If study patients decide not to keep C-Brace for up to 24months after finishing the 
study, C-Brace needs to be sent back to Ottobock Duderstadt.  
6 Study objectives and hypotheses 
6.1 Objectives  
6.1.1 Primary objective 
Primary Efficacy Endpoint 

 
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Improvement of static and dynamic balance by using C-Brace compared to KAFO/SCO. 
 
6.1.2 Secondary objectives 
• To evaluate the effect of the C-Brace compared to KAFO/SCO on gait, balance, 
plain level walking, walking during more challenging tasks and divided atten-
tion tasks during walking.  
• To assess and compare the safe use of the C-Brace compared to KAFO/SCO in re-
gard to falls: frequency of falls, severity of falls, fall-related injuries, fear of fall-
ing and related treatment efforts.  
• Evaluation of patient`s confidence in performing various ambulatory activities 
without falling using C-Brace compared to KAFO/SCO. 
• Assessment of quality of life and re-integration to normal living using C-Brace 
compared to KAFO/SCO. 
• Assessment of disability and impact on productivity. 
• Assessment of patient´s C-Brace satisfaction and usage habits compared to 
KAFO/SCO.  
• Reduced probability of falling more than once by using C-Brace compared to 
KAFO / SCO 
6.1.3 Endpoints 
Assessments will be taken at baseline with the patient’s own orthotic device, after 
completing the first randomization phase and after completing the second randomiza-
tion phase. Please refer to section 8 Outcome Measures. 
 
6.2 Hypothesis  
The primary hypothesis is that the microprocessor based C-Brace technology will help 
moderately active patients to improve balance compared to a non-microprocessor con-
trolled KAFO/SCO. 
As a consequence, the C-Brace should help reduce the risk of falling/falls in these pa-
tients and eventually make them more independent in their daily life activities includ-
ing their job and improve their quality of life, which represents the secondary hypothe-
sis of the is study. 
 

 
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7 Study design  
This is a prospective international multicenter randomized controlled cross-over open-
labeled trial. 
The study will have multiple sites in the United States, Germany, Netherlands and Aus-
tria. In total 56 patients will be recruited. Patients can be enrolled in a competitive 
manner without any allocation.  
 
7.1 Experimental plan  
After obtaining informed consent, patients will be screened. Patients fulfilling inclu-
sion/exclusion criteria will be enrolled in the study. After screening, a first baseline 
assessment will be conducted. Within maximum 48 hours, a second set of baseline da-
ta will be collected. Afterwards the participants will be randomly assigned to be fitted 
either with C-Brace or maintain his/her KAFO/SCO. The randomization procedure will 
be concealed and assigned off-site. After fitting, an accommodation period follows that 
will last up to 14 days prior home use. The first follow-up data collection will occur af-
ter 3 months after the initial home use period. Afterwards, the patients will cross over 
to KAFO/SCO or C-Brace, respectively. The participants who were fitted with C-Brace 
will cross over to KAFO/SCO and vice versa. Another accommodation phase will be of-
fered for both C-Brace and KAFO/SCO wearers to ensure that the patient can properly 
use both devices before the cross-over home use period. The second follow-up data col-
lection will occur after 3-months of home use. At the end of the study, the patients can 
choose to keep C-Brace until reimbursement or return to their original KAFO/SCO.  
7.2 Measures taken to minimize bias  
The research center will delegate the role of assessor to one trained employee. The as-
sessor will be responsible for evaluating functionality of participants in the perfor-
mance-based tests in all phases of the study. During all performance tests, patients will 
be instructed to refrain from giving any comments. The certified prosthetist (CPO) and 
physical therapist cannot be blinded.  
7.3  Study visits and procedures 
7.3.1 Patient enrollment 
This study will enroll up to 150 eligible patients. At least 56 subjects passing screening 
will be randomized. Dropouts shall be replaced, a dropout rate of 20% is assumed. Re-
cruitment planning shall be done in accordance with the capabilities of the centers. 
Competitive recruitment shall be allowed. All means to increase recruitment shall be 
taken. 

 
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Treatment failures: C-Brace must be fitted according to Ottobock instructions. During 
study visits, the C-Brace fitting quality will be checked; poor fitting quality needs to be 
corrected and may be reported as adverse event (AE) or adverse device effect (ADE). For 
definitions, please refer to section 12.2.     
Patients who do not comply with using the C-Brace at least 1-2 hours per day 5 days per 
week will be included in the intention to treat analysis only; however, they will be ex-
cluded from the per-protocol analysis. 
Potential patients will be called by the participating sites and pre-screened for study 
eligibility. In addition, patients contacting the sites or visiting them on a routine basis 
can be also pre-screened. 
 
 
7.3.2 Screening and baseline procedures 
Pre-screening prior to informed consent may be done with chart reviews or following 
standard of care assessments to determine if subjects may be potential candidates for 
the study. Assessments performed exclusively to determine eligibility for this study 
would be done only after informed consent has been obtained.  
Assessments performed for clinical routine and documented in patient´s records may 
be used for baseline even if they have been done prior to informed consent being ob-
tained. 
A screening log will be tracked. Screening failures will be documented.  
If the patient enrollment and screening is done at a location separate from the orthotic 
clinic (e.g. rehabilitation clinic), remote screening including a video of the performance 
of the BBS will be done at the orthotic clinic to reduce patients’ travel efforts to the in-
vestigator. Patients must give their informed consent before entering this remote 
screening procedure. 
Two baseline assessments will be performed in order to generate a more confident 
baseline assessment. Both baseline assessments should be performed within 1 or 2 
days. Only the first baseline measurement will be used for statistical analysis.  
7.3.2.1 The screening procedures include: 
• Informed consent 
• Inclusion/Exclusion criteria 
• Ability of the patient to sufficiently use C-Brace (via DTO testing) 
• Berg Balance Scale  
• Demographics: age, gender, ethnicity, weight, height, BMI 

 
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• General health information 
• Functional muscle test (Janda) / Manual Muscle Testing (MMT) 
• Sensitivity test (Rydel-Seiffer Test)  
• Passive range of motion assessment (neutral zero method) 
• Medical history: Joint replacement, current orthosis use, current use of assistive 
devices, fall history  
7.3.2.2 The first baseline procedures include: 
• Review patient’s eligibility criteria 
• Functional and self-reported baseline assessment (Full assessment of outcome 
measures) 
 
 
Performance Assessment 
Functional assessment will be done using the Berg Balance Scale, the 6-minute walk 
test, Dynamic Gait Index, and the Stair Assessment Index. If the first baseline proce-
dure is performed within 24 hours of the screening, the results from the Berg Balance 
Scale testing, obtained during screening, may be used as first baseline value.  
Self – administered Questionnaires: 
Activity-specific Balance Confidence Scale, Reintegration to Normal Living index ques-
tionnaire, EQ-5D-5L, SF36, Work limitation questionnaire and the OPUS questionnaire. 
For a detailed description of administered questionnaires, please refer to section 8.2. 
Note that screening and first baseline procedures may be combined in one visit. 
For statistical analysis, only values from the first baseline will be used. Values from 
second baseline will be used only to support the values from the first baseline.  
7.3.2.3 The second baseline procedures include: 
• Functional baseline assessment (Performance assessment) 
7.3.2.4 C-Brace potential 
Testing C-Brace potential (DTO) with patients is done during screening to ensure the 
use is appropriate and possible. In the case, a patient cannot fulfill the test criteria; this 
will be handled as a screening failure.  
 
7.3.3 Randomization 
Patients are assigned to treatment groups by means of a state-of-the-art randomization 
procedure. For details on the randomization procedure, please refer to section 10.3.1.  

 
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7.3.4 Fitting and Accommodation 
7.3.4.1 KAFO / SCO 
Patients entering the study will use their existing fitted KAFO/SCO.  
Up to 10 hours of accommodation support with a physical therapist/orthotist will be 
provided in-house after enrollment within 2 weeks. The progress of accommodation 
will be assessed and documented. Benchmarks will be used to check patients’ ability to 
use their current orthosis. Two levels will be used for benchmarking: 
• Level 1, the minimum requirement for all patients to use their current device 
should be demonstrated at two different points in time (see 7.3.4.3). 
• Level 2 will be documented for patients with higher functional status, walking 
outdoors, over ground surfaces, steep ramps, slopes and climbing stairs with 
step-over-step pattern. 
 
7.3.4.2 C-Brace 
Up to 10 hours of accommodation support with a physical therapist/orthotist will be 
provided in-house after definitive fitting within 2 weeks. The progress of accommoda-
tion will be assessed and documented. Benchmarks will be used to check patient’s 
readiness to be discharged with C-Brace.  
• Level 1, the minimum requirement for all patients to use C-Brace should be 
demonstrated at two different points in time (see 7.3.4.3). 
• Level 2 will be documented for patients with higher functional status, walking 
outdoors, over ground surfaces, steep ramps, slopes and climbing stairs with 
step-over-step pattern. 
 
C Brace accommodation support shall follow standardized Ottobock procedures. 
 
7.3.4.3 Benchmarks 
Level 1 benchmarking requires independent donning/doffing of the orthosis, charging 
of the device (if applicable), transfers sit to stand / stand to sit, standing in the orthosis 
with or without assisted device for a minimum of 2 minutes, safe over ground ambula-
tion, ambulatory turns, to perform a swing phase, walking ramps with a low gradient 
and climbing stairs with step-to pattern. CPO or physical therapist shall do benchmark 
assessment.   

 
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C-Brace and KAFO/SCO home use may only be permitted after successful Level 1 
benchmark testing. C-Brace settings shall be documented by pdf-exports of the cockpit 
app and device read-out.  
Both devices shall be fitted with a step-count transponder. After 14 days, the patient 
will remove the step-count transponder from the orthosis and will send it back to the 
study site in a prepared envelope which will be handed to the patient after passing the 
benchmark criteria (Level 1). After having received the step-count transponder, the site 
investigator(s) and the sponsor will analyze the daily step count of the patient.    
 
7.3.5 Home use (both arms) / Follow-up phone calls  
Patients will be followed up by phone calls after discharge with KAFO/SCO or C-Brace: 
End of month 1, end of month 2. 
The purpose of these phone calls is to check if any notable adverse events, device mal-
functions or falls have occurred. Patients should be reminded during this call on use 
requirements and on the minimum use time of the device to avoid non- or misuse. The 
phone call shall follow a detailed procedure (see Annex III), results will be documented 
in a CRF and shall be conducted by the investigator.  
Patient is responsible to call the investigator in the case of malfunction, fall or other 
limiting event without any further delay. 
A patient diary is to be documented by the patient to ensure proper collection of fall 
information and to bring it at each visit.  
 
7.3.6 Study visit 1 
After 3 months of C-Brace or KAFO/SCO home use, respectively, a full performance as-
sessment using clinical tests and questionnaires, as defined in 8.2 will be performed. 
During study visit 1, patients will perform the following clinical tests and will fill out 
the following questionnaires: 
Clinical tests 
• Berg Balance Scale 
• Dynamic Gait Index (DGI) 
• Stair Assessment Index (SAI) 
• 6-minute walk test 
 

 
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Questionnaires 
• Changes in current assistive devices 
• Documentation of falls (Analysis of patient diary) 
• Documentation of fear of falling 
• Activity-specific balance confidence (ABC) Scale 
• EQ-5D-5L 
• Medical Outcomes Study Short Form (SF-36) 
• Orthotics & Prosthetics User Survey (OPUS) 
• Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 
• Reintegration to Normal Living (RNL) Index questionnaire 
• Work limitations questionnaires WLQ-25 
Device settings and step count shall be read out from C-Brace. An anamnestic interview 
is conducted to document possible changes in the medical history, specifically the use 
of assistive devices and to record AE´s, SAE`s and device malfunctions. 
Study visit 1 has to be planned 3 months after patients have passed the benchmarking 
criteria and have been discharged to use the orthosis. To facilitate the appointments 
with the patients, a time frame of -1 to +2 weeks around the scheduled visit is allowed.  
The following test sequence is recommended: 
Test sequence 
Documentation of falls 
Documentation of fear of falling 
Patient related outcome questions (only during study visit 2) 
Activity-specific balance confidence (ABC) Scale 
Berg Balance Scale (BBS) 
EQ-5D-5L 
Medical Outcomes Study Short Form (SF-36) 
Dynamic Gait Index (DGI) 
Stair Assessment Index (SAI) 
Orthotics & Prosthetics User Survey (OPUS) 
Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) 
6-minute walk test 

 
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Reintegration to Normal Living (RNL) Index questionnaire 
Work limitations questionnaires WLQ-25 
 
The clinical testing of the Berg Balance Scale and the Dynamic Gait Index is to be doc-
umented additionally by video. If possible, Stair Assessment Index and 6-minute walk 
test is also to be documented by video. Video files will be stored at the study site and 
transferred to the sponsor after completion of last-patient-last-visit milestone.  
7.3.7 Cross –over process 
Cross over of devices following procedure 7.3.4 Fitting and accommodation shall be 
performed. 
7.3.8 Wash out phase 
In the arm “C-Brace cross-over to KAFO/SCO”, a wash out phase of 4 weeks is imple-
mented to take a possible carry over effect into account. For safety reasons, wash out 
phase will begin after patient reaches benchmark level 1. 
In the arm KAFO/SCO crossover to C-Brace, no carry over effect is estimated, as it was 
not observed in previous studies. 
7.3.9 Study visit 2 
After 3 months of C-Brace or KAFO/SCO home use, full performance assessment using 
clinical tests and questionnaires, as defined in 8.2 will be performed. 
Procedures will follow the description in section 7.3.6 Study visit 1. Two individual 
questions to evaluate patient-related outcomes (PRO) will also be asked. 
7.3.10 
Patient´s C-Brace use after study end 
After the study documentation is completed, the individual study data can be used to 
support a reimbursement application according to local regulations for the time after 
the study. If such an application is filed, the device may remain with the patient until 
reimbursement is granted but for a maximum of 24 months. 
Patients who finish the study on a KAFO/SCO but want to return on C-Brace will be re-
trained. 
Patients who prefer to use their original orthosis shall also be re-accommodated. 
7.3.11 
Transfer of patients to C-Brace registry for long term follow up 
In the United States and Germany, a prospective registry with a 3-year observational 
period per patient is collecting data from clinical routine fitting.  

 
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Patients enrolled in a US or German study site can be transferred after study end and 
after signing an informed consent for the registry. In this case, patients should return to 
their original orthosis for at least 2 weeks before entering the registry.  
7.3.12 
Adaptations to the study procedure due to the COVID-19 pan-
demic 
Due to the outbreak of the COVID-19 pandemic, patients’ study visits were interrupted 
for the time of the lockdown. This had significant impact on the study procedure as 
well as on the patients’ individual study duration.  
The point of restarting patient assessments will be determined according to national, 
state and local regulations on COVID-19 containment. Starting dates may therefore be 
different per individual study site.  
In order to get comparable results before and after the lockdown, a full performance 
assessment using clinical tests and questionnaires, as defined in 8.2 will be performed. 
After the performance assessment, patients will be re-assessed regarding the ability to 
reach benchmark Level 1 as described in section 7.3.4.3. 
After successful Level 1 benchmark testing, patients will re-start the home-use phase in 
which they had been when the COVID-19 lockdown became effective. Home-use phase 
will be performed as described in section 7.3.5. 
If patients were in the wash-out phase or before the start of a home-use phase, patients 
will start with the following home-use phase according to protocol after successful Lev-
el 1 benchmark testing.  
Patients will receive a StepWatch as noted in the footnote to the Study Schedule in sec-
tion 8.3.  
A device read-out will be performed as described in section 8.2.2.4.    
Patients will continue the study as outlined in 7.3.  
In case of further lockdowns or in case local regulations prohibit patients’ study visits, 
the study visits shall be re-organized and patients will continue with the study follow-
ing the procedure described above.  

 
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Study Flow Chart  
 
 
 
Figure 4: Study flow chart 

 
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8 Outcomes measures 
8.1 General data collection 
Due to the nature of the study, several non-validated, self-designed questionnaires 
(SDQ) will be used as case report forms (CRF) to collect the necessary data.  
 
General patient and orthosis use data will include such information as: 
• Patients’ demography: patient age, gender, ethnicity, weight, height, BMI  
• Patients’ medical history: time since impairment, cause of limb impairment, 
limb(s) impaired, surgical history, comorbidities, medications, current orthosis 
fitting, use of aids, falls, duration of orthosis support since impairment, etc. 
 
Data collection is completed by video documentation of the performance tests. 
 
8.2 Outcome measures 
In terms of outcome measures, several questionnaires and performance-based 
measures will be used in the study.  
8.2.1 Primary study objective 
For the primary study objective, the static and dynamic balance will be assessed using 
the Berg Balance Scale (Version 2013) as primary efficacy endpoint. Measures will 
be performed and compared at first baseline, after 3 months with the current orthosis 
and after 3 months with C-Brace by a physician, orthotist or physical therapist when 
randomized to the first treatment group, and at baseline, after 3 months with C-Brace 
and after completion of 4 weeks wash out period and 3 months with the current ortho-
sis, when randomized to the second treatment group. 
The Berg Balance Scale is a 14-item scale designed to measure balance in adults in a 
clinical setting. When scoring, the lowest response category that applies should be 
recorded. In each item, points should be deducted if the time or distance requirements 
are not met, the patient’s performance requires supervision, or the patient requires 
assistance from support or examiner. 
The Berg Balance Scale was investigated in a variety of etiologies including patients 
suffering brain injury, spinal injuries, Parkinson`s Disease, stroke, osteoarthritis and 
vestibular disorders. It was also investigated in older adults and within geriatric care. 
The tool is recommended in intervention research studies. The minimal detectable 
change in elderly adults was determined to lie between 3.3 and 6.3. The BBS is associ-
ated with cut off scores in elderly adults with a score of 45 and lower indicating an in-

 
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creased risk of falling (8) and a score below 40 being associated with almost 100% fall 
risk (9).  
 
This investigation includes subjects with a BBS score < 45 and hence investigating sub-
jects that are believed to be at an increased fall risk. 
 
Administration and burden: Performance-based measure evaluated by physician, or-
thotist or physical therapist. 
 
 
 
8.2.2 Secondary study objectives 
8.2.2.1 Assessment of static and dynamic balance and functional mobility  
Assessment of static and dynamic balance and functional mobility is performed by us-
ing the activities-specific balance confidence (ABC) scale, the dynamic gait index (DGI), 
6-minute walk test, Stair Assessment Index (SAI) in patients using a C-Brace compared 
to KAFO/SCO. 
• Activity-specific balance confidence (ABC) Scale 
This test, along with a functional balance test, such as the Berg, will tell the clinician if 
their client is over- confident or under-confident about falling.  
The ABC is one of several tools designed to measure an individual’s confidence in 
his/her ability to perform daily activities. These tools were designed for use with older 
adults. The ABC was designed to include a wider continuum of activity difficulty and 
more detailed item descriptors than the Falls Efficacy Scale (FES). Fear of falling is im-
portant to assess because it is a likely confounder in measuring postural performance. 
Deterioration in balance may result from activity restriction mediated by the fear of fall-
ing. 
Administration and Burden: Patient self-administered; 5-10 min 
 
• Dynamic gait index (DGI) 
The Dynamic Gait Assessment is an 8-item test used to assess balance during walking 
tasks. It has a maximum score of 24 with each item being scored 0-3. It may be per-
formed with or without an assistive device; however, individuals lose a point on all 
items requiring a device. 
Administration and burden: Performance-based measure evaluated by physician, or-
thotist or physical therapist. 

 
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• 6-minute walk test 
The 6-minute walk test is performed as an objective evaluation of functional exercise 
capacity. The 6-minute walk test is easy to administer, well tolerated, and typically re-
flective of activities of daily living. The test measures the distance that the patient can 
walk on a flat, hard surface, indoors, in a period of 6 minutes. The walk test is patient 
self-paced and assesses the level of functional capacity. Patients are allowed to stop 
and rest during the test, however, the timer does not stop. If the patient is unable to 
complete the time, the time stopped is noted and reason for stopping prematurely is 
recorded. 
Administration and burden: Performance-based measure evaluated by physician, or-
thotist or physical therapist. 
• Stair Assessment Index (SAI) 
The Stair Assessment Index (10) is a 14-point ordinal scale (from 0 to 13) used to as-
sess different gait patterns during ascent or descent of stairs. It was developed to de-
tect differences in function with different knee units for transfemoral prosthetics. Stair 
ascent and stair descent pattern will be assessed separately. 
8.2.2.2 Measurement of safety and falls 
Patients will keep a patient diary in each home use period.  
To measure the safe use of C-Brace compared to KAFO/SCO, documentation will be 
done in the diary and information will be transferred to the CRF during study visits and 
phone calls. 
• Falls 
Principal investigator or his delegates interview patients every month for occurrence of 
falls, respectively occurrence of AEs/SAEs on the phone respectively ask for falls in 
study visits. 
In the case falling occurs, the following information is obtained from the patient and 
documented in the CRF per fall:  
Mild fall: no injury, bruising, abrasions, hematoma without physician / out-patient 
consultation 
Moderate fall: bruising, sprains, cuts, abrasions, or a reduction in physical function 
for at least three days, or if the participant sought out-patient medical help (11) 
Serious fall: fracture or admission to hospital or if any wounds needed stitches (su-
tures) (11) 
What was the consequence of the fall: 

 
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Diagnosis, office-based physician, ambulance visit, radiology, therapy, length of hospi-
tal stay, follow up visits. 
Frequency of falls are documented as well. 
• Patient reported outcomes questions regarding to fear of falling 
One question will address patients’ fear to experience a fall indoor and a second one to 
fall outdoor. The rating will be done on an 11-item scale (0 = no fear  to 10 = max. fear). 
In addition to each question, patients will be asked to explain in their own words the 
scenario of falling. 
Administration and Burden: Patient self-administered; 1 min. 
If an AE/SAE occurs, it will be processed as described in section 12.3. 
 
• Probability of falling more than once when using C-Brace compared to 
KAFO / SCO 
 The probability to fall more than once using C-Brace will be calculated and compared 
to the probability to fall more than once using KAFO / SCO. For details of the statistical 
analysis, see section 10.3.    
 
8.2.2.3 Quality of Life and Re-integration to normal living 
Measurement of quality of life and re-integration to normal living using C-Brace com-
pared to KAFO/SCO will be done using RNL index, EQ-5D-5L, WLQ-25, OPUS, SF-36, 
QUEST, and PROs. 
• Reintegration to Normal Living (RNL) Index questionnaire. 
The reintegration to normal living will be measured using the Reintegration to Normal 
Living (RNL) Index questionnaire. 
A measure of community reintegration, which covers areas such as participation in rec-
reational and social activities, movement within the community and the degree of com-
fort the individual has in his/her role in the family and with other relationships. 
11 items measuring satisfaction regarding perceived physical functioning, and social 
and emotional life. 
Internal consistency from a sample of persons with acute mobility impairments (includ-
ing persons with spinal cord injury), yielded a Cronbach α = .91. The RNL Index has 
been found to have good construct validity (12). 

 
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Scoring: There are different scoring algorithms for this measure. There is a 1) visual 
analog scale ranging from 0 to 10; 2) a three-point scoring system; and 3) a four-point 
scoring system. Regardless of the scoring system used, higher scores represent higher 
levels of participation. 
Administration and Burden: Patient self-administered; 30 min. 
The RNL was developed by Wood-Dauphinee, Opzoomer, Williams, Marchand, and 
Spitzer in 1988 (12). 
The RNL has been tested for use with individuals with stroke, malignant tumors, de-
generative heart disease, central nervous system disorders, arthritis, fractures and am-
putations; spinal cord injury; traumatic brain injury; rheumatoid arthritis; subarach-
noid hemorrhage; hip fracture; physical disability; and community-dwelling elderly 
(13). 
• EQ-5D-5L 
The EQ-5D-5L is a standardized measure of health status developed by the EuroQol 
group, applicable to a wide range of health conditions and treatments and has wide-
spread currency outside the profession. It is often referred to as a quality of life ques-
tionnaire. 
The EQ-5D-5L, is a very simple measure, which patients complete at the start and end 
of treatment. Its name means 'EuroQol – 5 Dimensions – 5 Levels' and comprises five 
dimensions of health: mobility, ability to self-care, ability to undertake usual activities, 
pain and discomfort, and anxiety and depression. There are five options (levels) under 
each domain. 
Administration and Burden: Patient self-administered; 10 min. 
• Work limitations questionnaires WLQ-25 
The Work Limitations Questionnaire (WLQ-25) was developed by Lerner and colleagues 
(14). It is one of the most commonly used questionnaires to evaluate at-work disability 
and productivity loss. It contains 25 items arranged under four subscales addressing 
four dimensions of job demands namely: time demands, physical demands, men-
tal/interpersonal demands, and output demands. The time demands subscale contains 
five items on punctuality, pacing, and productivity. The physical demands subscale 
has six items covering static positioning, moving around, lifting, repetitive movements, 
posture, and use of tools. The mental or interpersonal demands subscale contains nine 
items that assess concentration and on-the-job social interactions. The output demands 
subscale contains five items determining the volume and quality of work (14). 
• Orthotics & Prosthetics User Survey (OPUS) 

 
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The Orthotic and Prosthetics User Survey (15) is a self-report questionnaire, which is 
designed to evaluate the outcome of orthotic and prosthetic services. Three of the five 
domains will be administered: lower limb functional measure, health-related quality of 
life and satisfaction with device. The domains of upper limb functional measure and 
satisfaction with service are not applicable in this study. 
Administration and Burden: Patient self-administered; 15 min. 
• Medical Outcomes Study Short Form (SF-36) 
The SF-36 is a 36-item scale constructed to survey health status and quality of life. The 
SF-36 assesses eight health concepts: limitations in physical activities because of 
health problems; limitations in social activities because of physical or emotional prob-
lems; limitations in usual role activities because of physical health problems); bodily 
pain; general mental health (psychological distress and well-being); limitations in usu-
al role activities because of emotional problems; vitality (energy and fatigue); and gen-
eral health perceptions. The standard form of the instruments asks patients to reply to 
questions according to how they have felt over the previous week. The items use Likert-
type scales, some with 5 or 6 points and others with 2 or 3 points. Sample items include 
“How much bodily pain have you had during the past 4 weeks”, and “How much of the 
time during the past 4 weeks have you felt so down in the dumps nothing could cheer 
you up?” The SF-36 has been widely used and has excellent psychometrics. 
More information on Version 2 can be found on the SF-36 website: http://www.sf-
36.org/tools/sf36html 
Administration and Burden: Patient self-administered; 10 min. 
 
•  Quebec User Evaluation on Satisfaction with Assistive Technology (QUEST) 
The QUEST 2.0 evaluates a patient's satisfaction with various assistive technologies. 
The 12-item instrument is used to assess satisfaction with a specific assistive device; 
eight of these items assess characteristics of that assistive device in terms of the follow-
ing dimensions: dimensions (size), weight, adjustments; safety, durability, simplicity 
of use, comfort, and effectiveness.  
The remaining four items assess service and include service delivery, repairs and ser-
vice of the device, professionalism of service, follow-up service. 
Patients are asked to rate their satisfaction for the device on a five-point scale that 
ranges from "not satisfied" at all to "very satisfied". 
Finally, patients are asked to choose the three most important items related to the as-
sistive device in question. 
Administration and Burden: Patient self-administered; 10 min. 

 
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• 
 Patient-Related Outcome Questions 
Patients will be asked how the specific orthoses affected activities they enjoy and their 
quality of life (5 levels each, 2 questions). In addition to that, patients are asked to pro-
vide in a free text field information on these two topics. 
Administration and Burden: Patient self-administered; 4 min. 
 
8.2.2.4 
Device Read Outs 
• Setup App: 
A pdf-export and storage of the data file will be done at definitive fitting, every time a 
change in the settings is done and at the follow up visits.  
• Step Count 
A step count transponder will be fixed on C-Brace and on KAFO/SCO before starting the 
home use phase. It will be read out after each observational period (14 days).  
For details on the procedures, please refer to section 23.1 (Appendix I).  
8.2.2.5 General statement to self-administered patient questionnaires 
The patient fills in the questionnaires after instruction of the investigator. If a patient 
has an upper extremity impairment which does not allow him/her to fill in the ques-
tions, it is allowed that he/she answers orally and data entry will be performed by the 
investigator, the CPO or PT.  The patient is placed in a separate room. After filing out 
the investigator checks the questionnaires for completeness only. Questionnaires are 
available in English and German. If translation into another language is necessary, this 
will be done by an official translator. 
 
 

 
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8.3 Study schedule 
Visit 
IC 
Inclusion/ 
Exclusion 
Medical  
History 
BBS 
DGI 
SAI 
6MWT 
Step count 
ABC 
2PRO 
WLQ 
RNL 
EQ-5D 
SF-36 
OPUS 
QUEST 
C-Brace Set-
tings 
Fall history / 
Fear of falling 
Patient Diary 
AE/SAE/DD 
Screening 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
1st baseline 
 
 
 
x 
x 
x 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
 
x 
 
x 
2nd baseline 
 
 
 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 
 
x 
C-Brace Fitting1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Training/  
benchmarks(1) 
 
 
 
 
 
 
 
x2 
 
 
 
 
 
 
 
 
 
 
x 
x 
Phone call (1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
Phone call (2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
Additional Study visit (COVID-19) 
 
 
x 
x 
x 
x 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x3 
x 
x 
x 
Additional Training/ benchmarks 
(COVID-19)  
 
 
 
 
 
 
 
x2 
 
 
 
 
 
 
 
 
 
 
 
x 
Study visit (1) 
 
 
x 
x 
x 
x 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x3 
x 
x 
x 
Training/  
benchmarks (2) 
 
 
 
 
 
 
 
x2 
 
 
 
 
 
 
 
 
 
 
 
x 
Phone call (3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
Phone call (4) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
x 
x 
Additional Study visit (COVID-19)4 
 
 
x 
x 
x 
x 
x 
 
x 
 
x 
x 
x 
x 
x 
x 
x3 
x 
x 
x 
Additional Training/ benchmarks  
(COVID-19)4 
 
 
 
 
 
 
 
x2 
 
 
 
 
 
 
 
 
 
 
 
x 
Study visit (2) 
 
 
x 
x 
x 
x 
x 
 
x 
x 
x 
x 
x 
x 
x 
x 
x3 
x 
x 
x 
 
1Order shown for subjects randomized to start with C-Brace for whom casting is done after screening. C-Brace fitting to be done after Study Visit (1) for subjects starting with existing orthoses. 
2StepWatch affixed to either existing orthosis or C-Brace after benchmarks during training are achieved. 
3For subjects randomized to C-Brace only. 
4For subjects restarting after cross-over  

 
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9 Patient population 
9.1 Number of patients to enroll  
Up to 150 patients fulfilling the inclusion and exclusion criteria will be enrolled in the study. At least 
56 subjects passing screening will be randomized. All sites are allowed to recruit patients competi-
tively according to their possibilities. Patient screening and enrollment will be performed in close 
collaboration with the sponsor to avoid over-recruitment. 
Potential patients will be called by the participating centers and may be pre-screened for study eligi-
bility. In addition, patients contacting the centers or visiting them on a routine basis can be also pre-
screened. 
Once a potential participant using a unilateral KAFO or SCO has been identified, study clinician may 
contact the potential patient or study staff will contact the potential patient on behalf of the principal 
investigator, starting with a letter followed by a phone call to the potential patient. 
A screening log will be tracked. 
9.2 Duration individual patient’s participation 
Each patient should be observed 8-9 months depending on which orthosis is used before the crosso-
ver.  
9.3 Inclusion and Exclusion Criteria: 
Patients must meet all of the inclusion and must not meet any of the exclusion criteria to be regis-
tered to the study. 
Study treatment may not begin until a patient is registered. 
9.3.1 Inclusion criteria 
- 
Patient has been tested with the Trial Tool (DTO) and demonstrated the potential to utilize 
the C-Brace successfully (see section benchmarks: independent donning/doffing of the or-
thosis, charging of the device, transfers sit to stand/stand to sit, standing in the orthosis 
with or without assisted device for a minimum of 2 minutes, safe over ground ambulation, 
ambulatory turns and to perform a swing phase). 
- 
Patient has a BBS score < 45 
- 
Lower limb functional impairment according to CE label wording 
- 
Prior active and compliant use of unilateral or bilateral KAFO or SCO in the past 3 months 
prior to enrollment in the study 
- 
Patient meets minimum physical requirements to be fitted with a C-Brace, such as muscle 
status, joint mobility, leg axis and proper control of the orthosis must be guaranteed. 

 
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- 
The User must fulfill the physical and mental requirements for perceiving optical/acoustic 
signals and/or mechanical vibrations 
- 
The existing muscle strength of the hip extensors and flexors must permit the controlled 
swing-through of the limb (compensation using the hip is possible). 
- 
Patient´s commitment to use C-Brace 2 at least 1-2 hours per day 5 days per week- 
- 
Patient is ≥ 18 years old 
- 
Patient is willing and able to independently provide informed consent. 
- 
Person is willing to comply with study procedures 
9.3.2 Exclusion criteria 
- 
Patient who is not able to follow the entire study visits or is unwilling/unable to follow the 
instructions 
- 
Patient was not able to use DTO 
- 
Patient who is not using an orthosis at least 1 to 2 hours/ day for 5 days per week 
- 
Patient with body weight > 125 kg (includes body weight and heaviest object (weight) car-
ried) 
- 
Patient with Orthoprosthesis 
- 
Patient with flexion contracture in the knee and/or hip joint in excess of 10° 
- 
Patient with uncontrolled moderate to severe spasticity (relative contraindication moder-
ate spasticity) 
- 
Leg length discrepancy in excess of 15 com 
- 
Patient with unstable neurological or cardiovascular/pulmonary disease, cancer 
- 
Pregnancy 
- 
Patient using a C-Brace 
- 
Patient with known vertigo or with history of falls unrelated to orthosis use or unrelated to 
motor disability 
- 
Patient who has never been fitted an orthosis before 
- 
Patient is not able to answer the self-administered questionnaires independently; for pa-
tients with upper extremity impairment is it allowed to verbally answer the questions. 
- 
Patient participating already in a clinical study during this study´s duration 
- 
Patient participated in earlier C-Brace studies 
 
Additional determination of exclusion criteria for Austrian centers: 
Pregnant and nursing women are NOT allowed to participate in this study.  
Women of childbearing age are only allowed to participate in this study, if they have confirmed that 
they are not pregnant before the study (according to a pregnancy test). They will be asked to perform 
pregnancy tests once a month during the study. Female patients will be asked to inform the investi-

 
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gator immediately, if they become pregnant during the study, or suspect that they are pregnant. 
Their participation in the study will be terminated under these circumstances.  
9.3.3 Drop out or early termination of the study 
Patients can withdraw from the study at any time and for any reason. This decision has no impact on 
the patient’s medical care. In case of early termination, the investigator must document the reasons 
as completely as possible. The investigator can temporarily or permanently discontinue the patient's 
study participation for any reasons that are in the patient's best interest, particularly in cases of seri-
ous adverse events. If a patient is lost to follow-up, the investigator will use all available means to get 
into contact with him or her. After three weekly telephone reminders, the patient will be recorded as 
lost to follow-up. 
The investigator will fill in the reason for the drop out or early termination of follow-up in the case 
report form. Patient who drop out of the study may not keep the C-Brace up to 24 months as de-
scribed in section 7.3.10. 
 
Dropouts will be replaced until the milestone last patient in was reached. 
10 Statistics 
 
The goal of this study is to assess the improvement of static and dynamic balance by using C-Brace 
compared to KAFO/SCO which should in consequence help reduce the risk of falling/falls in these 
patients. 
10.1 Sample size calculation 
 
The sample size calculation is based on the hypothesis as described in 6.2 and crossover study de-
sign as described in 7. The number of recruited patients however will be larger than what would be 
needed to fulfill the requirements of the primary efficacy endpoint in order to achieve a higher power 
for any tests performed on secondary objectives and to improve the likelihood that the random allo-
cation of patients results in similar baseline characteristics in the compared group. 
Sample size calculation was performed with G*Power 3.1.9.7 or manually as described. 
 
 
 
 

 
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10.1.1 
Primary efficacy endpoint 
 
The efficacy of the microprocessor based C-Brace technology compared to a non-microprocessor con-
trolled KAFO/SCO will be determined through the detection of a statistically significant improvement 
of the Berg Balance Scale. 
One null-hypothesis will be tested in the confirmatory analysis: 
  
 
Sample size calculations are based on a mean group difference  = 6.6429 between the C-Brace tech-
nology compared to a non-microprocessor controlled KAFO/SCO and a standard deviation  = 
4.9085 of this difference. 
The estimations of the parameters come from paired observations in the RIC study combined with the 
paired observations of 4 patients from the Wien/Goettingen study (RIC combination study). In total, 
14 patients in the RIC combination study were considered to determine the estimates. All the includ-
ed patients displayed a Berg Balance Scale of less than 45. 
To test the hypothesis of an expected effect in one direction a one-tailed paired t-test will be used. 
At an  level of 0.05 and a power of 0.8, a total of 6.4557 of patients are needed as calculated from 
the t-distribution. Under the assumption of a dropout rate of 20% a total of 9 patients would need to 
be recruited. 
 
10.1.2 
Secondary endpoints 
An improvement in patients balance is hypothesized to aid the patients in their daily life and poten-
tially influence some of the other outcome measures collected in this study. These measures will be 
explored without a strict expectation for the magnitude of expected change. Due to the expected na-
ture of the distribution of the number of falls or rather the proportion of patients to fall more than 
once with the device C-Brace, these measurements would require the largest sample size in order to 
detect significant improvements at a reasonable power level. 
If the probability to fall more than once with the device C-Brace is significantly lower than the proba-
bility to fall more than once with the device KAFO/SCO it could be used as a supporting argument to 
relevance of a potentially identified improvement in the primary efficacy endpoint. Previous observa-
tions on the RIC combination data however revealed a low expectancy of the probabilities to fall 
more than once with either KAFO/SCO and C-Brace device during the observed time span. A proba-
bility to fall more than once of 
 with the device C-Brace and a probability to fall more 

 
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than once of 
 for the device KAFO/SCO was recorded for 
 paired observations in the RIC 
combination study. 
The sample size needed to detect a difference of 
 for the paired pro-
portions with on the basis of one-sided McNemar’s Z-test without continuity correction is calculated 
as 
 
where 
 
At a significance level of 0.05 and a power of 0.8, a total of 44.2386 of patients would be needed. 
Under the assumption of a dropout rate of 20% a total of 56 patients would need to be recruited. We 
recognize that the inclusion of a continuity correction may be more appropriate given the small pro-
portion to fall more than once with either type of device and that a shift in the expected proportions 
away from zero would drastically increase the number of patients needed to detect the difference to 
show a significant difference. Regardless the merit of the observing these proportions at a higher ab-
solute occurrence will yield a sound basis for future studies. For this reason, the number of patients 
to be included in the study is based on this value. 
 
10.2 Management of missing, unused or spurious data 
 
If data are missing, illegible or incoherent, requests for further information will be sent to the inves-
tigator in question. Although every effort will be made to ensure that each patient’s data is complete, 
some patients may not have data on one or more measures. 
For the intention-to treat analysis the missing data will be imputed. The imputation method will de-
pend on whether the missing data are at baseline or follow-up visit as well as the reason for the miss-
ing data as further described below. 
Missing baseline data for patients will be imputed. For missing data in any of the measurements 
which are taken again at the second baseline, these values might be used in place of the first base-
line measurement. Evaluation whether other missing baseline data might not be missing at random, 
will be done by exploring patterns of missing data within different measurements and patients for 
which data was collected. 
Strong evidence for missing data patterns within measurements of secondary interest may lead to the 
exclusion of such measurements for any supportive analysis and will be documented in the study 

 
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report accordingly. In case such a pattern is observed within the measurement of primary interest 
may lead to the study being declared invalid in regard to the analysis planned for it. 
Appropriate data management as defined in the protocol should reduce the chance of this being the 
case. Strong evidence for missing data patterns within patients of specific characteristics will be 
evaluated and might be indicative of a serious limitation to the study and could potentially lead to 
the study being declared invalid. Previous studies on the topic have not shown this to be very likely 
in the patients that fulfill the inclusion criteria of the study. Where data is assumed to be missing at 
random multiple imputation and a sensitivity analyses will be used. 
In order to perform a sensitivity analysis, patients who terminated treatment early, will be imputed 
using multiple imputation methods in order to substitute missing values. Here, multiple copies of the 
original dataset will be generated by replacing missing values using e.g. a multivariate normal dis-
tribution. Each of these complete sets will be analyzed as complete sets and the corresponding pa-
rameter and standard error estimates will be combined with taking the uncertainty of the imputation 
process into account. 
For the patients missing follow-up data, proportions of missingness, type of missing measurements, 
patient characteristics and baseline value levels will be explored in order to detect patterns of miss-
ing data. If data is assumed to be missing at random the following imputation strategy will be used. 
 
A linear mixed effects model with the outcome measure as dependent variable will be fitted to the 
data. This model will use the treatment group and period as fixed factor and the first baseline meas-
ure as covariate. Random patient effects will be introduced for the intercepts and thus taking the cor-
relation within patients into account. The analysis implicitly uses a weighted average to estimate the 
outcome measures, with estimations coming from the complete observations and from the observa-
tions with missing values. 
Missing data for study patients at follow-up on C-Brace, KAFO/SCO or both because they 1) died, 2) 
are lost to follow-up (LTFU), 3) withdrew from the study or were withdrawn from the study by the 
investigator, 4) miss the follow-up visit or 5) do not complete the outcome measure at follow-up, will 
be imputed by using a mixed model with a random intercept for patient and treatment group as pre-
dictor variables. 
The details of the imputations methods applied will be documented in the study report. 
 
10.3 Planned statistical analysis 
In general, the most suitable statistical analysis consistent with the form of data will be used and the 
underlying assumptions of the statistical method will be verified through appropriate pre-tests. 

 
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The analysis will be performed on the intention-to-treat (ITT) population and then on the per-
protocol (PP) population. The ITT population is defined as all the patients randomized into their ran-
domization group, regardless of the treatment received or their outcome in the study. The PP popula-
tion is defined as all the patients in the ITT population without any major protocol deviations 
For the outcomes measures being evaluated, three assessments are undertaken:  
after base line measurements with original orthosis (first baseline measurement)  
after first follow up measurement with the C-Brace or original orthosis  
after second follow-up measurement with the C-Brace or original orthosis 
Quantitative variables will be summarized using standard descriptive statistics (average, standard 
deviation, median, minimum and maximum, first and third quartile). Qualitative variables will be 
described using group sizes and frequencies. When relevant, 95%confidence intervals will be given. 
Patient characteristics at enrolment will be presented and compared in each group to ensure the 
groups are initially comparable. The features of any patients lost to follow-up will be studied and 
influence the imputation strategy as described in 10.2. 
Patient profile plots for the outcome measures in both treatment groups for all three assessments will 
be viewed, showing imputed values. Furthermore, the group means in each treatment group will be 
evaluated. Outcome measures will be visualized for the crossover periods in scatter plots of first fol-
low up measurement against second follow-up measurement in both treatment groups i.e. period vs 
period plots. 
 
10.3.1 
General patient and orthosis use data 
Assessments will be displayed in summary tables. 
 
10.3.2 
Primary efficacy outcome 
One null-hypothesis as outlined in section 10.1 will be tested in the confirmatory analysis. 
Absolute values and changes from first baseline and follow ups respectively will be presented for the 
Berg Balance Scale after 3 months of treatment using descriptive summary statistics for each treat-
ment period. Moreover, percentage changes from baseline and follow ups respectively will be dis-
played. 
The confirmatory inferential statistical evaluation of the primary outcome measure will be based on a 
linear mixed effects model with the Berg Balance Scale as dependent variable. This model will use 
the treatment group and period as fixed factor and the first baseline Berg Balance Scale as covariate. 
Random patient effects will be introduced for the intercepts and thus taking the correlation within 
patients into account. 

 
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The confirmatory analysis of the primary efficacy endpoint will be done for the intention-to-treat 
population. Additional efficacy analyses will be conducted for the per-protocol population. The p-
values of these analyses will be interpreted in the exploratory sense only. 
 
10.3.1 
Secondary outcome analysis 
Analyses for the secondary outcome measures will be performed for the intention-to-treat population 
as well as for the per-protocol population. All inferential analyses for the secondary efficacy varia-
bles will be interpreted in the exploratory sense. All secondary outcome measures will be evaluated 
by using descriptive statistics primarily, absolute values at each time point and if appropriate chang-
es from first baseline and follow ups respectively. These analyses will be performed in a similar way 
as the primary efficacy outcome using a linear mixed effects model when appropriate. 
Additional attention will be paid to the exploration of the measurements of safety and falls. The 
number of Falls is expected to be reduced in general by using a C-Brace, but the extent of a possible 
reduction remains uncertain. Therefore, frequency of falls, severity of falls, fall-related injuries, fear 
of falling and related treatment efforts will be explored in rigorously in order to formulate appropri-
ate hypothesis for future research. 
In the past the reduced probability of falling more than once by using C-Brace compared to KAFO / 
SCO showed the most promise as a reliable measure to compare the two device types, since it was 
less sensitive to outliers e.g. patients with a high number of falls on either device as compared to the 
total number of falls. However, sample sizes in prior research were relatively small and estimations 
for potential differences remain uncertain, albeit of great clinical interest. 
Therefore, we explore whether a reduction in the probability of falling more than once using the C-
Brace can be detected by a McNemar Test for paired proportions. This test will likely be underpow-
ered in comparison to the expected best-case scenario used in the sample size calculation and will be 
reported accordingly. 
 
10.3.2 
Randomization procedure 
Randomization will be performed by site in random permutated blocks of 6 by allocation order. A 
randomization sequence will be produced and integrated into the electronic case report form to de-
fine the randomized treatment order (X or Y device) and provide the investigator with this infor-
mation during the enrolment visit. 
 
10.4 Interim analysis 
An interim analysis will be performed after at least 35 patients have completed the study. After the 
interim analysis, it will be decided whether: 1) the sample size must be increased 2) the study will be 

 
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stopped early for futility, or 3) interim hypothesis testing will be done for the primary objective and 
select secondary objectives. 
 
The interim analysis will be performed for the primary endpoint (BBS). A statistical power calcula-
tion will be performed based on the observed intraindividual changes (IIC) between C-Brace and 
KAFO arms. The following rules will be applied: 
1. If the power based on observed mean and standard deviation for the BBS IIC for the intended 
target of 56 subjects is less than 0.9, the proposed sample size for the study may be increased. 
2. If the observed mean IIC is less than 3, the study may be stopped for futility, since this differ-
ence is of no clinical relevance. 
3. If the power based on observed mean and standard deviation for the BBS IIC with the interim 
analysis cohort of at least 35 subjects is greater than 0.95, hypothesis testing will be per-
formed at the alpha = 0.02 level to determine statistical significance. In this case, the primary 
objective will be analyzed at the 0.03 level for the final analysis of the full study cohort at the 
completion of the study to maintain an overall Type I error rate of 5%. If the power is less than 
0.95, hypothesis testing will only be performed at the conclusion of the study and statistical 
significance determined using alpha = 0.05. 
 
Conditional hypothesis testing may be performed for select secondary objectives using the same 
method described in rule 3 above. 

 
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11 Risk and benefit of the investigation device and clinical investiga-
tion 
C-Brace is a CE-marked class I medical device. Risk analysis has been conducted and identified risks 
such as blocking of flexion in knee joints when descending stairs or ramps, unintentional locking 
during sitting, flexion resistance is not reduced when walking on level ground (swing phase), insuf-
ficient extension of knee joint in the stance phase, insufficient extension of the orthosis during 
standing up. All those identified risk could lead to a fall. After implementation of appropriate 
measures, the risk analysis concluded that the remaining risks are either acceptable or ALARP (as 
low as reasonably practicable). 
 
In this clinical study, patients will be randomly assigned to two treatment groups. Treatment group 1 
will start with 3 months usage of the patients’ KAFO or SCO. The patients will then move to a 3-
month period of C-Brace use. Treatment group 2 will start with 3 months of C-Brace use and will then 
enter into a 4-week washout period before moving to a 3-month period of KAFO/SCO use. This ran-
domization will not add any additional risks to the patients since both groups will use both devices 
for the same period. 
 
Patients enrolled in the study will enter with their current orthosis (KAFO/SCO). Before performing 
the clinical tests, patients will receive up to 10h of accommodation training and will be bench-
marked according to their ability to use their orthosis. When entering the C-Brace group, patients will 
again receive up to 10h of accommodation support and an assessment. Patients enrolled in the study 
who will start with C-Brace, will receive accommodation support and assessment. When switching 
back to their regular orthosis (KAFO/SCO) they will again receive accommodation and assessment. 
Therefore, the risks due to switching of the devices in the clinical study are mitigated. 
 
The expected benefit of C-Brace to the patients participating in this study will be comparable to the 
ones published on C-Brace. The literature published on C-Brace suggests that microprocessor con-
trolled SSCOs offer benefits during walking on level ground, stairs and ramps when compared to 
conventional KAFOs such as locked KAFOs and SCOs. Biomechanical analysis showed that more 
physiological swing and stance phase during level walking is possible with C-Brace (Schmalz 2016). 
Walking on ramps and stairs was also more physiological allowing step-over-step descent. The load 
on the contralateral limb was reduced. C-Brace also resulted in improved safety and reduction in dif-
ficulty of performing activities of daily living (Pröbsting 2016). Subjects report of 91% of the ADLs 
being safer and 76% of the ADLs less difficult to perform with C-Brace in comparison to their previ-
ous orthosis. Greatest functional gain was achieved in the categories Family and Social Life and 
Sports and Leisure activities. Significant improvements were achieved in the domains of ambulation, 
paretic limb health, well-being and disturbing sounds of the orthosis. 

 
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The new version of C-Brace is smaller and reduced in weight. Furthermore, due to an improved sen-
sor system in the joint unit, sensor at the ankle become obsolete and therefore the design of the or-
thotic shells can be better adapted to the individual anatomy. Therefore, the benefits of the new C-
Brace should be better or at least in the range of those reported for the original C-Brace. The sensor 
technology that does not require an ankle sensor is already applied in the C-Leg 4. First clinical re-
sults showed high satisfaction (94% of users reported to be either satisfied or very satisfied) and 72% 
of users reported better or much better swing initiation compared to their previous prosthesis (Kraft 
2015, Wismer 2016).  
 
Therefore, it can be concluded that the risks associated with the use of the device are acceptable 
when weights against the benefits that this research can generate in terms of further development of 
C-Brace to the subjects and patient population in general.  
 
Risk-benefit assessment of the clinical investigation during the COVID-19 pandemic situation 
 
In this clinical study, patients are asked to visit the study site for 6 visits, as well as for additional 
visits if required by the site for the purpose of fitting of assistive devices (KAFO/SCO or C-Brace). In 
most likely all cases, patients will have to travel to get to the respective study site.  
 
All patient appointments will be done in accordance with the effective national, state and local regu-
lations on contact and /or travel restrictions due to the COVID-19 pandemic. Whenever possible, the 
number of appointments at the study site will be reduced and patient assessments will be managed 
over the phone (unless the patient needs assistance with their medical device).  
 
Prior to arriving to the first visit since the start of the COVID-19 pandemic, a risk factors assessment 
shall be conducted in accordance with the procedures valid in the sites in order to decide whether 
the patient should attend the next visit at the site (i.e. to continue in the study for patients already 
enrolled or to attend an enrollment visit for patients interested in participating in the study).  
 
During patient visits, every effort will be taken to minimize a potential infection risk by:  
• limiting the number of staff to a minimum, 
• providing sufficient protection material to the patients as well as to the staff (gloves, coats, 
face masks, hand hygiene practices, cleaning of assistive devices and surfaces, and other pre-
cautions that will be taken before and after every patient visit),  
• minimizing the length of stay necessary for the patients and  
• maximizing the distance between patients and staff as much as possible.  
 

 
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In case of increasing health risk or for any other reason, all enrolled subjects may withdraw from the 
study at any time. 
 
Therefore, it can be concluded that, given that all mitigation measures described above are taken, 
the risks associated with a study visit during the COVID-19 pandemic are acceptable when weighed 
against the benefits that this research can generate for the individual and the population in general. 
 
If the study is still running after the COVID-19 pandemic situation, some of the precautions will not 
be necessary anymore. In this case, potential subjects will be invited to attend an information meet-
ing with the Principal Investigator (PI). If the subject is considered by the PI to be eligible for partici-
pation in the study, he/she will be fully informed about the study and given sufficient time to con-
sider and given an opportunity to ask questions or to discuss participation with his/her general prac-
titioner or therapist. Subjects who wish to enter the trial will then sign the consent form and subse-
quently be enrolled. 
 

 
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12 Management of adverse events 
 
12.1 Description of possible adverse events & adverse device effects 
Falls are expected to be reduced in general using a C-Brace, however in patients with limb impair-
ment falls might occur. 
 
12.2 Definitions 
 
The investigator is responsible for recording all AEs diagnosed in the frame of study visits, reported 
by the participant or communicated to the investigator by a third person during the study period. 
Adverse Event 
An AE is (acc. to ISO 14155-2020) any untoward medical occurrence, unintended disease or injury, 
or untoward clinical sign (including abnormal laboratory findings) in patients, users or other per-
sons, whether or not related to the investigational medical device 
 
A Serious Adverse Event (SAE) is an Adverse Event that (acc. to ISO 14155-2020): 
1. led to a death; 
2. led to a serious deterioration in the health of the patient that 
- 
results in a life-threatening illness or injury; 
- 
results in a permanent impairment of a body structure or a body function; 
- 
requires hospitalization or prolongation of existing hospitalization; 
- 
results in medical or surgical intervention to prevent permanent impairment to body struc-
ture or a body function; or led to 
3. fetal distress, fetal death or a congenital abnormality or birth defect. (Ref ISO/DIS 14155-
2020) 
Adverse Device Effects (ADE): adverse event related to the use of an investigational medical device. 
This includes adverse events resulting from insufficient or inadequate instructions for use, deploy-
ment, implantation, installation, or operation, or any malfunction of the investigational medical de-
vice, as well as, any event resulting from use error or from intentional misuse of the investigational 
medical device (Ref ISO/DIS 14155-2020). 

 
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Serious Adverse Device Effect (SADE): adverse device effect that has resulted in any of the conse-
quences characteristic of a serious adverse event. (Ref ISO/DIS 14155-2020) 
Unanticipated Serious Adverse Device Effect (USADE): serious adverse device effect, which by its 
nature, incidence, severity or outcome has not been identified in the current version of the risk anal-
ysis report (Ref ISO/DIS 14155-2020). 
Device deficiency represents inadequacy of a medical device with respect to its identity, quality, du-
rability, reliability, safety or performance. Device deficiencies include malfunctions, use errors, and 
inadequate labeling (Ref ISO/DIS 14155-2020). 
 
12.2.1 
Additional national definitions 
Germany 
Notwithstanding the definitions in ISO/DIS 14155-2020, the following definitions apply according 
to Medizinprodukte Sicherheitsplanverordnung (MPSV) and have to be used for categorization of 
AEs and SAEs in Germany: 
 
According to §2 (5) MPSV a serious adverse event is "... any unintentional event occurring in a clini-
cal trial or performance evaluation subject to authorization which has led, could have led or could 
lead directly or indirectly to the death or serious deterioration of the state of health of a subject, user 
or other person without taking into account whether the event was caused by the medical device; the 
foregoing applies mutatis mutandis to serious adverse events that have occurred in a clinical trial or 
performance evaluation for which an exemption from the licensing requirement pursuant to § 20 (1) 
sentence 2 of the “Medizinproduktegesetz" has been granted. 
According to §2 (1) MPSV an event is "... a malfunction, a failure, a change in features or perfor-
mance or an improper labelling or instructions for use of a medical device, which has led, could have 
led or could lead directly or indirectly to the death or serious deterioration of the state of health of a 
patient, user or other person; a malfunction is also considered to be a lack of fitness for use, which 
causes misuse.". 
 
Netherlands 
Definitions for AE/SAE in the Netherlands follow the definitions in MEDDEV 2.7/3 rev.3 which are in 
line with the definitions in ISO 14155 2020. Therefore, no national definitions for AE/SAE are neces-
sary.  
 
United States of America 

 
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Definitions for AE/SAE in the US follow the definitions in ISO 14155. Therefore, no national defini-
tions for AE/SAE are necessary.  
 
Austria 
Notwithstanding the definitions of ISO14155-2020, the following definition applies according to the 
Austrian “Medizinproduktegesetz”: 
Austria §2(17) MPG: Adverse Device Effect ("Nebenwirkung") is any undesirable clinical event occur-
ring under and related to the normal conditions of use of a medical device, i.e., a device-related ad-
verse event. 
 
12.3 Documentation of Adverse Events / Serious Adverse Events 
 
All AEs are to be recorded once only on the appropriate AE pages in the CRF. The investigator should 
complete all the details requested including dates of onset, severity, corrective therapies given, out-
come and opinion as to whether the AE is likely to be device-related. Each event should be recorded 
separately.  
In the case of a SAE, the investigator must complete, sign and date the SAE pages from the CRF, 
check that the data are consistent, and send a copy without any further delay to the contact specified 
below: 
 
Ottobock SE & Co. KGaA, Max-Näder-Str. 15, 37115 Duderstadt  
Fax: +49 5527 848-83402 
   
Where additional follow-up information is required, this should be completed on a SAE follow-up 
form, a copy sent to the Sponsor and the original placed in the SAE section of the CRF.  
12.4 Reporting of Adverse Events / Adverse Device Effects 
 
During the entire patient follow-up period, any AE or ADE that occurs to a person during the study 
period must be followed until it resolves or is deemed permanent. Any AE or ADE, regardless of 
whether it is related to the study, must be documented. Any SAE (device/procedure-related or not 
device/procedure-related) must be reported to the sponsor on the form provided for this purpose in 
the case report form without any further delay from the moment of occurrence (or as soon as the in-
vestigator becomes aware of it). The initial report may be followed by relevant additional information 
within 7 days. 
In the case of SAE and SADE, sponsor and investigator together complete the reporting forms for Eth-
ics Committee(s) and competent authority. Both sponsor and investigator evaluate the causal rela-

 
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tionship between the AE and investigational device and if different note this on the form. After sign-
ing the forms, either sponsor or investigator forwards it to the Ethics Committee and regulatory au-
thority, if applicable. In case of multicenter and/or multinational studies, the sponsor has responsi-
bility to inform other centers and relevant Ethics Committees / authorities.  
12.4.1 
Additional national requirements for reporting of adverse events 
Germany 
Notwithstanding the definitions in ISO/DIS 14155-2011, the following definitions apply according 
to Medizinprodukte Sicherheitsplanverordnung (MPSV) and have to be used for reporting AEs and 
SAEs in Germany: 
After the sponsor has received a notification of an SAE that cannot be ruled out as being related to 
the medical device under investigation, a reference product or the therapeutic or diagnostic 
measures applied in the clinical trial or the other conditions for conducting the clinical trial, this 
must be reported to the responsible competent authority (BfArM) without further delay. The follow-
ing form must be used for this purpose: 
https://www.bfarm.de/SharedDocs/Formulare/DE/Medizinprodukte/Meldeformular_Klinische-
Pruef_SAE.html 
All other SAEs for which a connection with the medical device under investigation, a reference prod-
uct or the therapeutic or diagnostic measures applied in the clinical trial or the other conditions for 
conducting the clinical trial can be ruled out must be reported to the competent authority (BfArM) on 
a quarterly basis. The following form must be used for this purpose: 
http://ec.europa.eu/DocsRoom/documents/16477/attachments/2/translations 
If an SAE occurs in the context of a clinical study with a CE-certified medical device in which a con-
nection with the test product cannot be ruled out, this must be reported immediately to the compe-
tent authority (BfArM) as an "incident" in accordance with Sections §3 and §5 MPSV as soon as it 
becomes known. If a serious undesirable event also constitutes an incident, the sponsor may also 
fulfil its obligation to report the incident by submitting an SAE report in accordance with §3 (5) 
MPSV. In the report it must be made clear that the obligation to report an incident in accordance with 
§3 (1) MPSV is also fulfilled. 
Netherlands 
The sponsor must immediately inform the Inspectorate (within two working days and not later than 
four calendar days) of SAEs which indicate an inevitable risk of death, serious injuries or serious ill-
ness, and requiring prompt remedial action for patients. 

 
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This includes SAEs that result in (temporary) suspension of inclusion of patients in the clinical inves-
tigation, discontinuation of the clinical investigation (temporarily or otherwise), or modification of 
the medical device. 
Events that were reasonably foreseeable and are described as such in the Protocol and the patient 
information (“calculated risks”) are excluded from the above requirements, insofar as they do not 
lead to the (temporary) suspension or discontinuation of the clinical investigation or to modification 
of the medical device. 
MEDDEV 2.7/3 stipulates that all other reportable events (see section 4 of MEDDEV 2.7/3) must be 
reported within no more than seven days. The Inspectorate applies a less intensive term in this re-
spect. SAEs that do not fall under item 2 above may be reported quarterly in their totality to the In-
spectorate by means of the reporting table, which can be found on the website of the European 
Commission. 
Austria 
The sponsor of a clinical investigation has to fully record all serious adverse events and notify them 
immediately to the BASG and to all other competent authorities in those member states of the EEA in 
which the clinical investigation is being performed.  
Note: 
• 
Where a medical condition is already established prior to the initiation of a clinical investigation 
and surgery has been scheduled to amend it, the definition of an adverse event according to 
MPG is not fulfilled and reporting to the BASG as SAE is not required. If the medical condition 
arises during the conduct of the clinical investigation, then SAE reporting to the BASG is re-
quired  
• 
If a hospitalization preceded or was already planned prior to the initiation of a clinical investiga-
tion the definition of adverse event according to MPG is not fulfilled, no reporting as SAE is re-
quired. However, if unplanned hospitalization occurs during the conduct of the clinical investi-
gation, SAE reporting to the BASG is required - whether or not causality has been established 
with the investigated device.  
 
SAE and SADE that result in immediate risk of death, serious injury or illness will be reported with-
out delay, at least within 2 calendar days to EK and BASG. All other SAEs and SADEs will be reported 
by sponsor within 7 days. 
All incidents (Zwischenfall) will be reported by sponsor to competent authority (BASG) and ethics 
committee as specified in MPG §70(1) MPG. 

 
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13 Monitoring  
The Clinical Project Manager will ensure proper monitoring of the study with special attention to ver-
ification of all clinical requirements, adherence to protocol, good clinical practices and compliance 
with applicable government and institutional regulations. 
Authorized, qualified representatives of the sponsor or authorized, qualified staff of a CRO commis-
sioned by the sponsor will visit the investigational site in regular intervals to verify the adherence to 
the clinical investigation plan and local legal requirements, to perform source data verification and 
to assist the investigator in his study related activities. 
The monitor will at least document protocol deviations to informed consent procedures, SAE report-
ing within required timelines and investigational product handling in the Protocol Deviations Log. 
The Protocol Deviations Log will be consecutively completed during the ongoing trial as an appendix 
to the Monitoring Visit Report. Protocol deviations detected by data management should be notified 
to the sponsor and to the monitor. The monitor or the data management will notify the investigator of 
deviations in writing.  
The following visits are planned: site qualification and feasibility, site initiation, routine visits and 
closeout visit. More details are given in the Monitoring Plan.  
Monitor is responsible for reviewing the data for completeness and clarity. The details are provided 
in the Monitoring Plan. The investigator(s) commits to allowing audits to be performed by the spon-
sor and to potential inspections being performed by competent authorities. All data, documents and 
reports can be suspect to audits and regulatory inspections. 
13.1 Direct Access to Source Data/Documents 
The investigator will permit study-related monitoring, audits, EC review and regulatory inspections 
and provide access to primary data (i.e. source data) which supports the data on the CRFs for the 
study, e.g. general practice charts, hospital notes, appointment books, original laboratory records to 
sponsor, authorized representatives of the sponsor such as study monitors and auditors, and appro-
priate regulatory authorities.   
Any party with access to study records shall take all reasonable precautions consistent with applica-
ble regulatory requirements to maintain the confidentiality of patient identifying information and 
sponsor’s confidential and/or proprietary information.   

 
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13.2 Source Documents and Source Data 
Source documents are defined as printed, optical or electronic documents containing source data 
(e.g. hospital records, laboratory notes, device accountability records, photographic negatives, radi-
ographs, records kept at the investigation site, at the laboratories and at the medico-technical de-
partments involved in the clinical investigation) (ISO 14155:2020). 
The eCRF is used as source data. 
 
14 Data management 
Data collection 
A web-based standardized electronic case report form (eCRF) (eClinicalOS IBM 2.0) and a paper-
based CRF will be used to document the patients’ data during the course of the study. Both CRFs are 
designed to accommodate the specific features of the study design. All data obtained after the patient 
has given informed consent must be recorded in the CRFs. The investigator will assure that all data 
are entered promptly, completely, and accurately according to the CRF instructions, and conform to 
source documents. Data for all patients screened for study inclusion have to be documented on a 
respective form. 
The eCRF and a paper-based CRF are used as source data. 
Case Report Forms (CRFs) must be completed after every visit for each patient enrolled into the study 
within 4 weeks. 
Only investigators and authorized designees are allowed to make entries in the CRF. This will be reg-
ulated by appropriate reading and writing access. Completed CRFs per visit, must be electronically 
signed by the investigator or authorized designee. Any change or addition will be recorded by an au-
dit trail system. 
All forms must be filled out completely; data are checked electronically for consistency and plausi-
bility.   
It is the investigators’ obligation to assure documentation of all relevant data in the patient’s file, 
such as medical history, concomitant diseases, date of study enrolment, visit dates, results of exami-
nations, administrations of medication, and AEs. 
Worksheets are allowed as backup, information must be entered electronically. 

 
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Self-reported patient questionnaires are filled out by patient. Investigator checks when he receives 
the questionnaires back, if they are completed and refer to the patient to complete missing items if 
applicable.  
Data management procedures 
All data management activities will be conducted by the sponsor or a sponsor’s designee following 
their SOPs. The database will be built by the sponsor or a sponsor’s designee. 
Details on data handling will be described in the Data Management Plan. The sponsor or the spon-
sor’s designee will handle the data cleaning process, including logical check, and query processes. 
Computerized validation check programs on completeness, correctness, plausibility (such as range 
checks, crosschecks) will verify the data according to the Data Validation Plan. All identified dis-
crepancies will be addressed to the investigator. 
The database will be hard locked after all the changes following the data review meeting have been 
done and the database is considered complete and accurate. All changes will be tracked (audit trail).  
 
15 Documentation and administration 
15.1 Investigator’s Brochure 
The investigator shall be informed by means of the Investigator’s Brochure on the preclinical and 
clinical state of knowledge concerning the Investigational Product. In so far as important new infor-
mation arises, the information for the investigators will be updated on a regular basis. 
15.2 Deviations from Clinical Study Protocol 
A clinical study protocol deviation is any instance of failure to follow, intentionally or unintentional-
ly, the requirements of the clinical study protocol (ISO 14155:2020).  
Ottobock is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions (e.g. amend the clinical study protocol, conduct addi-
tional training, etc.). Repetitive or serious investigator compliance issues may require initiation of a 
corrective action plan with the investigator, and in some cases, necessitate suspending site enroll-
ment until the problem is resolved or ultimately terminating the investigator’s participation in the 
study. 
Major clinical study protocol deviations represent non-adherence to one or more inclusion and/or 
exclusion criteria or are considered to affect the safety and well-being of the patient. Major clinical 

 
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study protocol deviations increase the risk, decrease the benefit and/or affect the participant’s rights, 
safety, and/or the integrity of the resultant data. They also may result from evidence of willful or 
knowing misconduct on the part of the investigator, or from ignorance of established research, med-
ical, and ethical principles. 
Examples for major deviations:  
• 
Patients enrolled prior to EC notification of approval or after expiration of approval  
• 
Enrollment of a patient outside the inclusion/exclusion criteria  
• 
Use of an unapproved or expired informed consent form  
• 
Inadequate/improper informed consent procedures  
• 
Inclusion of patients who have not provided written consent  
• 
Failure to maintain adequate patient records or proper study documentation 
It is the responsibility of the Investigator not to deviate from the protocol approved by the EC, except 
as necessary to avoid an immediate hazard to the participant.  
 
Procedure: 
Should a deviation from the clinical study protocol be deemed crucial for the safety and well-being of 
a particular patient, such a departure will be instituted for that patient only. The Investigator should 
document in the patient’s CRF and in the patient´s medical file the reason(s) for the deviation. Each 
participating center must adhere to the policies and guidelines established by their EC for the fre-
quency and format of reporting clinical study protocol deviations.  
Major clinical study protocol deviations are to be reported to the study Sponsor as soon as the Inves-
tigator or study personnel become aware of their occurrence. 
Clinical study protocol deviations will be documented and reported at the time of continuing review 
report. 
 
15.3 Amendments to the Clinical Study Protocol 
All amendments to the clinical study protocol should be agreed between the Sponsor and the Inves-
tigator and be recorded with a justification for the amendment. The Investigator or the Sponsor will 
not implement any deviation from, or changes of, the clinical study protocol without mutual agree-
ment and review/approval from the EC, and other agencies as required, of a proposed amendment. 
The only exceptions are where necessary to eliminate an immediate safety hazard to study patients, 

 
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or when the changes involve only administrative aspects of the clinical study (e.g. change in moni-
tor(s), change of telephone number(s)). 
The party initiating an amendment must confirm it clearly in writing and it must be signed and dated 
by the Sponsor, the Coordinating Investigator and the Principal Investigators. Clinical study protocol 
amendments will be submitted to the appropriate ECs and competent authorities in line with perti-
nent national regulatory requirements. 
 
15.4 Final Report 
After the statistical analysis, the final report for the study is prepared and has to be signed by the 
study coordinating investigator, the principal investigators and the sponsor. 
 
16 Study Discontinuation 
16.1 Investigational Site Termination 
Otto Bock Healthcare Products GmbH reserves the right to terminate an investigational site for any of 
the following reasons: 
• Failure to secure Informed Consent from a patient enrolled into the study 
• Repeated protocol deviations 
• Repeated failure to complete Case Record Forms on a timely basis 
• The investigator requests discontinuation 
If the study is prematurely terminated or suspended for any reason, study participants will be in-
formed promptly and, where required by the applicable regulatory requirement(s), the relevant regu-
latory authority(ies) will be informed. The ethics committees will be informed promptly and provided 
with a detailed written explanation for the termination or suspension. 
 
16.2 Premature discontinuation of the complete study 
If the study is prematurely terminated or suspended, the Project Manager, on behalf of Otto Bock 
Healthcare Products GmbH, will inform promptly the investigator/institution, and, if applicable, the 
regulatory authority(ies) of the termination of suspension and the reason(s) for the termination or 
suspension. The ethics committees will be informed promptly and provided with a detailed written 
explanation for the termination or suspension by the Project Manager, on behalf of Otto Bock 
Healthcare Products GmbH, or by the investigator/institution, as specified by the applicable regula-
tory requirement(s).  

 
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Some of the reasons for premature termination of the study are: 
• If the safety of the participants is jeopardized (eh. many falls and stumbles reported), and 
• If the users cannot show “proficient use” of the intervention devices.  
 
Please see section 18 for publication strategy after premature discontinuation.  
16.3 Requirements for patient follow up 
In case of premature discontinuation of the study, the study site will contact the patients enrolled in 
the study. The patients will return the C-Brace orthosis to the study center. To ensure a safe use of 
their current orthosis (KAFO/SCO), patients will get an accommodation support and will be assessed 
for their orthosis use by a CPO or PT. Since this orthosis represents their orthosis before entering in 
the study, no additional risk for the patient is assumed.   
In case of premature discontinuation of the study, available study data can be used to support a re-
imbursement application according to local regulations for the time after the study. If such an appli-
cation is filed, the device may remain with the patient until reimbursement is granted but for a max-
imum of 24 months. Patients will be re-trained or re-accommodated. All procedures described in sec-
tion 7.3.10 will apply.  
17 Ethical considerations 
17.1 Independent ethics committee  
In accordance with current laws of the countries where study will be conducted, the protocol will be 
submitted to the Research Ethics Committee for an opinion. The study will start once approved the 
study and authorities, if applicable. Any necessary extension or renewal of the ethics committee ap-
proval must be obtained. Change(s) to any aspect of the trial, such as modification(s) of the protocol, 
the written informed consent form, the written information provided to patients, and/or other proce-
dures must be approved, in writing, by the ethics committee. 
 
Ethics committee will be informed promptly of any new information that may adversely affect the 
safety of patients or the conduct of the trial. Similarly, any written summaries of the trial status will 
be reported to the ethics committee annually, or more frequently, if requested by the ethics commit-
tee. Upon completion of the trial, the ethics committee with be provided with a study report. 
17.2 Ethical conduct of the study 
The Guidelines of the World Medical Association Declaration of Helsinki, the Guidelines of GCP, and 
ISO 14155-2020 as well as the demands of national drug and data protection laws and other appli-
cable regulatory requirements will be strictly followed 

 
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The investigator(s) must fulfill all requirements as stated in ISO 14155-1 and national law. He/she is 
responsible for the conduct of the clinical trial and is responsible for the clinical well-being of the 
patients involved. The investigator(s) is not allowed to deviate from the CIP. Request for changes 
needs to be first discussed with the sponsor who will if required request permission from the Ethics 
Committee.  In case, deviation was not possible to omit (i.e. to protect rights, safety, well-being of 
patients), they need to be documented and reported.    
The sponsor must fulfill the requirements and responsibilities as stated in ISO 14155-1 and national 
law. 
 
17.3 Patient information and informed consent 
The investigator is responsible for ensuring that no patient is patient to any study-related examina-
tion or activity before that patient and/or legal guardian has given informed consent. Written con-
sent must be given by the patient, after the receipt of detailed information. The verbal explanation 
will cover all the elements specified in the written information provided for the patient.  
 
The investigator will inform the patient of the aims, methods, anticipated benefits and potential haz-
ards of the study including any discomfort it may entail. The patient must be given every opportunity 
to clarify any points he/she does not understand and if necessary, ask for more information. At the 
end of the interview, the patient may be given time to reflect if this is required, or more time for dis-
cussion with family, caregivers or their own General Practitioner. Patients and/or legal guardian will 
be required to sign and date the informed consent form. After all parties have signed and dated the 
informed consent, a copy will be given to the patients while the original will be kept and archived by 
the investigator. 
 
It should be emphasized that the patient is at liberty to withdraw their consent to participate at any 
time, without penalty, loss of benefits or normal medical care to which the patient is otherwise enti-
tled. Patients who refuse to give or withdraw written informed consent may not be included or con-
tinue in this study. 
 
COVID-19 Risk Factors Assessment and patient re-consent 
Prior to arriving to a study site for the first visit since the start of the COVID-19 pandemic (i.e. first 
visit at the site for patients not yet enrolled, or follow-up visit for patients already enrolled), an in-
formed consent form will be sent to the patient per mail or email. After having received the informed 
consent form, the investigator will contact individual patient via phone to conduct the informed con-
sent process. A patient who decides to continue in the study or remains interested in enrolling in the 
study will be asked to provide his/her consent verbally. Following verbal consent, the investigator 
will perform a risk assessment with the patient via phone. During this assessment the patient will be 

 
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asked about his/her exposure to COVID-19 (i.e. potential contact with infected subjects, potential 
COVID-19 test) along with other general health questions (i.e. age, lung disease, kidney disease, 
cancer, obesity) known to be placing the patient at an increased risk in accordance with those identi-
fied by the Robert Koch Institute (RKI) (Germany), , National Institute for Public Health and the Envi-
ronment (The Netherlands), Federal Ministry Republic of Austria, Social Affairs, Health, Care and 
Consumer Protection (Austria). If no risk factors are identified and the patient is willing to continue 
or to enroll in the study, an appointment will be made for an on-site study visit. In case the investiga-
tor identifies one or more risk factors during the phone contact, the decision to continue or to enroll 
in the study will be deferred to the site Principal Investigator. At the on-site study visits, subjects en-
rolling or agreeing to continue with the study will physically sign the IRB-approved informed con-
sent form. 
 
17.4 Patient insurance 
Ottobock has taken out patient insurance with Allianz Global Corporate & Specialty SE for all pa-
tients taking part in the trial under the policy number DEL007668190, NLL001051190 and 
ATL001224210. 
All investigators shall receive a copy of the insurance certificate and the insurance conditions; the 
latter must be known to the patients and made available on request.   
 

 
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7 
Project name 
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KAFO/SCO 
Project no. 
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18 Disclosure of data and publication policy 
The data generated in this study as well as the results of the study, are the property of the sponsor. 
The aim and contents of the clinical study, in addition to its results are to be treated as confidential 
by all persons involved in the clinical study.  
No publication, disclosure, or any other use of the results of this study are allowed without prior 
written permission of the sponsor. Any publication is based on the final report approved by Ot-
tobock. The investigator will receive a copy of the final report. Thereafter the manuscript for joint 
publication can be drafted. A joint publication of the results should be made in mutual agreement. 
All editorial decisions are taken jointly by Ottobock and the investigators. Ottobock is entitled to 
check a draft for publication latest 60 days before submission, and to advise within 60 days any nec-
essary reasonable supplements. 
Ottobock is entitled to utilize all relevant data of the study for registration purposes, worldwide sci-
entific product documentation and for publication.    
In case of a premature determination of the study, the publication strategy will be discussed and 
agreed between the sponsor and the investigators. Possibilities include i.e. to decide not to publish 
the study results.   
  
19 Retention of records 
Essential clinical investigation documents, as defined in ISO 14155-2020, are to be retained by the 
investigator during the clinical investigation and for the period required by the applicable regulatory 
requirements or for at least 15 years after the premature termination or completion of the clinical 
investigation, whichever is the longer. However, the investigator should contact the sponsor prior to 
destruction of any records or reports pertaining to the clinical investigation in order to ensure they 
no longer need to be retained. In addition, the sponsor should be contacted if the investigator plans 
to leave the site so that arrangements can be made for transfer of records. 
The medical files of study patients must be retained in accordance with local legislation and in ac-
cordance with the maximum period of time permitted by the hospital, institution or private practice.  
Sponsor and principal investigator shall take measures to prevent accidental or premature destruc-
tion of these documents. The principal investigator or sponsor may transfer custody of records to 
another person/party and document the transfer at the investigation site or at the sponsor's facility. 
 

 
CLINICAL  
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Project name 
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20 Study timeline  
First Patient first Visit planned: 1st Mar 2019. 
Last Patient last Visit planned: 31 Dec 2022 
 
Observational period per patient: 8 to 9 months depending which orthoses is used before cross-over 
Given the impact of the COVID-19 pandemic, the observational period per patient may increase by 
additional 6 to 7 months. 
Final report: 30 Jun 2023 
 
21 Publication Plan 
Please see section 18 for details regarding publication of study data. 

 
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22 References 
1 
Center for Disease Control and Prevention. National Health Interview Survey. Table 1a. Number of persons 
using assistive technology devices by age of person and anatomical device: United States, 1994. Accessed 
9/17/13 from http://www.cdc.gov/nchs/nhis/ad292tb1.htm 
(American publication was used to estimate patient numbers for Germany). 
2 
Hebert JS, Adrian BL, Eng P. Gait evaluation of an automatic stance-control knee orthosis in a patient with 
postpoliomyelitis. Arch Phys Med Rehabil. 2005;86:1676-1680. 
3 
Arazpour M, Bani MA, Hutchins SW, Jones RK. The physiological cost index of walking with mechanical 
and powered gait orthosis in patients with spinal cord injury. Spinal Cord. 2013;51:356-359 
4 
Davis PC, Bach TM, Pereira KM. The effect of stance control orthoses on gait characteristics and energy 
expenditure in knee-ankle-foot orthosis users. Prosthet Orthot Int. 2010;34:206-215. 
5 
Yakimovich T, Lemaire ED, Kofman J. Gait evaluation of a new electromechanical stance-control knee-
ankle-foot orthosis. Proceedings of the 28th IEEE EMBS Annual International Conference New York City, 
USA, Aug 30-Sept 3, 2006. Accessed on PubMed: PMID: 17946729 
6 
Yakimovich T, Lemaire ED, Kofman J, Eng P. Engineering design review of stance-control knee-ankle-foot 
orthoses. Journal of Rehab Res & Devel. 2009;46(2):257-268. 
7 
Sykes L, Ross ER, Powell ES, Edwards J. Objective measurement of use of the reciprocating gait orthosis 
(RGO) and the electrically augmented RGO in adult patients with spinal cord lesions. Prosthet Orthot Int. 
1996;20(3):182-190. 
8 
Berg KO, Wood-Dauphinee SL, Williams JI, Maki B. Measuring balance in the elderly: validation of an in-
strument. Can J Public Health. 1992 Jul-Aug;83 Suppl 2:S7-11. 
9 
Shumway-Cook A, Baldwin M, Polissar NL, Gruber W. Predicting the probability 
for falls in community-dwelling older adults. Phys Ther. 1997 Aug;77(8):812-9 
10 
Hafner BJ, Willingham LL, Buell NC, Allyn KJ, Smith DG. Evaluation of function, performance, and prefer-
ence as transfemoral amputees transition from mechanical to microprocessor control of the prosthetic knee. 
Arch Phys Med Rehabil. 2007;88:207–17. 
11 
Schwenk M, Lauenroth A, Stock C, Moreno RR, Oster P, McHugh G, Todd C, Hauer K. Definitions and 
methods of measuring and reporting on injurious falls in randomised controlled fall prevention trials: a sys-
tematic review. BMC Med Res Methodol. 2012 Apr 17;12:50. doi: 10.1186/1471-2288-12-50 . Review 
12 
Wood-Dauphinée SL, Opzoomer MA, Williams JI, Marchand B, Spitzer WO. Assess-ment of global func-
tion: The reintegration to normal living index. Arch Phys Med Re-habil 1988;69:583-90. 
13 
Stark SL, Edwards DF, Hollingsworth H, Gray DB. Validation of the reintegration to normal living index in a 
population of community-dwelling people with mobility limitations. Arch Phys Med Rehabil 2005;86:344-5. 
14 
Lerner D, Amick BC 3rd, Rogers WH, Malspeis S, Bungay K, Cynn D. The Work 
Limitations Questionnaire. Med Care. 2001 Jan;39(1):72-85. 
15 
Heinemann AW, Bode RK, O’Reilly C. Development and measurement properties of the Orthotics and Pros-
thetics Users’ Survey (OPUS): A comprehensive set of clinical outcome instruments. Prosthet Orthot Int. 
2003; 27:191-206. 
16 
Jones, Byron; Kenward, Michael G. (2015): Design and analysis of cross-over trials. 3. ed. Boca Raton, Fla.: 
CRC Press (Monographs on statistics & applied probability, 138). 
17 
Jennison, Christopher; Turnbull, Bruce W. (2000): Group sequential methods with applications to clinical 
trials. Boca Raton: Chapman & Hall/CRC 
 
 
 
 

 
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23 Appendix 
23.1 Appendix I: Procedure for device read-outs 
 
• Setup App 
A pdf-export of the Setup App will be taken by the CPO at definitive fitting, every time a change in 
the settings is done and at the follow-up visits. The file shall be stored according to the following 
convention: 
Exporting programming data from the C-Brace Setup-App  
1. Launch the C-Brace Setup-App 
2. Connect the mobile device and C-Brace via Bluetooth 
3. Go to the menu and select “Data overview” 
4. Choose the 
icon to export the data 
5. Use the following file name convention for the export file: 
 
CB2-XX-ZZ-DDMMMYY 
 
Where  
XX-ZZ is the Site ID and Patient ID and 
DDMMMYY is the programming date 
 
6. Download the data file and  upload the file to the eCRF. 
 

 
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Figure 5: Screenshot of the C-Brace Setup App 
 
• For C-Brace the following read – outs are collected from the SD-card of the joint unit at defini-
tive fitting as well as at follow – up visits 
 
• Steps with <1.5 km/h 
• Steps between 1.5 and 2.5 km/h 
• Steps between 2.5 and 3.5 km/h 
• Steps between 3.5 and 4.5 km/h 
• Steps between 4.5 and 5.5 km/h 
• Steps faster than5.5 km/h 
• Steps where the patient used stance phase flexion 
• How often did the patient sit down respectively activated the sitting function? 
• Time in stance/standing function 
• Time in sit function 
• Time in Freeze Mode 
• Time in Training Mode 

 
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• Time in User-Defined Mode (MyMode) 
• Time in Standby (C-Brace didn’t move for >60s) 
• Battery charging time 
• Total Time of use (counts basically every after the fitting minus time of power-off) 
 
 
 
• Step Count 
A step count transponder will be fixed on C-Brace and on KAFO/SCO. It will be read out after each 
observational period.  
 

 
CLINICAL  
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23.2 Appendix II: Study Overview (German) 
 
Sponsor 
Otto Bock Healthcare Products GmbH 
Studientitel kurz 
Klinische Studie zum Vergleich C-Brace vs. KAFO/SCO 
Studienziel 
Evaluierung der Effektivität und des Patientennutzens bei 
Patienten mit Beeinträchtigung der unteren Extremität 
hinsichtlich der Aktivitäten des täglichen Lebens im Vergleich 
zwischen C-Brace, einer Mikroprozessorgesteuerten Stand- und 
Schwungphasen-kontrollierten Orthese und der 
Alltagsversorgung, einer KAFO/SCO   
Design 
Prospektive, internationale, multizentrische, offene, 
kontrollierte, randomisierte cross-over Studie 
Prüfprodukte 
C-Brace, KAFOs, SCOs 
Primärer Wirksamkeits-
endpunkt 
Verbesserung der statischen und dynamischen Balance bei der 
Verwendung von C-Brace im Vergleich zu KAFO/SCO  
 
 
Sekundäre Endpunkte 
1. Evaluation des C-Brace Effekts auf das Gangbild, die 
Balance, das Gehen auf ebenem Untergrund, das Gehen 
während erschwerender Aufgaben, sowie während 
Aufmerksamkeitsaufgaben im Vergleich zu KAFO/SCO.  
2. Bestimmung und Vergleich der sicheren Anwendung von C-
Brace hinsichtlich der Parameter: Sturzhäufigkeit, Schwere 
der Stürze, Sturzassoziierte Verletzungen, Angst vor Stürzen 
und damit verbundener Behandlungsaufwand im Vergleich 
zu KAFO/SCO.  
3. Bestimmung der Sicherheit der Patienten bei der 
Durchführung verschiedener ambulanter Aktivitäten unter 
der Verwendung von C-Brace im Vergleich zu KAFO/SCO. 
4. Bestimmung der Lebensqualität und der Reintegration in 
normale Lebensumstände unter der Verwendung von C-
Brace im Vergleich zu KAFO/SCO. 

 
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5. Bestimmung des Umfangs der Behinderung und deren 
Einfluss auf die Produktivität. 
6. Bestimmung der Patientenzufriedenheit und der 
Verwendungsgewohnheit von C-Brace im Vergleich zu 
KAFO/SCO. 
7. Verringerte Sturzwahrscheinlichkeit bei der Verwendung 
von C-Brace im Vergleich zu KAFO /SCO 
 
Klinische Nachverfol-
gung 
Screening, Baseline 1 und 2, Visite 1 nach 3 Monaten 
Nutzungsdauer des ersten Prüfprodukts zu Hause, Visite 2 nach 
3 Monaten Nutzungsdauer des zweiten Prüfprodukts zu Hause  
Anzahl der Patienten 
56 
Einschlusskriterien 
• Patient wurde mit der Diagnostischen Testorthese (DTO) 
getestet und zeigte erfolgreich das Potential, C-Brace 
nutzen zu können 
• Patient hat einen BBS Wert < 45 
• Beeinträchtigung der unteren Extremität laut Indikation 
in der Gebrauchsanweisung  
• Vorangegangene aktive und verlässliche Nutzung einer 
unilateralen oder bilateralen Versorgung mit einer KAFO 
oder SCO in den letzten 3 Monaten vor Einschluss 
• Patient erfüllt die körperlichen Minimalvoraussetzungen 
für die C-Brace Versorgung, wie Muskelstatus, 
Gelenkmobilität, Beinachse und Kontrolle der Orthese 
• Der Nutzer erfüllt die körperlichen und geistigen 
Voraussetzungen, um optische, akustische Signale, 
sowie mechanische Vibrationen wahrzunehmen 
• Die bestehende Muskelkraft der Hüftflexoren und –
extensoren muss die Auslösung der Schwungphase 
ermöglichen (Kompensation durch Verwendung der 
Hüfte ist erlaubt) 
• Patient erklärt sich bereit, C-Brace für mindestens 1-2 

 
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Stunden pro Tag 5 Tage die Woche zu verwenden 
• Patient ist ≥18 Jahre alt 
• Patient ist fähig und willens, unabhängig sein 
Einverständnis zu geben 
• Person ist einverstanden, den Prozeduren innerhalb der 
klinischen Studie Folge zu leisten  
Ausschlusskriterien 
• Patient ist nicht in der Lage, alle Studienbesuche zu 
absolvieren oder ist unwillig/nicht in der Lage, den 
Anweisungen zu folgen 
• Patient war nicht in der Lage die DTO zu nutzen 
• Patient nutzt seine Orthese nicht für mindestens 1-2 
Stunden pro Tag an 5 Tagen pro Woche 
• Patient mit einem Körpergewicht > 125 kg 
(eingeschlossen Körpergewicht + schwerstes getragenes 
Objekt) 
• Patient mit Orthoprothese 
• Patient mit Flexionskontraktur im Knie- oder Hüftgelenk 
> 10° 
• Patient mit unkontrollierter moderater bis schwerer 
Spastizität (moderate Spastizität ist relative 
Kontraindikation) 
• Beinlängendifferenz > 15cm 
• Patient mit instabiler neurologischer, kardiovaskulärer 
oder pulmonaler Erkrankung oder Krebserkrankung 
• Schwangerschaft 
• Patient nutzt bereits C-Brace 
• Patient mit bekanntem Schwindel (Vertigo) oder 
Sturzhistorie, welche nicht in Bezug zur 
Orthesennutzung oder motorischer Behinderung steht 
• Patient ist nicht mit einer Orthese versorgt 
• Patient ist unfähig, selbständig an ihn ausgehändigte 

 
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Fragebögen zu beantworten; Patienten mit einer 
Beeinträchtigung der oberen Extremität dürfen verbal 
antworten 
• Patient nimmt während der geplanten Dauer der Studie 
an bereits einer weiteren klinischen Studie teil 
• Patient hat bereits an einer früheren C-Brace Studie 
teilgenommen 
Geplanter Zeitverlauf 
Geplante Studiendauer: 
First Patient In: 1 Mrz 2019 
 
Last Patient In: 30 Dec 2021 
Last Patient Out: 31 Mrz 2023  
Prüfleiter 
Zentrum 1: Prof. Frank Braatz 
Zentrum 2: Dr. Axel Ruetz  
Zentrum 3: Dr. Bea Hemmen 
Zentrum 4: PD Dr. Rüdiger Rupp 
Zentrum 5: Jason Wenig, CPO, FAAOP  
Zentrum 6: Tom DiBello, LO, CO, FAAOP 
Zentrum 7: Chris Toelle, LCO, ACM  
Zentrum 8: Eric Weber, LCPO, FAAOP 
Zentrum 9: Dr. Alexander Krebs 
  
Informationen 
zu 
zusätzlichen 
Prüfleitern 
in 
Addendum_CIPV5_SiteList_201217. 
 
Studienzentren 
Zentrum 1: Göttingen (D) 
Zentrum 2: Koblenz (D) 
Zentrum 3: Hoensbroek (NL) 
Zentrum 4: Heidelberg (D) 

 
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Project no. 
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Zentrum 5: Chicago, IL (USA) 
Zentrum 6: Houston, TX (USA) 
Zentrum 7: Sarasota, FL (USA) 
Zentrum 8: Seattle, WA (USA) 
Zentrum 9: Wien (AT) 
 
Informationen 
zu 
zusätzlichen 
Studienzentren 
in 
Addendum_CIPV5_SiteList_201217. 
 
Klinischer Projektman-
ager  
Dr. Marten Jakob 
 
 
 
 

 
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23.3 Appendix III: Example of the phone call protocol 
PHONE CALL 1 (1 Month) 
 
***THIS PHONE CALL HAS TO BE DONE IN THE END OF MONTH 1 AFTER ASSESSMENT OF READINESS!*** 
• 
Please remind the patient about the minimum time of use (1-2 hours, 5 days per week) of the current 
orthosis. 
• 
Ask the patient some questions about adverse events (AE) and device deficiencies (DD). 
• 
Remind the patient to call the investigator immediately in the case of malfunctions, falls or other limit-
ing events. 
• 
Remind the patient to document any falls and near falls as well as unexpected behavior of the 
current orthosis in the patient diary and to bring the diary at each visit. 
• 
If you need more space for your documentation please use page 8-9. 
 
Please specify the use of the current orthosis in day(s)/week and the hour(s)/day: 
 
Which orthosis (es) have you been using? (Check all that apply) 
|__|  C-Brace 
|__|  KAFO 
Time using the orthosis (es): 
|__|
 
day(s)/
week 
|__|
 
day(s)/
week 
|__|__|
 
hour(s)/
day 
|__|__|
 
hour(s)/
day 
Please specify, if the patient uses the current orthosis ≤ 1 hour/day  or < 5 days a week:   
 _______________________________________________________________________________________  
 _______________________________________________________________________________________  
 _______________________________________________________________________________________  
 
 
 
 
Did you have any health im-
pairments in the past 
|__| YES  
|__| NO 
If YES, number of 
events: 
|__|__|__| 

 
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month? 
 
 
Ask for adverse events (unto-
ward medical occurrence, un-
intended disease or injury, or 
untoward clinical sign wheth-
er or not related to the device) 
If YES, please specify: 
 
 
 
 
 
 
 
 
Please complete an Adverse Event CRF for each reported AE. 
Did your current orthosis 
have any malfunctions or 
other problems in the past 
month? 
Ask for device deficiencies 
|__| YES 
|__| NO 
If YES, number of 
events: 
|__|__|__| 
If YES, please specify: 
 
 
 
 
 
 
 
 
Please complete an Adverse Event CRF for each reported DD. 
 
Have you felt unstable in 
the past month? 
 
|__| Yes
 
 
 
|__| No 
 
Did your orthosis prevent 
any falls in the past 
month? 
|__| Yes
 
 
 
|__| No 
If YES:  
 
Number of events: 
|__|__| 
Did you have any falls in 
the past month? 
|__| Yes
 
 
 
|__| No 
If YES:  
 
Number of events: 
|__|__| 

 
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Did any falls require medi-
cal attention in the past 
month? 
|__| Yes
 
 
 
|__| No 
If YES:  
 
Number of events: 
|__|__| 
Did any falls cause perma-
nent injury in the past 
month? 
|__| Yes
 
 
 
|__| No 
If YES:  
 
Number of events: 
|__|__| 
Did any falls result in 
missed work in the past 
month? 
|__| Yes
 
 
 
|__| No 
If YES:  
 
Number of events: 
|__|__| 
 
 
Date of signature 
Name 
Signature 
|__|__| |__|__| | 2 | 0 | _ |    | 
  D  D    M  M     Y   Y   Y   Y