A Prospective, Multicentre, Randomised, Assessor Blinded Study Comparing the Efficacy, Including Patient Reported Outcomes of Two Different Daily gekoTM Treatment Durations in Conjunction With Standard Care, With Each Other and to Standard Care Alone, in Patients With Venous Leg Ulcers
Phase: NA
Conditions: Venous Leg Ulcer, Leg Ulcers Venous, Leg Ulcer, Wound Leg, Wound
Sponsor: Firstkind Ltd

                    
            
      Protocol # FSK-VLU- 004 
 
 
Version 12.2 
 
Date: 22May2020 
 
Confidential 
 
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A Prospective, Multicentre, Randomised, Assessor Blinded Study 
Comparing the Efficacy, including Patient Reported Outcomes of 
Two Different Daily gekoTM Treatment Durations in Conjunction 
with Standard Care, with each Other and to Standard Care Alone, in 
Patients with Venous Leg Ulcers. 
 
 
Protocol No.: FSK-VLU- 004 
Date: 22May2020 
Version: 12.2 
Investigational Product: gekoTM 
Indication: Venous leg ulcers  
Author:                           ________________________ 
 
 
 
Dr Eva-Lisa Heinrichs, MD 
 
 
 
Independent Medical Affairs Consultant 
          
            
                             SPONSOR 
 
 
 
 
Firstkind Ltd. 
Hawk House, Peregrine Business Park, Gomm Road 
High Wycombe, Buckinghamshire, HP13 7DL, UK 
 
Confidentiality Statement 
The information contained in this document is privileged and confidential may not be disclosed, except 
to the extent necessary to obtain informed consent and institutional approval to conduct the study, or as 
required by governmental authorities.  Persons to whom the information is disclosed must be informed 
that the information is confidential and may not be further disclosed by them. 
 
Firstkind Ltd 
 

                    
            
      Protocol # FSK-VLU- 004 
 
 
Version 12.2 
 
Date: 22May2020 
 
Confidential 
 
Page 2 of 93 
 
Firstkind Ltd., is a wholly own subsidiary of Sky Medical Technology Ltd., Daresbury 
Science and Innovations Campus, Keckwick Lane, Daresbury, Cheshire, WA4 4FS, UK 
Clinical Project Manager  
Marie-Therese Targett 
Clinical Project Manager 
Firstkind Ltd 
Hawk House, Peregrine Business Park 
Gomm Road, High Wycombe,  
Buckinghamshire, HP13 7DL, UK 
Tel: +44 (0) 7340903377 
E-mail: marie-therese.targett@firstkindmedical.com 
 
Clinical Affairs Manager  
Dr Kieron Day PhD 
Head of Clinical Affairs 
Firstkind Ltd 
Hawk House, Peregrine Business Park 
Gomm Road, High Wycombe,  
Buckinghamshire, HP13 7DL, UK 
Tel: +44 (0) 7921 106253 
E-mail: kieron.day@firstkindmedical.com 
 
SPONSOR SERIOUS ADVERSE EVENT (SAE) CONTACT  
Tel: +44 (0) 7340903377 
E-mail: safety@firstkindmedical.com 
 
 

Professor Keith Harding, CBE FRCGP FRCP FRCS 
5 June 2020 
Date 
 
Protocol # FSK-VLU- 004 
Version 12.2 
Date: 22May2020 
 
 
PROTOCOL APPROVAL SIGNATURES 
We, the undersigned, have reviewed this protocol and agree that it contains all relevant 
information required to meet GCP and all applicable regulatory guidelines and statutes. 
 
 
 
Rachel Fallon 
 
Rachel Fallon (Jun 8, 2020 16:43 GMT+1) 
Mrs Rachel Fallon 
Date 
Chief Technical Officer 
Firstkind Ltd 
Hawk House, Peregrine Business Park 
Gomm Road, High Wycombe, 
Buckinghamshire, HP13 7DL, UK 
 
 
05JUN2020 
Dr Kieron Day, PhD 
Date 
Head of Clinical Affairs 
Firstkind Ltd 
Hawk House, Peregrine Business Park 
Gomm Road, High Wycombe, 
Buckinghamshire, HP13 7DL, UK 
 
 
 
 
 
 
 
 
Lead Investigator 
WWIC Ltd 
Rhodfa Marics, Ynysmaerdy, 
Pontyclun, Rhondda Cynon Taf 
CF72 8UX, UK 
 
 
 
 
 
Confidential 
Page 3 of 93 

                    
            
      Protocol # FSK-VLU- 004 
 
 
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Confidential 
 
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INVESTIGATOR SIGNATURE PAGE 
I have read the protocol specified above and agree to participate in and comply with the 
procedures, as outlined herein for the conduct of this clinical study. I also agree to comply with 
the Investigational Review Board (IRB) requirements for testing on human patients. I agree to 
ensure that the requirements for obtaining informed consent are met. 
 
 
 
 
 
Investigator’s Signature 
 
 
 
 
Date 
Print Name 
 
 
 
 
 
 
Site Number 
 
 
 
 

Protocol Number FSK-VLU-004 
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Abbreviations 
 
ABPI  
Ankle-Brachial Pressure Index 
ADL 
 
Activities of Daily Living 
AE 
 
Adverse Event 
ANCOVA 
Analysis of Covariance  
BMI 
 
Body Mass Index 
CRF 
 
Case Report Form 
CRA 
 
Clinical Research Associate 
CTCAE 
Common Terminology Criteria for AEs 
CV 
 
Curriculum Vitae 
CWIS  
Cardiff Wound Impact Schedule 
DFU 
 
Diabetic Foot Ulcer 
DVT 
 
Deep Vein Thrombosis 
EOT 
 
End of Treatment 
ICF 
 
Informed Consent form 
IEC 
 
Institutional Ethics Committee 
ITT 
 
Intent-to-Treat 
FDA 
 
Food and Drug Administration 
GCP 
 
Good Clinical Practice 
GP 
 
General Practitioner 
HCV 
 
Healing Confirmation Visit 
ICH 
 
International Conference on Harmonisation 
ICMJE  
International Committee of Medical Journal Editors 
IRB 
 
Investigational Review Board 
LHR 
 
Linear Healing Rate 
MLU  
Mixed Leg Ulcer 
NA 
 
Non-adherent 
QoL 
 
Quality of Life 
PAR 
 
Percentage Area Reduction 

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PET 
 
Polyethylene Terephthalate 
PI 
 
Principal Investigator 
PP 
 
Per Protocol 
PWAT  
Photographic Wound Assessment Tool 
RV 
 
Run-in Visit 
SAE 
 
Serious Adverse Event 
SAP 
 
Statistical Analysis Plan 
SC 
 
Standard Care 
SOP 
 
Standard Operating Procedure 
TV 
 
Treatment Visit 
VAS 
 
Visual Analogue Scale 
VLU 
 
Venous Leg Ulcer 
 
 

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Synopsis 
Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
Title of Study: A Prospective, Multicentre, Randomised, Assessor Blinded Study Comparing the 
Efficacy, including Patient Reported Outcomes, of Two Different Daily geko™ Treatment Durations in 
Conjunction with Standard Care, with each Other and to Standard Care Alone, in Patients with Venous 
Leg Ulcers. 
Study Centre(s): Multinational, multicentre study with centres in the United Kingdom & Europe,  
Planned Number of Subjects:  
 
A total of 60 participants will be randomised in the study 
Indication for Use: Indicated for use as an adjunct to Standard Care (SC) in the treatment of Venous 
Leg Ulcers (VLUs) 
Objective: The objective of this study is to compare the efficacy of a daily geko™ device treatment 
duration of 12 hours, in conjunction with SC, to SC alone, in patients with venous leg ulcers.   
Endpoints: 
Primary Efficacy 
The primary efficacy endpoint is linear healing rate (LHR) of the study ulcer from first Treatment Phase 
visit (TV1) to the End of Treatment (EOT) as compared with LHR from first Run-in Phase visit (RV1) 
to TV1.  
 
EOT is defined as Treatment Phase visit 5 (TV5), withdrawal or that Treatment 
Phase visit at which 100% re-epithelialisation without drainage is first determined 
by the Principal Investigator (PI) or designee, whichever comes first. 
Each participant will be used as his/her own control.  
Wound area will be measured by a blinded independent wound expert using digital images taken at RV1, 
TV1 and at EOT.   
 
“Healing” of the study ulcer is determined by the PI or designee. “Healing” is defined as 100% re-
epithelialised without drainage as confirmed at the Healing Confirmation visit (HCV). 

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Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
Secondary Efficacy  
The overall secondary efficacy endpoints are:  
• Weekly LHR of the study ulcer measured by an independent blinded wound expert using digital images 
taken at each weekly visit until EOT. 
• Wound healing status at baseline and EOT assessed by an independent blinded wound expert using the 
Photographic Wound assessment Tool (PWAT) to evaluate digital images taken at RV1, TV1 and EOT 
and at HCV, if scheduled.  
• Incidence of healing at EOT, as determined by the by the PI or designee.   
The participant reported secondary efficacy endpoints are: 
• Time from TV1 to clinically significant pain reduction measured using a Visual Analogue Scale (VAS) 
instrument. For the purpose of this protocol a clinically significant reduction of pain is a mean reduction 
of ≥ 20.65 mm or a mean decrease of ≥ 10-20% in pain as measured on a 0-100 mm VAS. 
• Time from TV1 to first instance of no study ulcer pain measured using VAS. 
(No pain = < 5mm on VAS when VAS scores: 0-4 mm = no pain; 5-44 mm = mild pain; 45-74 mm = 
moderate pain; and 75-100 mm = severe pain) (1). 
• Pain score at EOT measured using VAS  
• Change from TV1 in Quality of Life (QoL) at EOT, assessed using the Cardiff Wound Impact Schedule 
(CWIS)  
• Change from TV1 in QoL at EOT, assessed using EQ-5D-5L  
 
Wound closure as reported by participants during the Follow-up Phase (FP1-FP3) 
Safety Assessments 
Safety will be assessed using the following parameters:  
• Incidence of AEs  
• Incidence of SAEs 
• Incidence of study ulcer infection 
• Incidence of study treatment related AEs (including gekoTM, compression bandaging and any dressings 
used to treat the study wound) 
• Incidence of investigational device (gekoTM) related AEs 
• Pain in the ulcer site (sudden onset of pain or increase in pain during the study Treatment Phase) 
 
Trial Design:  This study is designed as a prospective, multicentre, randomised, assessor blinded study 
designed to compare the efficacy, including participant reported outcomes, of a gekoTM treatment  in 

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Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
conjunction with SC, to SC alone, in the treatment of patients with VLUs. There are two arms in the 
study consisting of: 1) Participants randomised to receiving SC only; 2) Participants randomised to 
receiving SC and gekoTM 12 hours daily. 
A non adherent (NA) wound contact dressing and/or an absorbent dressing may be used if required, at 
the Investigator’s discretion in addition to SC. All dressing use and reason for dressing use will be 
recorded.  
 Multilayer, multicomponent compression therapy intended for the treatment of VLU based on local best 
practice will be used.  
The study will be a multinational, multicentre study with study centres in the UK & Europe  
The study will have a four-week Run-in Phase, a four-week Treatment Phase, 3 months Follow-up Phase 
and a Healing Confirmation visit (HCV) as applicable. 
At or up to 21 days before RV1, written informed consent from the participant will be obtained by the 
Investigator or suitably qualified designee before the performance of any protocol-specific procedure. 
 
Randomisation 
This is a multi-centre randomised study. Participants will be allocated to treatment groups using Adaptive 
Covariate Randomisation using an on-line randomisation tool.  
The randomisation will be applied centrally across the sites. 
Blinding 
The independent wound expert measuring the wound area and assessing the healing status of the wound 
will be blinded to the treatment assignments. 
The Run-in Phase (RV1 to RV5) is designed to determine each participant’s LHR when treated with 
SC alone. Participants will be seen and evaluated on a weekly basis. 
The Treatment Phase (TV1 to TV5)  

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Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
Participants will be seen and evaluated on a weekly basis. Efficacy evaluations each week will include 
Investigator assessment of wound healing and measurements of ulcer size using digital photos. Safety 
evaluations during the Treatment Phase will consist of adverse event assessments at each visit. 
The Follow-up Phase (FP1-FP3) 
Participants will be contacted at week 13, week 17 & week 21 to find out when their wound is healed.  
 
Healing Confirmation Visit (HCV) 
Participants whose ulcer presented with 100% re-epithelialisation without drainage as determined by the 
PI or designee will be scheduled for a Healing Confirmation Visit (HCV) in a minimum of 7 days time 
after which they will exit the study whether or not healing is confirmed. 
Duration of Treatment: The duration of the Treatment Phase is four weeks. 
Total Study Duration: The total study duration is a maximum of nine weeks: four weeks Run-in Phase 
and four weeks Treatment Phase followed by a HCV in a minimum of 7 days time if applicable. 
Participants who completed TV5 will have further 12 week Follow-up phase. 
 
Inclusion Criteria: Potential subjects are required to meet all of the following criteria for enrolment into 
the study and subsequent randomization.  
1. 
Male or female aged ≥ 18 years and able to provide written informed consent. 
2. 
Intact healthy skin at the site of geko™ device application. 
3. 
Patients who have a chronic venous leg ulcer determined to be due to underlying venous disease 
following evaluation in a multidisciplinary clinic setting or by a vascular surgeon, GP or Nurse 
specialist  
4.    A VLU of approximately ≥ 3cm2 and ≤ 39 cm2 at study enrolment i.e. Run In Phase Visit 1 (RV1). The 
largest ulcer within the given size range will be designated the study ulcer and the only one 
included in the study. If other ulcerations are present on the same leg they have to be more than 
2 cm apart if they are two separate wounds. . 
5. 
Study ulcer (current episode of ulceration in case of ulcer recurrence) has been present for at 
least 6 weeks but no more than 5 years prior to study entry.  
6. 
Ankle-Brachial Pressure Index (ABPI) of 0.75-1.24 inclusive measured at study entry or within 
8 weeks of study entry. 
7. 
No active index wound infection for a minimum of 48 hours prior to study entry (i.e. RV1). 
8. 
No systemic antimicrobial treatment for a minimum of seven days prior to study entry 
prescribed for index wound infection (i.e. RV1). 

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Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
9. 
Patient understands and is willing to participate in the study and is able to comply with study 
procedures and visits. 
 
Exclusion Criteria: Potential subjects meeting any of the following criteria will be excluded from 
enrolment and subsequent randomisation: 
1. Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, 
multicomponent compression therapy intended for the treatment of VLU. 
2. History of significant haematological disorders (e.g. Sickle Cell disease).  
3. History of Deep Vein Thrombosis (DVT) within six months preceding study entry  
4. History of Pyoderma Gangrenosum or other inflammatory ulceration. 
5. Pregnancy or breast feeding. 
6. Use of investigational drug or device within four weeks prior to study entry that may interfere 
with this study. 
7. Use of any neuro-modulation device. 
8. Surgery during three months prior to study entry (such as abdominal, gynaecological, hip or 
knee replacement)  
9. Trauma to the lower limbs that would prevent geko™ from stimulating the common peroneal 
nerve. 
10. No involuntary movement of the lower leg/foot at the maximum tolerable device setting. 
11. Any medication deemed by the Investigator to potentially interfere with the study treatment 
(e.g. systemic steroids). 
12. Participation in any other clinical study. 
 

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Name of Sponsor/Company: Firstkind Ltd, Hawk House, Peregrine Business Park, Gomm Road,  
High Wycombe, Buckinghamshire, HP13 7DL, UK 
Name of Study Product: gekoTM neuromuscular stimulator 
Comparator Product: Multilayer, multicomponent  compression therapy intended for the treatment of 
VLU (Standard Care) 
Protocol Number: FSK-VLU- 004 
 
Indication:  
Venous Leg Ulcers (VLUs) 
Statistical Analysis: 
Sample Size Determination and Rationale:  
The new sample size calculation is: 
Based on a pair-wise comparison of gekoTM 12h run-in vs treatment: 
From the interim data, there is a mean difference of 0.58 mm/week between run-in and treatment and a 
standard deviation of 0.97 mm/week.  
Assuming requirements of 80% power and p=0.05 (2-sided) 25 subjects would be needed in the gekoTM 
12H group. (30) 
Little benefit is foreseen in continuing the gekoTM 6h group, as statistical significance is not expected at 
the projected number of subjects in this trial.  
From the results of the Interim Analysis the new Treatment Groups are: 
Group 
Description 
SC 
Standard care (multilayer, multicomponent compression intended for the 
treatment of VLU) 
geko 12h 
gekoTM version XW, W-3 or variant (12 h daily neuro-stimulation) and SC 
 
Analysis Populations:  
The Intent-to-Treat (ITT) population is defined as the set of randomised participants who have at least 
one post-randomisation efficacy assessment for wound healing.  The ITT population will be the primary 
population for the analysis of primary and secondary endpoints.  
The Per Protocol (PP) population is defined as the set of participants who meet the ITT population 
requirements, defined above, and who were not associated with a major protocol violation/deviation.  
This population will be identified before the database lock. 
The Safety population is defined as the set of participants receiving treatment after randomisation. This 
population will be used for the analysis of safety parameters. 
Analysis Methods:  
A Statistical Analysis Plan (SAP) will be developed and approved before the database is locked. The 
SAP will present the detailed statistical methodology to be used in analysing the efficacy and safety data 
from this study. 

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TABLE OF CONTENTS 
 
Synopsis ........................................................................................................................... 7 
1. Introduction ................................................................................................................ 17 
1.1 The Problem .................................................................................................................... 17 
1.2 The Pathophysiology:  Venous Leg Ulceration ................................................................. 17 
1.3 The Treatment: Venous Leg Ulceration ........................................................................... 17 
1.4 geko™ neuromuscular stimulator .................................................................................... 18 
1.5 Summary of Prior Clinical Studies .................................................................................. 18 
2 Study Objective ............................................................................................................ 20 
2.1 Efficacy Endpoints ........................................................................................................... 20 
2.1.1 Primary Efficacy Endpoint .................................................................................................... 20 
2.1.2 Secondary Efficacy Endpoints ............................................................................................... 20 
2.1.3 Participant Reported Secondary Efficacy Endpoints ............................................................ 20 
2.2 Safety assessment ............................................................................................................. 21 
3 Study Design ................................................................................................................ 22 
3.1 Study Population ............................................................................................................. 23 
3.1.1 Number of Participants ........................................................................................................ 23 
3.1.2 Inclusion Criteria ................................................................................................................... 23 
3.1.3 Exclusion Criteria .................................................................................................................. 24 
4 Study Schedule ............................................................................................................ 26 
4.1 Run-in Phase .................................................................................................................... 26 
4.2 Treatment Phase .............................................................................................................. 28 
4.2.1 Treatment Visit 1 (TV1) – Prior to Randomization ............................................................... 28 
4.2.2 Treatment Visit 1 (TV1) – Randomisation and Post-randomisation .................................... 29 
4.2.3 Treatment Phase Visits 2- 4 (TV2 – TV4) .............................................................................. 29 
4.2.4 Final Treatment Phase Visit (TV5) ........................................................................................ 30 
4.3 Healing Confirmation ...................................................................................................... 32 
4.4 Follow-up Phase ............................................................................................................... 33 
4.5 Unscheduled Visits ........................................................................................................... 33 
4.6 Missed Visits .................................................................................................................... 34 
5 Participant Completion and Withdrawal ....................................................................... 35 
5.1 Participant Completion .................................................................................................... 35 
5.2 Premature Withdrawal / Discontinuation from the Study ................................................ 35 
5.3 Screen Failures ................................................................................................................ 36 
6 Study Treatments ......................................................................................................... 37 
6.1 Method for Assigning Eligible Patients to Treatment ....................................................... 37 
6.2 Description of the Investigational Device ......................................................................... 37 
6.3 Participant Investigational Device Use ............................................................................. 37 
6.4 Labelling .......................................................................................................................... 37 

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6.5 Device Storage, Handling, Application and Disposition ................................................... 37 
6.6 Product accountability ..................................................................................................... 38 
6.7 Participant Training and Instructions ............................................................................. 38 
7 Concomitant Medications ............................................................................................ 39 
8. Excluded Therapies ..................................................................................................... 40 
9 Description of Protocol Procedures and Assessments ................................................... 41 
9.1 Informed Consent ............................................................................................................ 41 
9.2 Assessment of Eligibility .................................................................................................. 41 
9.2.1 Re-Screening ......................................................................................................................... 41 
9.3 Demographics, Medical History, Study Ulcer History ...................................................... 41 
9.3.1 Demographics ....................................................................................................................... 41 
9.3.2 Medical History .................................................................................................................... 42 
9.3.3 Study Ulcer History ............................................................................................................... 42 
9.4 Quality of Life Assessment Questionnaire (CWIS and EQ-5D-5L) .................................. 43 
9.5 Physical Exam & Vital Signs ............................................................................................ 43 
9.5.1 Physical Examination ............................................................................................................ 43 
9.5.2 Vital Signs ............................................................................................................................. 43 
9.6 Ankle-Brachial Pressure Index (ABPI) ............................................................................ 44 
9.7 Pain Assessment Using Visual Analogue Scale (VAS) ...................................................... 44 
9.8 Assessment of the Compression Bandaging ...................................................................... 44 
9.9 Study Ulcer Leg and Ulcer Assessments ........................................................................... 45 
9.9.1 Venous Clinical Severity Score .............................................................................................. 45 
9.9.2 Leg Oedema Assessment (Study ulcer leg only) ................................................................... 45 
9.9.3 Study Ulcer Margin Assessment (Pre-debridement) ............................................................ 45 
9.9.4 Study Ulcer Bed Appearance (Pre-debridement) ................................................................. 46 
9.9.5 Study Ulcer Exudate Assessment ......................................................................................... 46 
9.9.6 Study Ulcer Surrounding Skin Assessment ........................................................................... 46 
9.9.7 Study Ulcer Infection Assessment ........................................................................................ 47 
9.9.8 Investigator Assessment of Study Ulcer Healing .................................................................. 47 
9.9.9 Study Ulcer Images ............................................................................................................... 47 
9.10 Recording of Device Usage ............................................................................................. 48 
10 Statistical Analysis ...................................................................................................... 49 
10.1 General Statistical Considerations ................................................................................. 49 
10.2 Sample Size Determination and Rationale ..................................................................... 49 
10.3 Randomisation ............................................................................................................... 49 
10.4 Blinding ......................................................................................................................... 49 
10.5 Interim Analysis for Sample Size Adjustment ................................................................ 49 
10.5.1 Procedure for Interim Analysis ........................................................................................... 50 
10.5.2 Results of Interim Analysis ................................................................................................. 51 
10.6 Treatment Groups ......................................................................................................... 51 
10.7 Description of Study Endpoints ...................................................................................... 51 
10.7.1 Primary Efficacy Endpoint .................................................................................................. 51 
10.7.2 Secondary Efficacy Endpoints ............................................................................................. 52 
10.7.3 Participant reported secondary efficacy endpoints ........................................................... 52 

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10.7.4 Safety Assessments ............................................................................................................ 52 
10.8 Participant Disposition ................................................................................................... 53 
10.9 Demographic and Baseline Characteristics .................................................................... 53 
10.10 Analysis Populations .................................................................................................... 53 
10.10.1 Intent to Treat Population ................................................................................................ 53 
10.10.2Per Protocol Population .................................................................................................... 53 
10.10.3 Safety population ............................................................................................................. 53 
10.11 Treatment Failures ....................................................................................................... 53 
10.12 Analysis Methods ......................................................................................................... 54 
10.12.1 Efficacy Analyses .............................................................................................................. 54 
10.12.2 Safety Analyses ................................................................................................................. 54 
10.12.2.1 Adverse Events .............................................................................................................. 54 
11 Adverse Events (Definitions and Reporting) ................................................................ 55 
11.1 Adverse Events............................................................................................................... 55 
11.2 Reporting and Follow-up of Adverse Events .................................................................. 55 
11.2.1 Impact on Study Treatment ............................................................................................... 55 
11.2.2 Intensity Assessment .......................................................................................................... 56 
11.2.3 Relatedness Assessment .................................................................................................... 56 
11.2.4 Treatment Given as a Result of the Event .......................................................................... 57 
11.2.5 Outcome Assessment ......................................................................................................... 57 
11.3 Serious Adverse Events .................................................................................................. 57 
11.4 Reporting of Serious Adverse Events ............................................................................. 57 
11.5 SAE Follow-up ............................................................................................................... 58 
12 Direct Access to Source Data/Documentation ............................................................. 59 
13 Quality Control and Quality Assurance ....................................................................... 60 
13.1 Monitoring Requirements .............................................................................................. 60 
13.2 Acceptability of Case Report Forms ............................................................................... 60 
13.3 Modification of Protocol ................................................................................................. 60 
13.4 Reporting Protocol Deviations ....................................................................................... 61 
14 Ethics and Regulatory Requirements .......................................................................... 62 
14.1 Institutional Review Board/Independent Ethics Committee ........................................... 62 
14.2 Investigator’s Responsibilities ........................................................................................ 62 
14.3 Participant Informed Consent Requirements ................................................................. 62 
15 Data Handling and Record Keeping ............................................................................. 64 
15.1 Recording and Collection of Data................................................................................... 64 
15.2 Clinical Data Management ............................................................................................. 64 
15.3 Archiving ....................................................................................................................... 64 
16 Publication Plan ......................................................................................................... 66 
17. References ................................................................................................................ 69 
18 APPENDICES ............................................................................................................... 71 
Appendix 1: Instructions for Use and Fitting Instructions geko™ Devices ............................ 71 
Appendix 2: Photographic Wound Assessment Tool (PWAT) ............................................... 72 

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Appendix 3: Venous Ulcer Clinical Severity Score ................................................................ 73 
Appendix 4:  EQ-5D-5L Questionnaire ................................................................................. 75 
Appendix 5: Cardiff Wound Impact Schedule (CWIS) .......................................................... 77 
Appendix 6: Participant Diary .............................................................................................. 84 
Appendix 7: Protocol Amendments ....................................................................................... 86 
Appendix 8: Sub-study to the VLU efficacy study at selected clinical sites to determine 
whether oedema prevents neuromuscular stimulation by the geko™ device in a sub-set of VLU 
patients. ................................................................................................................................. 89 
 
 
 
 

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1. Introduction 
1.1 The Problem 
Leg ulcers pose a significant burden on patients and health providers. In approximately 50-
60% of cases, the aetiology is venous insufficiency (2) in which event they are referred to as 
venous leg ulcerations (VLUs) (3; 4). Older age, obesity, previous leg injuries, deep venous 
thrombosis, and phlebitis are the key risk factors (5). VLUs usually require weeks or months 
to heal and not uncommonly wound care specialists see patients who have suffered for years. 
In addition, VLUs are often recurrent (6; 7). 
Ulcer pain is a common characteristic of VLUs and has a significant negative impact on 
patients’ quality of life. A study by Phillips in 1994 found that 65% of patients with VLU 
complained of severe pain and 68% of patients stated that their ulcer had a negative emotional 
and psychological impact on them including feelings of fear, social isolation, anger, 
depression, anxiety and negative self-image (8). 
1.2 The Pathophysiology:  Venous Leg Ulceration 
The venous ulcer pathophysiology is not entirely clear. Primary mechanisms for ulcer 
formation such as venous incompetence and associated venous hypertension have been 
described. Elongation of capillaries, micro-thrombosis, fibrin cuffs around vessels and 
leukocyte leakage are pathological microvascular changes seen with and attributed to venous 
hypertension (9).   
The venous system of the lower extremity consists of superficial and deep veins connected by 
perforating veins.  Normally, valves within the veins ensure the direction of blood flow from 
the superficial into the deep venous system and back to the heart.  Pumping action of the 
musculature of the lower extremities aids the deep venous flow during physical activity.  
Factors such as immobility; ineffective pumping of the calf muscle; and venous valve 
dysfunction from trauma, congenital absence, venous thrombosis, or phlebitis may lead to 
venous incompetence (10; 11). Subsequent, chronic venous stasis causes pooling of blood in 
the venous circulatory system which in turn triggers further capillary damage and activation of 
inflammatory process. Leukocyte activation, endothelial damage, platelet aggregation, and 
intracellular oedema have been shown to contribute to VLU development and impaired wound 
healing (10) Oedema of the lower extremities followed by hyper-pigmentation, venous stasis 
dermatitis, hemosiderin deposits, loss of hair, thicken nails, atrophie blanche and 
lipodermatosclerosis, are all typical findings in patients with longstanding venous 
insufficiency.  
 
1.3 The Treatment: Venous Leg Ulceration 
Addressing oedema and improving the microcirculation in the skin is key in order to treat 
venous ulceration. Reduction of the oedema is best achieved using compression bandages and 
healing rates in venous leg ulcers are significantly improved by the application of compression 
therapy (12). High level compression (40 mmHg at the ankle) is more effective at healing 
venous leg ulcers than low compression (13). High level compression should only be applied 

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in the absence of significant arterial disease.  The threshold normally employed for the use of 
high level compression is an ankle brachial pressure index (ABPI) of 0.8. Normal adult values 
range between 0.9 and 1.2.  Levels lower than 0.8 indicate presence of arterial disease.  
High level compression can be achieved using a variety of bandaging systems or compression 
hosiery. However, generally only approximately 45% of patients treated with optimal 
compression therapy (14) will heal within 12 weeks.  
Hypoxia is a key factor that limits wound healing (15). Anything that negatively affects the 
delivery of oxygen to tissues, such as poor vascularisation, will interfere with healing and the 
link between compromised circulation and ulceration has been well established and well 
described (16). Thus an adjunct therapy which increases blood flow, circulation and/or delivery 
of oxygen could be a valuable aid in healing of VLUs. 
1.4 geko™ neuromuscular stimulator 
The geko™ device, manufactured by Firstkind Ltd (High Wycombe, United Kingdom), is a 
small disposable, battery powered, neuromuscular stimulation device designed to enhance 
blood flow in the lower limbs and improve healing of leg ulcers as an adjunct to standard care. 
It is made from mylar (polyethylene terephthalate (PET)) and is enclosed in a polypropylene 
casing. It is self-adhesive with a hydrogel layer that will stick it to the skin. geko™ is applied 
externally to the leg on the outer/posterior aspect of the knee. This positioning enables integral 
electrodes to apply a stimulus to the common peroneal nerve. These nerves control the 
contraction of a complex of muscles in the lower leg. 
The stimulation of these nerves by the geko™ device causes the muscles to contract 
isometrically and will not affect normal movement of the limb nor patient mobility. Contraction 
of the lower leg muscles will boost venous return, local blood circulation and help prevent 
venous thrombosis. The geko™ device has ten stimulation levels to balance maximal effect of 
stimulation with patient comfort. The optimal stimulation level, which may vary between 
patients, is achieved when a stimulus results in a dorsi-flexion of the foot.   
The geko™ device is fully insulated by a protective moulding and there is no risk of shock. It 
has charge-balanced waveforms that yield no build-up of charge in the patient. Therefore, 
provided the device is used in accordance with the instructions for use galvanic effects such as 
electrical burns cannot occur. The device is powered by battery, and is thus totally isolated from 
the mains electricity supply. The primary lithium coin cell battery powering the device is 
removable for disposal. 
 
1.5 Summary of Prior Clinical Studies 
The gekoTM has been tested clinically to evaluate its safety and efficacy in human use. These 
studies did not give rise to any safety concerns for gekoTM. 
Increases in venous, arterial and microcirculatory volume flow in the lower limb has been 
demonstrated in healthy volunteers. Venous flow was shown to increase by up to 100% (17; 
18; 19), arterial flow by up to 75% (19) and microcirculatory by up to 400% (17; 19; 20) 21) 

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The gekoTM has also been shown in a series of case studies to increase the rate of healing in 
venous leg ulcers, and it has been shown to be safe to use as a medical device. There were 
reports of skin irritations in these case studies. These types of adverse reactions are however 
anticipated in patients with venous leg ulcers as a result of increased sensitivity due to 
compromised blood circulation and metabolism in the skin.  
Skin irritation has been shown to be more likely in patients who wear the device in excess of 
the recommended use. One study followed 12 patients with 18 heard to heal or none healing 
VLUs and showed a change in healing rate from 0.06% per week at baseline to 9.35% per week 
whilst using the gekoTM. Over the course of the study, 44% of wounds healed and 39% 
decreased in size (20). 
Another series of case studies looked into the therapeutic effect of the gekoTM device on wound 
healing outcomes over an eight-week period. Thirty patients with non-healing wounds (> 3-
month duration) of either VLU, mixed aetiology leg ulcer (MLU) or diabetic foot ulcer (DFU) 
aetiology were recruited from a local outpatient wound clinic in the South Wales area. During 
the eight-week period two participants (8%) achieved complete re-epithelialisation between 
baseline and end of study. The mean wound surface area decreased over time (7.6 cm2) and an 
increase of 21% in the mean percentage of granulation tissue was observed in the wound bed. 
Pain levels reduced in 52% of patients who completed the study. The Investigators concluded 
that their findings support the use of gekoTM in patients with painful VLUs and MLUs (21). 
1.6 Study Rationale, Benefits and Risks 
This study is designed to evaluate the efficacy of two gekoTM daily treatment durations in 
conjunction with Standard Care (SC), consisting of multilayer, multicomponent compression 
therapy intended for the treatment of VLU, compared with each other and to that of SC alone 
in participants with VLUs. gekoTM has been shown to facilitate wound healing in earlier studies 
(See Section 1.5 Summary of prior clinical studies) and patients receiving the gekoTM 6h or 12h 
daily in addition to SC may experience faster wound healing as well as greater pain reduction 
than patients treated with SC alone. We believe that treatment with gekoTM will in conjunction 
with SC potentially lead to faster healing and re-epithelialisation than treatment with SC alone 
for patients with VLU.  
A potential risk for participants randomised to the gekoTM daily treatments is the possibility of 
eczema at the application site. This, however, is unlikely based on previous experience with 
gekoTM (20). Potential adverse events for all research participants in this study are intrinsic to 
the nature of VLUs, including but not limited to: pain and infection at the wound site, and 
maceration of the surrounding skin. 
Not all patients may respond to the geko TM stimulus. Therefore, patients with no involuntary 
movement of the lower leg/foot at the maximum tolerable device setting will be excluded from 
the study. 
 
 

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2 Study Objective  
The objective of this study is to compare the efficacy of a daily geko™ device treatment 
durations of 12 hours, in conjunction with SC, to SC alone, in patients with venous leg ulcers.  
2.1 Efficacy Endpoints 
2.1.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is linear healing rate (LHR) from TV1 to EOT as compared 
with LHR from RV1 to TV1. LHR will be calculated by linear regression of the 4 
measurements in each phase, with linear wound edge advance being based on the change with 
respect to time of wound area divided by perimeter, according to Vidal’s method (22) [Each 
participant will be used as his/her own control, i.e. a participant’s healing trajectory before 
introduction of treatment will be compared to his/her healing trajectory after introduction of 
treatment. Wound area and perimeter will be measured by a blinded independent wound 
expert using digital images taken at baseline (RV1), first treatment visit (TV1) and at EOT.  
 
2.1.2 Secondary Efficacy Endpoints 
The secondary efficacy endpoints are:  
• 
Weekly LHR measured by an independent blinded wound expert using digital images 
taken at each weekly visit until TV5, withdrawal or healing whichever comes sooner. 
• 
Wound healing status at baseline and EOT assessed by an independent blinded wound 
expert using PWAT to evaluate digital images taken at RV1, TV1 and at withdrawal, healing 
or at the end of the Treatment Phase (TV5), whichever comes sooner.  
• 
Incidence of healing at EOT, as determined by the Investigator  
“Healing” of the study ulcer is determined by the PI or designee. “Healing” is defined as 
100% re-epithelialised without drainage as confirmed at the Healing Confirmation visit 
(HCV). 
 
2.1.3 Participant Reported Secondary Efficacy Endpoints 
The participant reported secondary efficacy endpoints are: 
Time from TV1 to clinically significant pain reduction measured using a Visual Analogue 
Scale (VAS) instrument. For the purpose of this protocol a clinically significant reduction of 
pain is a mean reduction of ≥ 20.65 mm or a mean decrease of ≥ 10-20% in pain as measured 
on a 0-100 mm VAS (23; 24).  
 
Time from TV1 to first instance of no study ulcer pain measured using VAS. 
(No pain = < 5mm on VAS when VAS scores: 0-4 mm = no pain; 5-44 mm = mild pain; 45-
74 mm = moderate pain; and 75-100 mm = severe pain) (1). 

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Pain score at EOT measured using VAS  
 
Change from TV1 in Quality of Life (QoL) at EOT, assessed using the Cardiff Wound Impact 
Schedule (CWIS)  
Change from TV1 in QoL at EOT, assessed using EQ-5D-5L  
Wound closure as reported by participants during the Follow-up Phase (FP1-FP3) 
 
The two QoL instruments, the CWIS a wound specific QoL instrument, and the EQ-5D-5L, a 
standardised instrument for measuring generic health status, will be provided to the 
participants for completion at RV1, TV1 and at EOT. In case of withdrawal all attempts 
should be made to obtain final QOL assessments. 
 
2.2 Safety assessment 
Safety will be assessed based on incidence of adverse events (AEs), incidence of serious AEs 
(SAEs), incidence of study treatment related AEs, incidence of investigational device related 
AEs,  ulcer infection, and incidence of pain in the ulcer site (sudden onset of pain or increase 
in pain during the study treatment). 

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3 Study Design 
This study is designed as a prospective, multicentre, randomised, assessor blinded study 
designed to compare the efficacy including participant reported outcomes of two different 
gekoTM treatment durations in conjunction with SC, with each other and with SC alone, in the 
treatment of patients with venous leg ulcers. There will therefore be two arms in the study 
consisting of: 1) participants randomised to receiving SC only; 2) participants randomised to 
receiving SC, and gekoTM 12 hours daily. 
The standard care therapy in this study is multilayer, multicomponent compression therapy 
intended for the treatment of VLU. A non-adherent (NA) wound contact dressing and/or an 
absorbent dressing may be used if required, at the Investigator’s discretion in addition to SC. 
All dressing use and reason for dressing use will be recorded.  
Multiple multilayer, multicomponent compression bandaging systems delivering levels of  
compression and with clinical data to support their use are commercially available. The 
compression bandaging system of choice based on local best practice will be used. Moreover, 
this will prevent any problems around consistency of method of application of compression.  
The study will be a multinational, multicentre study with study centres in the UK and Europe 
The study will have three phases: a four-week Run-in Phase, a four-week Treatment Phase 
and a twelve-week follow-up phase.  A schematic picture of the study flow is provided below 
in Figure 1. 
 
Figure 1: Study Schedule 
At or up to 21 days before the first Run-in Phase Visit (RV1), the Investigator or suitably 
qualified designee will, prior to the performance of any protocol-specific procedure, obtain 
written informed consent from the patient.  
Run-in Phase
4 weeks of  SC
Randomi
sation
Treatment 
Phase
4 weeks of :
1) SC; 
or
2) gekoTM 12h    
daily + SC
Follow-up 
Phase
Follow up on
Week 13
Week 17
Week 21

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During the Run-in Phase participants will be evaluated on a weekly basis. Efficacy 
evaluations each week will include Investigator assessment of wound healing and 
measurements of ulcer size using digital images. For the purpose of this study, healing is 
defined as 100% re-epithelialisation without drainage confirmed at the Healing Confirmation 
visit (HCV). The compression bandaging system of choice based on local best practice in the 
study centre in question will be used.  
The results of the four-week Run-in Phase during which only SC will be used as treatment, 
will provide an SC only healing trajectory (LHR curve) (22) for each of the participants and 
each participant will serve as his/her own control.  
At RV1, the Investigator will assess and confirm the patient’s eligibility and select the study 
ulcer.  Each participant will have only one VLU selected as the study ulcer.  In the situation 
where a participant has more than one VLU at the RV1 visit, the Investigator will select the 
largest VLU that meets the eligibility criteria of the protocol as the study ulcer. If other 
ulcerations are present on the same leg they should be more than 2 cm apart from the study 
ulcer. 
At the first Treatment Phase visit (TV1), once the Investigator has confirmed the participant’s 
continued eligibility, randomisation and assignment to study treatment will take place.  
The total maximum study duration is nine weeks, followed up by twelve weeks Follow-up 
Phase. All participants remaining in the study at the final Treatment Phase visit, TV5, will 
complete study visits unless they present with 100% re-epithelialisation without drainage as 
determined by the PI or designee, in which case they will be scheduled for a Healing 
Confirmation Visit (HCV) in a minimum of 7 days. All participants attending a HCV will 
complete study visits at this visit regardless if healing is confirmed or not.  
 
3.1 Study Population 
3.1.1 Number of Participants 
A total of 60 patients will be randomised into the study 
3.1.2 Inclusion Criteria 
The inclusion criteria of the study are: 
1. Male or female aged ≥ 18 years and able to provide written informed consent. 
 
2. Intact healthy skin at the site of gekoTM device application. 
 
3. Patients who have a chronic venous leg ulcer determined to be due to underlying 
venous disease following evaluation in a multidisciplinary clinic setting or by a 
vascular surgeon, GP or Nurse specialist. 
 
4.  A VLU of approximately  ≥ 3cm2 and ≤ 39 cm2 at study enrolment i.e. Run In Phase 
Visit 1 (RV1). The largest ulcer within the given size range will be designated the study 

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ulcer and the only one included in the study. If other ulcerations are present on the same 
leg they have to be more than 2 cm apart if they are separate wounds.  
 
5. Study ulcer (current episode of ulceration in case of ulcer recurrence) has been present 
for at least 6 weeks but no more than 5 years prior to study entry.  
 
6. Ankle-Brachial Pressure Index (ABPI) of 0.75-1.24 inclusive measured at study entry 
or within 8 weeks of study entry 
 
7. No active index wound infection for a minimum of 48 hours prior to study entry (i.e. 
RV1). 
 
8. No systemic antimicrobial treatment for a minimum of seven days prior to study entry 
prescribed for index wound infection (i.e. RV1). 
 
9. Patient understands and is willing to participate in the study and is able to comply with 
study procedures and visits. 
 
3.1.3 Exclusion Criteria 
The exclusion criteria of the study are: 
1. Known allergy to any of the protocol-stipulated treatments, or non-tolerance of multilayer, 
multicomponent compression therapy intended for the treatment of VLU. 
2. History of significant haematological disorders (e.g. Sickle Cell disease).  
3. History of Deep Vein Thrombosis (DVT) within six months preceding study entry (i.e. 
RV1). 
4. History of Pyoderma Gangrenosum or other inflammatory ulceration. 
5. Pregnancy or breast feeding. 
6. Use of investigational drug or device within four weeks prior to study entry (i.e. RV1) 
that may interfere with this study. 
7. Use of any neuro-modulation device. 
8. Surgery during three months preceding study entry (such as abdominal, gynaecological, 
hip or knee replacement) (i.e. RV1).   
9. Trauma to the lower limbs that would prevent geko™ from stimulating the common 
peroneal nerve. 
10. No involuntary movement of the lower leg/foot at the maximum tolerable device 
setting. 
11. Any medication deemed by the Investigator to potentially interfere with the study 
treatment (e.g. systemic steroids.) 

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12. Participation in any other clinical study. 

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4 Study Schedule 
The study is divided into three phases: the Run-in Phase, the Treatment Phase and Follow-up 
Phase. The schedules for the protocol-specified assessments and procedures in each phase are 
detailed below in the following sections. 
One week equals 7 days and the allowed visit window is one week ± 3 days. Every attempt 
should be made to maintain participants on their original weekly treatment schedule. When 
determining the visit dates, the reference should always be to the RV1 or TV1 date and not the 
participant’s previous visit. 
There will be a Healing Confirmation Visit (HCV) scheduled in a minimum 7 days for 
participants who present with 100% re-epithelialisation without drainage of the study ulcer as 
determined by the PI or designee during the Treatment Phase. 
4.1 Run-in Phase 
Investigators should confirm that the patient has provided written informed consent. Thereafter 
procedures during the Run-in Phase should be performed in the following order: 
 
Confirm Participant response to gekoTM treatment by presence of involuntary 
movement of the lower leg/foot at the maximum tolerable device setting (RV1 only). 
 
Measure ABPI if a valid ABPI reading has not taken within 8 weeks of RV1 
 
Confirm eligibility (RV1 only). If the patient is not eligible, discharge the patient from 
the study as a screen failure. If the patient is eligible continue with the following 
procedures:  
 Record medical history and study ulcer history (RV1 only). 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s 
primary language (RV1 only). 
 Perform physical examination and assess Body Mass Index (BMI) (RV1 only). 
 Assess concomitant medications (Con Med) and update Con Med page in case 
report form [CRF] as appropriate). 
 Assess compression bandaging (See Section 9.8). 
 Record study ulcer location, history and duration (RV1 only).  
Note: ‘Study ulcer location’ is defined by the ulcer being on the left or right leg, 
by the location of the ulcer on the malleolus, low gaiter or high calf, and by the 
positioning of the ulcer as lateral, medial, anterior or posterior. 
 Administer the study ulcer pain VAS assessment.  
 Determine Venous Clinical Severity Score (RV1 only) 
 Assess for AEs. . Any AEs occurring during the Run In Phase are to be recorded 
on an AE form  
 Cleanse the study ulcer. 
 Obtain a digital image of the study ulcer (if debridement is planned, this is the 
Pre-debridement image). N.B., all study ulcer measurements will be performed 
using the pre-debridement images.  

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 At the discretion of the Investigator, perform debridement of the study ulcer to 
obtain a clean, granulating ulcer base with minimal adherent slough.  
 If applicable, obtain a post-debridement digital image of the study ulcer  
 Apply SC.  A non-adherent (NA) wound contact dressing and/or an absorbent 
dressing may be used at Investigator’s discretion if required in addition to the 
compression system.  
 Record all dressing use 
 Assess for any post-application AEs 
 Schedule the next study visit in one week’s time 
The Run-in Phase ends with TV1 which is also the first visit of the Treatment Phase. 
 
 

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Table 1: Schedule of Events – Run-in Phase 
Activity/Assessment 
RV1 
RV2 
RV3 
RV4 
RV5/TV1 
Informed consent 
√ 
 
 
 
 
Assessment of response to geko TM  
treatment 
√∞ 
 
 
 
 
Ankle-Brachial Index (ABPI) if a 
valid ABPI reading has not been 
taken within 8  weeks of RV1 
√ 
 
 
 
 
Confirmation of eligibility 
√ 
 
 
 
 
Medical history  
√ 
 
 
 
 
CWIS, EQ-5D-5L and assessments 
√ 
 
 
 
 
Physical examination and BMI 
√ 
 
 
 
 
Concomitant medications 
√ 
√ 
√ 
√ 
√ 
Assessment of compression 
bandaging 
√ 
√ 
√ 
√ 
√ 
Study ulcer history 
√ 
 
 
 
 
Study ulcer pain (VAS) assessment  
√ 
√ 
√ 
√ 
√ 
Venous Clinical Severity Score 
√ 
 
 
 
√ 
Assess for AEs 
 
√ 
√ 
√ 
√ 
Study ulcer cleaning 
√ 
√ 
√ 
√ 
√ 
Study ulcer surrounding skin 
assessment 
√ 
 
 
 
 
Study ulcer image(s) 
√⌘ 
√⌘ 
√⌘ 
√⌘ 
√⌘ 
Study ulcer debridement 
√§ 
√§ 
√§ 
√§ 
√§ 
Application of compression 
√¶ 
√¶ 
√¶ 
√¶ 
√¶ 
Assessment for post application AEs 
√ 
√ 
√ 
√ 
√ 
Scheduling of next visit  
√ 
√ 
√ 
√ 
√ 
∞ Presence of involuntary movement of the lower leg/foot at the maximum tolerable device setting 
§ Study ulcer debridement at Investigator’s discretion. N.B. All study ulcer measurements will be performed using the pre-debridement 
images. 
⌘ If debridement is performed a pre-debridement and a post-debridement image is taken.  
¶ A non adherent (NA) wound contact dressing and/or an absorbent dressing may be used at Investigator’s discretion if required in addition 
to the compression system. 
 
4.2 Treatment Phase 
4.2.1 Treatment Visit 1 (TV1) – Prior to Randomization 
The assessments on TV1 should be performed in the following order: 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary 
language. 
 Administer the study ulcer pain VAS assessment. 

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 Check for any changes in the participant’s health. Any AEs during TV1 prior to 
randomisation are recorded in the participant’s medical history. Following 
randomisation and during TV2-TV5, update the AE or Serious Adverse Events (SAE) 
CRF pages as applicable. 
 Assess concomitant medications. 
 Assess compression bandaging (See Section 9.8) 
 Clean the study ulcer. 
 Obtain a digital image of the study ulcer (if debridement is planned, this is the Pre-
debridement image). N.B. All study ulcer measurements will be performed using the 
pre-debridement images. 
 At the discretion of the Investigator, debride the study ulcer to obtain a clean, 
granulating ulcer base with minimal adherent slough.  
 If applicable, obtain a post-debridement digital image of the study ulcer.  
 Verify the participant’s continued eligibility (See Sections 3.1.2 and 3.1.3). 
If the participant is not eligible, discharge the participant from the study as a screen failure. 
If a patient initially fails to meet inclusion/exclusion criteria he/she may later be reconsidered 
for participation, in which case the patient will be re-consented and assigned a new screening 
number at the time of re-screening. Patients who fail their first screening attempt may be re-
screened once (i.e., up to two screenings) and be enrolled if they meet ALL inclusion and NO 
exclusion criteria at the second screening visit. 
If the patient is eligible, perform the following procedures immediately 
4.2.2 Treatment Visit 1 (TV1) – Randomisation and Post-randomisation 
Perform the activities below in the following order: 
 Randomise the participant. At the randomisation visit, the study ulcer needs to be   ≥ 2 cm2 
and ≤ 30 cm2. If other ulcerations are present on the same leg, they need to be at least 2cm 
away from the study ulcer 
 Apply SC.  
 Apply appropriate gekoTM to those participants randomised to either gekoTM group. 
 Assess for any post-application AE. 
 Provide the participant with gekoTM devices as applicable in accordance with the 
randomisation outcome 
 Schedule the next study visit in one week’s time.  
NB. Each gekoTM device can only be used twice. 
4.2.3 Treatment Phase Visits 2- 4 (TV2 – TV4) 
Perform the assessments/activities in the following order: 
 Administer the study ulcer pain VAS assessment. 
 Check for any changes in the participant’s health and update the AE or Serious Adverse 
Events (SAE) CRF pages if applicable. 
 Assess concomitant medications.  

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 Assess compression bandaging (See Section 9.8). 
 Assess study ulcer healing (to be performed by treating PI or designee) 
If the study ulcer is 100% re-epithelialised without drainage: 
 Obtain a digital image of the study ulcer site. 
 Provide appropriate follow-up therapy for the healed ulcer and schedule the participant for a 
Healing Confirmation Visit (HCV) in a minimum of 7 days. 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary language. 
 Complete the remaining applicable visit procedures. 
If the study ulcer is not 100% re-epithelialised without drainage: 
 Clean the study ulcer. 
 Check for signs of clinical infection. If clinical diagnosis of infection has been made, the 
participant should be treated with topical antimicrobials or oral antibiotics in accordance 
with local best practice. SC, or SC plus either gekoTM treatment will continue at 
Investigator’s discretion. 
 Obtain a digital image of the study ulcer (if debridement is planned this will be the pre-
debridement image). N.B. All study ulcer measurements will be performed using the pre-
debridement images. 
 Debride  the study ulcer to obtain a clean, granulating ulcer base with minimal adherent 
slough, at the discretion of the Investigator.  
 If applicable, obtain a digital image of the study ulcer (post-debridement image) 
 Apply appropriate gekoTM to those participants randomised to either gekoTM group. 
 Assess for any post-application Aes. 
 Schedule the next study visit in one week’s time. 
Note that TV4 is the final scheduled study product application.  
 Apply SC. A non adherent (NA) wound contact dressing and/or an absorbent dressing may 
be used at Investigator’s discretion if required in addition to SC. All dressing use will be 
recorded. 
 Assess and sign the participant diary card (gekoTM groups only). 
 
4.2.4 Final Treatment Phase Visit (TV5) 
Perform the assessments/activities in the following order: 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary language 
 Administer the study ulcer pain VAS assessment. 
 Assess and sign the participant diary card (gekoTM groups only). 
 Check for any changes in the participant’s health and update the AE or SAE CRF pages if 
applicable. 
 Assess concomitant medications. 
 Assess compression bandaging (See Section 9.8). 
 Assess study ulcer healing (to be performed by treating PI or designee) 

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If the study ulcer is 100% re-epithelialised without drainage: 
 Obtain a digital image of the study ulcer site.  
 Provide appropriate follow-up therapy for the healed ulcer and schedule the participant for a 
Healing Confirmation Visit (HCV) in a minimum of 7 days. 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary language. 
 Complete the remaining applicable visit procedures.  
If the study ulcer is NOT 100% re-epithelialised without drainage: 
 Complete the remaining visit procedures. 
 Check for signs of clinical infection. 
 Clean the study ulcer. 
 Digital image of the study ulcer (if debridement is planned this will be the pre-debridement 
image). N.B., all study ulcer measurements will be performed using the pre-debridement 
images. 
 Debride the study ulcer to obtain a clean, granulating ulcer base with minimal adherent 
slough, at the discretion of the Investigator.  
 If applicable, obtain a digital image of the study ulcer (post-debridement).  
 Provide appropriate follow-up therapy for the non-healed ulcer and exit the participant from 
the study. 
 
 
 

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Table 2: Schedule of Events – Treatment Phase 
 
 
4.3 Healing Confirmation  
Only those subjects whose study ulcer is 100% re-epithelialised without drainage as 
determined by the PI or designee during a TV, will be scheduled for a Healing Confirmation 
Visit (HCV). The HCV is to be scheduled a minimum of 7 days after the first determination 
of re-epithelialisation. 
During the HCV perform the activities in the following order:  
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary language. 
Activity/Assessment 
TV1 (pre-
rand) 
TV1 (post 
rand) 
 
TV2 
 
TV3 
 
TV4 
 
TV5 /Final 
Visit 
 
CWIS and EQ-5D-5L assessments 
√ 
 
 
 
 
√ 
Study ulcer pain assessment (VAS) 
√ 
 
√ 
√ 
√ 
√ 
Assess for AEs  
√ 
 
√ 
√ 
√ 
√ 
Assess concomitant medications 
√ 
 
√ 
√ 
√ 
√ 
Assess compression bandaging 
√ 
 
√ 
√ 
√ 
√ 
Study ulcer exudate assessment 
√ 
 
√ 
√ 
√ 
√ 
Venous Clinical Severity Score 
 
 
 
 
 
√ 
Leg oedema assessment 
√ 
 
√ 
√ 
√ 
√ 
Study ulcer healing assessment 
 
 
√∞ 
√∞ 
√∞ 
√∞ 
Study ulcer cleaning 
√ 
 
√ 
√ 
√ 
√ 
Study ulcer margin assessment 
√ 
 
√ 
√ 
√ 
√ 
Study ulcer surrounding skin assessment 
√ 
 
√ 
√ 
√ 
√ 
Study ulcer bed appearance 
√ 
 
√ 
√ 
√ 
√ 
Signs of infection of study ulcer 
√¶ 
 
√¶ 
√¶ 
√¶ 
√ 
Study ulcer image(s)  
√⌘ 
 
√⌘ 
√⌘ 
√⌘ 
√⌘ 
Study ulcer debridement 
√§ 
 
√§ 
√§ 
√§ 
√§ 
Confirm eligibility 
√ 
 
 
 
 
 
Randomisation 
 
√ 
 
 
 
 
Apply SC 
 
√ 
√ 
√ 
√ 
√ 
Apply geko TM as per randomisation 
 
√ 
√ 
√ 
√ 
 
Assess for post-application AEs 
 
√ 
√ 
√ 
√ 
√ 
Assess and sign the participant diary card (geko 
groups only) 
 
 
√ 
√ 
√ 
√ 
Provide the participant with the appropriate 
geko devices as applicable 
 
√ 
√ 
√ 
√ 
 
Schedule next visit 
 
√ 
√ 
√ 
√ 
 
∞ Study ulcer healing assessment to be performed by PI or designee. Participants with 100% re-epithelialisation without 
drainage will be scheduled for a Healing Confirmation Visit in a minimum of 7 days time. 
¶ If clinical diagnosis of infection has been made, the participant should be treated with topical antimicrobials or oral 
antibiotics in accordance with local best practice. Study treatment will continue as per Investigator’s discretion  
⌘ If debridement is performed a pre-debridement and a post-debridement image is taken. N.B. All study ulcer 
measurements will be performed using the pre-debridement images. 
§ Study ulcer debridement at Investigator’s discretion 

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 Administer the study ulcer pain VAS assessment. 
 Check for any changes in the participant’s health and update the AE or SAE CRF pages if 
applicable. 
 Assess concomitant medications. 
 Assess compression bandaging (See Section 9.8).  
 Assess study ulcer healing (to be performed by treating PI or designee). 
If the study ulcer remains 100% re-epithelialised without drainage: 
 Obtain a digital image of the study ulcer site. 
 Provide appropriate follow-up therapy for the participant and the healed ulcer and exit the 
participant from the study. 
 Complete the remaining applicable visit (TV5) procedures.  
If the study ulcer remains 100% re-epithelialised without drainage at the HCV, the date of 
healing for the purpose of study results will be the date 100% re-epithelialisation without 
drainage was first determined by the PI or designee. 
 
If the study ulcer is NOT 100% re-epithelialised without drainage: 
 Complete the remaining visit (TV5) procedures. 
 Check for signs of clinical infection. 
 Clean the study ulcer. 
 Obtain a digital image of the study ulcer.  
 Provide appropriate follow-up therapy for the participant and the non-healed ulcer and exit 
the participant from the study.  
 
4.4 Follow-up Phase 
Participants who completed TV5 will be contacted after 4, 8 & 12 weeks to find out the status 
of the study wound. 
At week 13, 17 and 21; a member of the research team (at the clinical site) will contact the 
patient to find out  
 
whether the wound is healed or not healed 
 if healed (the date wound was healed) 
4.5 Unscheduled Visits 
Unscheduled visits may be required in addition to the visits detailed above.  Additional visits 
are at the discretion of the Investigator.  An example of an unscheduled visit is when a change 
of compression bandaging is required between scheduled visits.  The details of these 
unscheduled visits with participants will be recorded in the medical records/source documents 
and on the CRF. 
 
 

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4.6 Missed Visits 
If a participant misses a visit, the site is to make every effort to have the participant return as 
soon as possible to make up the visit.  Once the participant is seen, he/she is to return to his/her 
original weekly visit schedule.  For example, if a participant was seen regularly on Mondays 
but missed a scheduled Monday visit and came in on Wednesday, he/she should return the next 
Monday to maintain his/her weekly Monday visit schedule 
 

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5 Participant Completion and Withdrawal 
5.1 Participant Completion 
A participant whose study ulcer has healed will be considered as having completed the study. 
For the purpose of this study healing is defined as 100% re-epithelialisation with no drainage 
as determined by the PI or designee. The 100% re-epithelialisation and absence of drainage 
must be confirmed at a subsequent clinic visit (HCV) in a minimum of 7 days (See Section 
4.3). If 100% re-epithelialisation of the study ulcer with no drainage is confirmed at the HCV, 
the date of healing will be the date the ulcer was first determined by the PI or designee as 
100% re-epithelialised and without drainage.  
5.2 Premature Withdrawal / Discontinuation from the Study 
A participant who is randomised and has completed TV1 of the Treatment Phase but who 
does not complete the study, as defined in Section 5.1, has prematurely discontinued. 
All participants have the right to withdraw at any point during the study without prejudice to 
his/her treatment. It will be documented whether or not a participant completed the clinical 
study. If for any participant, study treatment or observations were discontinued, the reason(s) 
will be recorded.  
The Investigator can discontinue a participant at any time if it is considered medically 
necessary.  
In addition, participants will be withdrawn from the study, at the Investigator’s discretion, if 
any of the following occur: 
A participant is significantly non-compliant with the requirements of the protocol.  
A participant has revascularisation surgery on the leg with the study ulcer. 
The study ulcer cannot be compressed. 
The study ulcer merges with an adjacent ulcer.   
The reason for treatment discontinuation or withdrawal from the study will be recorded in the 
source documents and on the appropriate page of the CRF. Every attempt should be made to 
complete the relevant CRF pages. 
Before a participant is identified as lost-to-follow up, the site should make all reasonable 
efforts to contact the participant. These attempts must be documented and should include at a 
minimum one phone call and one letter/email.  
Participants who meet the criteria for premature withdrawal during the Treatment Phase will 
have TV5 assessments performed.   
In the event that a participant is prematurely discontinued from the study at any time due to an AE or 
SAE, the procedures stated in Section 5.2 must be followed. 
 

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5.3 Screen Failures 
A patient who has signed a consent form, has been assigned a screening number, but is not 
randomised is classified as a screen failure.  Patient number, demography and reason for 
screen failure will be collected. 

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6 Study Treatments 
6.1 Method for Assigning Eligible Patients to Treatment 
Eligible patients will be assigned to one of the following three treatment groups, based on the 
randomisation schedule:  
 Group 1: SC only (multilayer, multicomponent compression intended for the treatment of 
VLU) 
 Group 2: 12 hours daily treatment with gekoTM (XW, W-3 or variant) plus SC (multilayer, 
multicomponent compression intended for the treatment of VLU) 
 
6.2 Description of the Investigational Device 
The gekoTM device is CE marked (GB12/87339; SGS, United Kingdom Ltd). The geko™ 
device is made from mylar (polyethylene terephthalate (PET)), it is enclosed in a polypropylene 
casing and a hydrogel layer will stick it to the skin. In this study the XW, W-3 or variant will 
be used. (Refer to Appendix 1. for Fitting Instructions). 
 
6.3 Participant Investigational Device Use  
 
Each gekoTM device can be used only twice. Participants randomised to the gekoTM 12 hour 
daily treatment groups will at each visit be provided with a sufficient number of gekoTM devices 
to last until the next scheduled Treatment Phase visit. Participants should ensure that they 
always have enough devices to carry them through to the next scheduled Treatment Phase visit. 
Participants randomised to either gekoTM group will be provided with a diary card on which 
their gekoTM usage will be recorded. The participants should bring the diary card with them at 
each site visit at which the cards will be verified and signed. 
6.4 Labelling 
The study supplies will be labelled in accordance with all applicable regulatory requirements.  
Each investigator will be supplied with sufficient supplies to conduct the study. 
Each gekoTM device will have a number which will be unique to the particular device.  The 
unique device number will be recorded in the participant diary each time it is used to provide a 
check that the allocated treatment has been provided. At each study visit the study device usage 
will be assessed and new devices provided. 
 
6.5 Device Storage, Handling, Application and Disposition 
The investigational devices will be supplied in single use labelled packages. 
The whole device with the battery in place can be disposed of in domestic waste.   

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Details on application of the geko™ device and Instructions for Use are available in Appendix 
1. 
6.6 Product accountability 
The Investigator or designee will verify the contents of each shipment against the shipping 
documents. Verification of investigational device receipt will be documented according to 
Sponsor’s requirements. 
An accountability log will be provided to the site for use by the Investigator to maintain current 
and accurate inventory records (batch, expiry, and quantity) covering the dispensing and the 
destruction of the investigational product.  
At the conclusion of the study the Investigator must agree to return all investigational products 
as instructed by Sponsor.   
6.7 Participant Training and Instructions 
Participants randomised to either gekoTM group will be trained in the use of the gekoTM device 
and be provided with Instructions for Use.  Such participants will also be instructed to hand in 
the above mentioned diary card at each study visit for verification and signature by the 
Investigator. 
All participants will be instructed to ring or visit the study site if there is any issue with the 
compression bandaging such as, but not limited to, pain, discomfort, and removal or soiling of 
the bandage. 
All participants will be instructed to contact the Investigator if signs or symptoms of infection 
develop prior to their next scheduled visit. 

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7 Concomitant Medications  
All medications and therapies administered or taken by the participant throughout the study 
will be recorded in the source documents and on the appropriate page of the Case Report Form 
(CRF). 
For each medication the following will be documented: 
 Medication/treatment name (generic name may be used if trade name is unknown) 
 Dose, unit, and frequency of dosing (individual dosages, not total daily dose). Note:  Each 
new dose of medication should be recorded as a separate entry, with the exception of 
medications that are given on a sliding scale. For these, it is acceptable to enter the range of 
the dosage, including the start and stop dates for which the specified dosage range was used. 
 Route of dosing 
 Indication for use 
 The start date  
 The stop date (if applicable) 
 

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8. Excluded Therapies 
The following treatments are prohibited throughout the study:  
 Any neuro-modulation device 
 Any other investigational treatment/medications 
 

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9 Description of Protocol Procedures and Assessments 
9.1 Informed Consent 
The Investigator or suitably qualified designee will obtain written informed consent for this 
study from all participants before the performance of any protocol-specific procedure.  
In obtaining and documenting informed consent the Investigator must comply with applicable 
regulatory requirements and must adhere to Good Clinical Practice (GCP).  The Investigator, 
or designee, must fully inform patients of all pertinent aspects of the study.  Before written 
informed consent may be obtained, the Investigator, or a person designated by the Investigator, 
must provide the patient ample time and opportunity to inquire about details of the study and 
to decide whether or not to participate in the study.  All questions about the study must be 
answered to the satisfaction of the patient.  Prior to the patient taking part in the study, the 
written informed consent must be signed and personally dated by the patient and by the person 
who conducted the informed consent discussion.   
The signed informed consent must remain in the patient's files and be available for verification 
by the study monitor.  The patient's medical record should clearly indicate that the patient is 
participating in this study. 
9.2 Assessment of Eligibility 
At the RV1 and TV1, the Investigator must assess a patient’s continued suitability and 
eligibility for the study, especially with regards to the Inclusion and Exclusion criteria of this 
Protocol described in Sections 3.1.2 and 3.1.3.  If a patient is not suitable or eligible for the 
study then the patient will be a screen failure.   
 
9.2.1 Re-Screening 
 
If a patient fails to meet inclusion/exclusion criteria and is later reconsidered for participation, 
the patient will be re-consented and assigned a new screening number at the time of re-
screening. Patients who fail their first screening attempt may be re-screened once again (i.e., 
up to two screenings per patient) and may be enrolled if they are found to meet all inclusion 
and no exclusion criteria at the screening visit. 
  
9.3 Demographics, Medical History, Study Ulcer History 
9.3.1 Demographics 
 
For the purposes of this study, demographic information will include: 
 Dates of Informed Consent Form signature  
   Date of birth 
 Gender 

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 Use of tobacco products 
 
9.3.2 Medical History 
 
A medical history will be recorded at RV1 and will include: 
• 
All ongoing medical conditions 
• 
All previously resolved medical conditions related to Venous Insufficiency or Leg 
Ulceration or which are relevant in the opinion of the Investigator  
Medical histories will be recorded using the body system categories outlined below: 
• 
Cardiovascular 
• 
Lymphatic 
• 
Respiratory 
• 
Hematologic 
• 
Gastrointestinal 
• 
Immunologic 
• 
Renal 
• 
Dermatologic 
• 
Hepatic
• 
Psychiatric
• 
Neurological 
• 
Genitourinary 
• 
Endocrine 
• 
Other 
 
For each relevant history, the following will be documented:   
• 
Disease/disorder/condition 
• 
Year of diagnosis 
• 
History status (resolved or ongoing) 
 
9.3.3 Study Ulcer History 
 Duration of the current study ulcer 
Note: ‘Duration’ is defined as the length of time that the study ulcer has been open at 
this location (since the last time it was fully closed if the ulcer in question is a recurrent 
ulcer).   
 Current compression bandaging system used for the study ulcer and length of time that this 
has been used 
 Prior treatments that have been used on the study ulcer 
 Age when the participant developed his/her first ulcer  
 Total number of previous ulcers 
 Location of the current study ulcer 
Note: ‘Study ulcer location’ is defined by the ulcer being on the left or right leg, by the 
location of the ulcer on the malleolus, low gaiter or high calf, and by the positioning of 
the ulcer as lateral, medial, anterior or posterior. 

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 Number of additional leg ulcers and location of each present at the screening visits 
 History of VLU recurrence 
Note: ‘Recurrence’ is defined as the re-opening of an ulcer after healing. 
 History of a DVT (deep vein thrombosis) in the study leg 
 
9.4 Quality of Life Assessment Questionnaire (CWIS and EQ-5D-5L) 
The Cardiff Wound Impact Schedule, CWIS, will be used to assess the “disease specific” QoL. 
A generic QoL questionnaire, the EQ-5D-5L questionnaire, will be used to assess the effects 
of treatments on the participants’ QoL. Results may be used to derive a patient-reported 
outcome useful for health-related QoL claims on the investigational device treatment.  
The questionnaires (and instructions for completing them) will be provided to all participants 
at the first Run-in Phase visit (RV1) and at TV1 prior to the application of randomised 
treatment. The questionnaires will also be provided and collected upon EOT, as part of the End 
of Study procedures.  
The QoL assessments will be performed prior to any other study procedures, when scheduled, 
to minimise bias. 
 
9.5 Physical Exam & Vital Signs 
 
9.5.1 Physical Examination 
The physical examination will be performed at study entry (RV1) and will include routine 
examinations for the following: 
 Abnormalities of the extremities 
 Neurologic abnormalities 
 Heart/cardiovascular abnormalities 
 Musculoskeletal abnormalities 
 Dermatologic abnormalities 
 Any other body system for which an abnormality is noted and which, in the opinion of the 
Investigator, is relevant to the safety of the participant or could impact safety or efficacy 
results for the participant; i.e. the abnormality is clinically significant.  
Each abnormality will be recorded and the Investigator will record an assessment of its clinical 
significance.    
 
9.5.2 Vital Signs 
The following vital signs will be collected at study entry (RV1):    
 Height  

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 Weight  
 BMI (derived from the height and weight measurements)  
 
9.6 Ankle-Brachial Pressure Index (ABPI) 
Ankle Brachial Pressure Index (ABPI) is the ratio of blood pressure measured at the ankle to 
that measured at the arm.  An ABPI < 0.8 indicates that there is a high probability that arterial 
insufficiency is present (positive predictive value 95% and negative predictive value 99%) in a 
general practice population). Compression therapy may be safely applied to patients with an 
ABPI >0.8 in addition to a comprehensive medical history. 
If upon clinical examination the patient exhibits signs or symptoms that could suggest 
peripheral arterial disease, further investigations to determine vascular status may be warranted. 
ABPI must be completed prior to any other study related procedures at the first Run-in Phase 
visit (RV1) unless a valid ABPI measurement has been taken within 8 weeks of the RV1 taking 
palce.   
 
9.7 Pain Assessment Using Visual Analogue Scale (VAS) 
Pain intensity of the VLU is to be assessed before any dressing changes or other wound 
manipulations at all study visits (Run-in Phase and Treatment Phase).  
The Visual Analogue Scale (VAS) is a commonly used pain assessment tool suitable for the 
purpose of this study. Participants will be using the VAS instrument to record study ulcer pain. 
They will be asked to mark the point that best represented the pain intensity at the ulcer site on 
a horizontal line (100mm in length) anchored by word descriptors at each end, as "no pain" on 
the left side and "worst pain possible" on the right side of the line. Importantly, the participant 
marks on the line or by pointing to a position on the line the point that he/she feels represents 
his/her perception of his/her current state. The VAS score is determined by measuring in 
millimetres from the left hand end of the line to the point indicated by the participant. 
 
9.8 Assessment of the Compression Bandaging 
The following questions will be asked to assess the compression bandaging during the Run-in 
and Treatment Phase visits: 
1. 
Whether the bandage was in place at each visit (Yes/No) 
2. 
If the bandage was not in place, the date it was removed and the reason for removal 
(slippage, strikethrough or other) 
3. 
If the bandage is in place but needs to be changed at an unscheduled visit, the reason 
for removal/change must be recorded from the following:  
a. 
Maximum wear time 

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b. 
Participant withdrawn 
c. 
AE 
d. 
Slippage 
e. 
Dressing change needed with details of dressing in question 
f. 
Soiled 
g. 
Participant request 
h. 
Other 
9.9 Study Ulcer Leg and Ulcer Assessments 
The following assessments of the study ulcer/ study ulcer leg will be conducted as specified 
below. 
9.9.1 Venous Clinical Severity Score 
The Venous Clinical Severity Score (25) will be obtained only at the RV1, RV5 visit and at the 
last study visit. See Appendix 3 for details regarding scoring. 
 
9.9.2 Leg Oedema Assessment (Study ulcer leg only) 
The study ulcer leg oedema will be assessed during the study visits using a modification of the 
Guelph General Hospital Congestive Heart Failure Pathway leg oedema scale (26).  
 
Leg Oedema Scale 
 
No 
 
1+ : Mild pitting, slight indentation, no perceptible swelling of the leg 
 
2+ : Moderate pitting, indentation subsides rapidly 
 
3+ : Deep pitting, indentation remains for a short time, leg looks swollen 
 
4+ : Very deep pitting, indentation lasts a long time, leg is very swollen 
 
9.9.3 Study Ulcer Margin Assessment (Pre-debridement) 
The study ulcer margins will be assessed during study treatment visits and the presence/absence 
of the following features will be recorded (27): 
 Granulating   
 Epithelialising  
 Sloping 
 
 Rolled  
 Punched out  

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 Everted 
 Purple             
 Undermining 
 Sinus  
 Inflamed  
 
9.9.4 Study Ulcer Bed Appearance (Pre-debridement)  
The study ulcer bed appearance will be assessed during study treatment visits and the following 
features will be recorded:  
 Percentage granulation tissue 
 Quality of granulation tissue 
 Percentage non-viable tissue 
 
9.9.5 Study Ulcer Exudate Assessment 
The Investigator will determine the amount and type, if any, of study ulcer exudate. In 
determining the amount of study ulcer exudate the Investigator should take into account the 
amount of exudate absorbed into the study ulcer dressing. The following categories will be used 
to quantify the amount of study ulcer exudate: 
 No exudate 
 Minimal amount 
 Moderate amount 
 Heavy/large/copious amounts 
 
9.9.6 Study Ulcer Surrounding Skin Assessment 
The study ulcer surrounding tissue within 4 cm of the ulcer edge will be assessed and 
presence/absence of the following features will be recorded: 
 Tissue paper skin          
 Peri-ulcer oedema        
 Eczema                
 Maceration                     
 Dry/scaly skin            
 Erythema                       
 Healthy skin             
 Inflammation  
 Pustules 
 Rash 
 Skin abnormalities such as scarring                

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9.9.7 Study Ulcer Infection Assessment 
The presence/absence of infection at the study ulcer site will be documented at each study visit. 
All participants who show evidence of an ulcer infection during the Treatment Phase must have 
the infection reported on an AE CRF. Any AEs during Run-in Phase are recorded in the 
participant’s medical history.  
The determination of presence/absence of ulcer infection will be made by the Investigator. The 
participant should be treated with topical antimicrobials or oral antibiotics in accordance with 
local best practice. SC, or SC plus gekoTM treatment will continue at Investigator’s discretion 
during the Treatment Phase. Antibiotic interventions will be recorded on the Concomitant 
Medications Form and the event will be categorised as an AE, serious if it meets the definition 
of that category.   
All participants will be instructed to contact the Investigator if signs or symptoms of infection 
develop prior to their next scheduled visit. 
During an episode of infection, any modification of compression treatment is at the discretion 
of the Investigator and will be recorded in the CRF.   
 
9.9.8 Investigator Assessment of Study Ulcer Healing 
“Healing” is defined as 100% re-epithelialised without drainage determined by the PI or 
designee as confirmed at the Healing Confirmation visit (HCV).  This means that in order to 
be considered as “healed”, the study ulcer will need to remain closed without drainage for a 
minimum of 7 days from the date when it is first determined to be 100% re-epithelialised 
without drainage.   
At each TV visit and at the HCV if scheduled, the PI or designee will assess the wound by 
answering the following questions: 
 Is the study ulcer 100% re-epithelialised? 
 Is there any drainage present? 
When the Questions are asked at a TV visit, if question 1 is answered “yes” and question 2 is 
answered “no”, the patient is scheduled for a Healing Confirmation Visit (HCV) in a minimum 
of 7 days. During the HCV questions 1 and 2 above are repeated. Question 1 must be answered 
“yes” and Question 2 must be answered “no” at the HCV for the study ulcer to be considered 
healed.  
“If Question 1 is answered “yes “and Question 2 is answered “no”, the date of healing will be 
the date the 100% re-epithelialisation without drainage was first determined by the PI or 
designee. 
9.9.9 Study Ulcer Images 
The study ulcer will be digitally photographed according to the schedules in this protocol using 
the Aranz SilhouetteStarTM, a digital camera which is part of the SilhouetteTM system. 

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SilhouetteStarTM is a portable, non-contact device for imaging and measuring ulcers.  This 
system will be used to measure the study ulcer area and to assess the study ulcer appearance.  
Run-in Phase and Treatment Phase images of the study ulcer will be taken at each weekly visit, 
as well  as at the HCV, if scheduled, will be used to measure and document ulcer size and 
healing status.  
If debridement is performed, both pre and post-debridement images will be taken.  The pre-
debridement measurement will serve as the basis for all wound area related endpoints in this 
study.  
All SilhouetteStarTM users must have training in the used system prior to undertaking any 
imaging and/or measurements for this study. A separate imaging and measurement manual with 
more detail about SilhouetteStarTM will be provided in the Operations Manual for the study. 
If the index ulcer during the course of healing splits into a number of smaller wounds, the area’s 
of the resulting wounds will be combined and used for analysis. 
At end of study all images will be sent to an independent blinded wound expert for wound area 
measurements. The wound area measurements will be used for all PAR related analysis. 
 
9.10 Recording of Device Usage 
The participants randomised to the gekoTMstudy group will be provided with a participant diary 
for the purpose to record the daily gekoTM device usage. 
 

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10 Statistical Analysis 
 
10.1 General Statistical Considerations 
This section presents general information concerning the statistical analyses which will be 
performed in this study, including for example, information about sample size, interim analysis, 
randomisation, treatment groups, endpoints, and the analysis methods and statistical tests to be 
performed.  Detailed information on these and other related matters will be provided in the 
study Statistical Analysis Plan (SAP), as a separate document. 
10.2 Sample Size Determination and Rationale 
The sample size calculation is based on pilot data pooled from 2 two sources (The Canadian 
Bandaging Trial (28), and case series) and gives an estimate of effect size (delta/standard 
deviation) ranging from 0.80 to 1.1. In this design, each group is internally controlled by a four-
week baseline, allowing pair-wise intra-group comparison, and normalised inter-group 
comparison. Assuming the more conservative figure for effect size, and assuming 50% effect 
size for the reduced dosage group, n=35 per group yields 90% power to establish an effect for 
gekoTM at the lower dosage. 
Because of the short study duration, the discontinuation rate is predicted to be about at most 
20%.  To accommodate the potential discontinuations, the trial proposes to randomise 126 
subjects (42 per treatment group). 
10.3 Randomisation 
This is a multi-centre randomised clinical study. Participants will be allocated to treatment 
groups using Adaptive Covariate Randomisation using an on-line randomisation tool (29).  
The randomisation will be applied centrally across the sites.  
10.4 Blinding 
The independent wound expert measuring the wound area will receive the wound images 
without participant identification data or study visit data and he/she will therefore be blinded 
when measuring the wound area and assessing the healing status of the wound. 
10.5 Interim Analysis for Sample Size Adjustment  
An interim analysis will be conducted when approximately 60% have been enrolled. 
The Interim Analysis will be directed and conducted by an independent statistician who is not 
involved in the study conduct other than the Interim Analysis. The main purpose of this Interim 
Analysis is to validate the assumptions in calculating the sample size (i.e., the effect sizes 
assumed in the initial sample size calculations). Using the observed difference of percentage 
reduction in area, and all other original assumptions noted above, the independent statistician 
will re-calculate the sample size. Based on the documented sample size re-calculation and the 
observed drop-out rate, the independent statistician’s report will either recommend a new, 
increased sample size sufficient to achieve the study’s objectives or will provide documentation 
that the current sample size is sufficient with no need to increase the sample size. 

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10.5.1 Procedure for Interim Analysis 
The data to be used in the interim analysis and the treatment assignment of each randomised 
subject will be given to the statistician. Using this data, the independent statistician will 
calculate the following metrics for the primary end point:  
1.  
Mean and standard deviation of LHR in each group. 
2. 
The dropout rate at the time of the Interim Analysis, IA 
3. 
The statistical power of the trial at the time of the IA (using a conditional power 
approach).  
a. 
If the statistical power is larger than 50%, then the sample size will be adjusted 
upward and no Type I error rate adjustment will be made to the final analysis. 
b. 
If the statistical power is less than 50%, the Type I error rate will be inflated and 
statistical adjustment will be made to the final analysis if the decision to increase 
the sample size is made. That is, the observed p-value, as well as the point 
estimate of the response rates, and the 95% CIs will be based on: 
p-value =2*{1- T2(n1+n2 - 1) (|z1 + z2|/√2)},  
Healing rate for each treatment group: Ŝ = (√n1 ×Ŝ1  + √n2 ×Ŝ2)/(√n1 + √n2),  
95% Confidence Intervals= (Ŝ -2 tα/2:2(n1+n2 - 1)σ, Ŝ +2 tα/2:2(n1+n2 - 1)σ) 
where n1, is the sample size in the treatment group before interim analysis and 
n2 is the sample size in treatment group after the interim analysis; T2(n1+n2 - 
1) ( . ) is t distribution with 2 (n1+ n2-1) degrees of freedom.  The Ŝ1 is the 
healing rate of the n1 observation before the interim analysis and Ŝ2 is the 
healing rate of the n2 observation after the interim analysis. The (√n1 + √n2)σ 
is the observed pooled standard deviation before and after the interim analysis.  
4. 
Using the observed metrics above, along with Type I Error Rate of 0.05, the sample size 
will be re-calculated and the independent statistician will provide the following to the 
sponsor and the statistician responsible for the trial:  
a. 
Re-estimation of sample size using the observed rate of healing and dropout rate 
b. 
The difference in percentage of healed subjects  
c. 
The healing rate in Treatment arms 
d. 
The healing rate in the Control arm 
e. 
The power used in calculating the new sample size 
No other information will be shared with the sponsor or the statistician responsible for this 
trial. 
 

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10.5.2 Results of Interim Analysis 
 
The new sample size calculation is: 
Based on a pair-wise comparison of gekoTM 12h run-in vs treatment: 
From the interim data, there is a mean difference of 0.58 mm/week between run-in and treatment and 
a standard deviation of 0.97 mm/week.  
Assuming requirements of 80% power and p=0.05 (2-sided) 25 subjects would be needed in the 
gekoTM 12H group. (30) 
Little benefit is foreseen in continuing the gekoTM 6h group, as statistical significance is not 
expected at the projected number of subjects in this trial.  
From the results of the Interim Analysis the new Treatment Groups are: 
Group 
Description 
SC 
Standard care (multilayer, multicomponent compression intended for the 
treatment of VLU) 
geko 12h 
gekoTM version XW, W-3 or variant (12 h daily neuro-stimulation) and SC 
 
 
 
10.6 Treatment Groups 
The following treatment groups will be assessed: 
Group 
Description 
SC 
Standard care (multilayer, multicomponent compression intended for the 
treatment of VLU) 
geko 12h 
gekoTM version XW, W-3 or variant (12 h daily neuro-stimulation) and SC 
 
10.7 Description of Study Endpoints 
10.7.1 Primary Efficacy Endpoint 
The primary efficacy endpoint for the study is LHR from TV1 to EOT as compared with LHR 
from RV1 to TV1. LHRs will be measured by a blinded wound expert using digital images at 
RV1, TV1, EOT, and at HCV if scheduled. 

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Each participant will be used as his/her own control, i.e. a participant’s healing trajectory before 
commencement of treatment will be compared to his/her healing trajectory after introduction 
of treatment. 
Since significant non-homogeneity may be expected in VLU participants and their respective 
healing trajectories, a pre-treatment run-in phase will be used to allow each participant to be 
used as his/her own control, i.e. a participant’s healing trajectory before introduction of 
treatment will be compared to his/her healing trajectory after introduction of treatment. This 
allows an intra-group pair-wise comparison to evaluate the efficacy of each treatment regimen.  
Additionally, for each participant, it enables generation of a treatment healing rate normalised 
relative to an initial healing rate. Inter-group (albeit un-paired) comparisons based on this 
normalised value are likely to be more sensitive than comparison of raw healing rates.  
10.7.2 Secondary Efficacy Endpoints 
The secondary efficacy endpoints are:  
 Weekly LHR measured by an independent blinded wound expert using digital images taken 
at each weekly visit until EOT. 
 Wound healing status at baseline and EOT assessed by an independent blinded wound 
expert using PWAT to evaluate digital images taken at RV1, TV1, EOS, and at HCV, if 
scheduled. 
 Incidence of healing at end of study, as determined by the Investigator  
“Healing” of the study ulcer is determined by the PI or designee. “Healing” is defined as 100% 
re-epithelialised without drainage as confirmed at the Healing Confirmation visit (HCV).  
10.7.3 Participant reported secondary efficacy endpoints 
Participant reported secondary efficacy endpoints are: 
 Time from TV1 to clinically significant pain reduction measured using a Visual Analogue 
Scale (VAS) instrument. For the purpose of this protocol a clinically significant reduction 
of pain is a mean reduction of ≥ 20.65 mm or a mean decrease of ≥ 10-20% in pain as 
measured on a 0-100 mm VAS (23; 24). 
 Time from TV1 to first instance of no study ulcer pain measured using VAS. 
(No pain = < 5mm on VAS when VAS scores: 0-4 mm = no pain; 5-44 mm = mild pain; 
45-74 mm = moderate pain; and 75-100 mm = severe pain) (1). 
 Pain score at EOT measured using VAS.  
 Change from TV1 in QoL at EOT assessed using the CWIS.  
 Change from TV1 in QoL at EOT assessed using EQ-5D-5L.  
 
10.7.4 Safety Assessments 
Safety will be assessed using the following parameters:  
 Incidence of AEs  

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 Incidence of SAEs 
 Incidence of study ulcer infection 
 Incidence of study treatment related AEs (including gekoTM, compression bandaging and 
any dressings used to treat the study wound) 
 Incidence of investigational device (gekoTM) related AEs 
 
Pain in the ulcer site (sudden onset of pain or increase in pain during the study Treatment 
Phase)  
 10.8 Participant Disposition 
The disposition of all patients who sign an informed consent form (ICF) will be provided. The 
numbers of patients screened, randomised, completed, and discontinued during the study, as 
well as the reasons for all post-randomisation discontinuations will be summarised by treatment 
group, for all centres combined and each centre separately. Disposition and reason for study 
discontinuation will also be provided as a by-participant listing. 
10.9 Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarised by treatment group using 
appropriate descriptive statistics. 
10.10 Analysis Populations 
10.10.1 Intent to Treat Population 
The Intent-to-Treat (ITT) population is defined as the set of randomised participants who have 
at least one post-randomisation efficacy assessment for wound healing.  The ITT population 
will be the primary population for the analysis of primary and secondary endpoints. 
10.10.2Per Protocol Population 
The Per Protocol (PP) population is defined as the set of participants who meet the ITT 
population requirements, defined above, and who were not associated with a major protocol 
violation/deviation.  This population will be identified before the database lock. 
10.10.3 Safety population 
The Safety population is defined as any participant receiving treatment after randomisation. 
This population will be used for the analysis of safety parameters. 
 
10.11 Treatment Failures 
Participants who are withdrawn or discontinue during the Treatment Phase and/or who do not 
achieve healing during the Treatment Phase will not be replaced and will be considered 
treatment failures. 
 

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10.12 Analysis Methods  
A SAP will be developed and approved before the database is locked. The SAP will present the 
detailed statistical methodology to be used in analysing the efficacy and safety data from this 
study. 
All statistical tests will be two-sided and a 0.05% significance level maintained throughout the 
analyses.  
10.12.1 Efficacy Analyses 
Primary Endpoint: The primary efficacy endpoint is linear healing rate (LHR) from TV1 to 
EOT as compared with LHR from RV1 to TV1. LHRs will be measured by a blinded wound 
expert using digital images at RV1, TV1, and EOT.  
Within treatment groups, treatment phase will be compared to run-in phase by paired non-
parametric test (Wilcoxon signed rank). Effects will be compared between groups using non-
paired non-parametric tests (Mann-Whitney). 
Secondary Endpoints: 
Weekly LHR shall be compared as above. 
EOT healing status between groups shall be compared by Mann-Whitney U test on the PWAT 
scores.  Weekly LHR can be tested using the same method (and same wording) as final LHR. 
Incidence of healing shall be compared between groups using Fisher's exact test. 
Intra-group pain reduction measured on a visual analogue scale (VAS) will be analysed using 
paired t-test. 
Inter group differences in time to clinically significant reduction in VAS shall be tested using 
Mann-Whitney u-test. 
Intra-group changes to both Quality of Life (QoL) instruments in the study (CWIS and EQ-5D-
5L) shall be tested using Wilcoxon signed rank test. 
10.12.2 Safety Analyses 
The Safety population will be used for the analysis of safety assessments.   
For continuous variables data will be summarised by treatment using n, mean, SD, minimum 
and maximum values. For categorical variables data will be summarised by treatment using 
frequency and percentage.  
10.12.2.1 Adverse Events  
Adverse events will be coded using the latest version of MedDRA.  
Separate summaries of serious adverse events, and adverse events resulting in discontinuation 
of study treatment will be presented. 
 

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11 Adverse Events (Definitions and Reporting) 
The Investigator or duly trained designee(s) will be responsible for detecting, documenting and 
reporting AEs and SAEs during this study as detailed in this section of the protocol.  
11.1 Adverse Events 
An adverse event (AE) is defined as any unfavourable or unintended sign, symptom, or disease 
that occurs or is reported by the participant to have occurred, or a worsening of a pre-existing 
condition.  An AE may or may not be related to the study treatment.  
AEs will be elicited through direct questioning and participant reports. Any abnormality in 
physical examination findings or laboratory results that the Investigator believes is clinically 
significant to the research participant will be reported as an AE. Abnormal findings that are 
NOT clinically significant should not be recorded as an AE. 
11.2 Reporting and Follow-up of Adverse Events 
Report initiation for all AEs and serious adverse events (SAEs), (see Section 11.4) will begin 
at the time of the first run in phase visit  and will be reported up until the final study visit.  All 
events will be followed to resolution or until 30 days after the participant completes the study, 
whichever comes first.  A final assessment of outcome will be made at that time. 
AEs that emerge prior to the randomisation visit (TV1), will be recorded on an AE form.  Aside 
from being used to determine participant eligibility, this information will permit the 
Investigator to record the nature, duration and severity of any ongoing baseline medical 
conditions prior to the patient receiving study treatment. 
All AEs must be recorded in the participant’s medical records and on the CRF. AEs will be 
reported using customary medical terminology along with the following information:  the onset 
and end dates, whether the event is at the site of the study ulcer or at the site of the 
investigational device, whether the event is related to the study treatment, whether the event is 
related to the study ulcer, whether the event is considered to be an SAE (see Section 11.3), the 
impact the event had on study treatment (see Section 11.2.1), the Common Terminology 
Criteria for AEs (CTCAE) grade (intensity) of the event (see Section 11.2.2), the relatedness 
of the event (see Section 11.2.3), whether treatment was given as a result of the event (see 
Section 11.2.4), and the outcome of the event (see Section 11.2.5). 
11.2.1 Impact on Study Treatment 
The impact the event had on the study treatment will be assessed as either: none, study treatment 
interrupted, study treatment discontinued, or not applicable.  The “not applicable” assessment 
will be used only when the participant is no longer in the treatment phase of the protocol. 

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11.2.2 Intensity Assessment 
The guidelines outlined in CTCAE v4.03 will be used for assessing the intensity of the event. 
The general guidelines for assessing the AE grade appear below.  Full guidelines may be 
obtained at http://evs.nci.nih.gov/ftp1/CTCAE. 
Table 3: Common Terminology Criteria for AEs v4.03 General Guidelines 
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self 
care ADL†. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE.‡ 
* Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using telephone managing money etc 
† Self care ADL refer to bathing, dressing and undressing, feeding self, using toilet, taking medications, and not bed 
ridden. 
‡ Unlike the AE outcome assessment, a participant may have more than one Grade 5 event 
 
11.2.3 Relatedness Assessment 
Adverse events will be assigned a relationship (relatedness) to the study treatment.  The 
Investigator will be responsible for determining the relationship between an AE and the study 
treatment.  The type of event, organ system affected, and timing of onset of the event will be 
factors in assessing the likelihood that an AE is related to the study treatment.  Relatedness of 
AEs to study treatment will be classified as follows: 
 Not Related: No relationship exists between the AE and the treatment.  The event is 
attributed to a pre-existing medical condition or an intercurrent event unrelated to the study 
product. 
 Possibly Related:  Follows the treatment, but may have developed as a result of an 
underlying clinical condition or treatments/interventions unrelated to the study product. 
 Probably Related:  Follows the treatment, but is unlikely to have developed as a result of 
the participant’s underlying clinical condition or other treatment or other interventions. 
 Definitely Related:  Follows the treatment and physical evidence shows a convincing 
relationship to the treatment. 
 

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11.2.4 Treatment Given as a Result of the Event 
The event impact in terms of treatment provided will be as either: none, medication 
administered, therapy administered, surgery, or other (with a specification). 
 
11.2.5 Outcome Assessment 
The outcome of the event will be assessed as either: resolved, resolved with sequelae, ongoing, 
or death.  Only one AE per participant is allowed to have an outcome assessment as “death.”  
If there are multiple causes of death for a given participant, only the primary cause of death 
will have an outcome of death.   
11.3 Serious Adverse Events 
A SAE is defined as any AE that: 
 Results in death 
 Is life threatening (the participant is at immediate risk of dying from the adverse experience) 
 Requires participant hospitalisation or prolongs existing hospitalisation 
 Results in persistent or significant disability/incapacity  
 Is a congenital anomaly/birth defect 
 
11.4 Reporting of Serious Adverse Events 
Once the Investigator becomes aware of an SAE, he/she must report the SAE to Sponsor 
within 24 hours. 
Sponsor’s SAE Contact: 
Dr Kieron Day , PhD 
Tel: +44 (0)  7921 106253 
e-mail safety@firstkindmedical.com 
A written SAE report must include a full description of the event.  Additional supporting 
documentation may be requested and should be provided to Sponsor as and when it becomes 
available. Such documentation includes but is not limited to lab reports, electrocardiogram 
[ECG] reports, discharge summary, hospital notes, etc.   
The Investigator is also responsible for reporting all SAEs to the appropriate Institutional 
Review Board (IRB) or in accordance with local laws and regulations.  The Investigator is 
responsible for maintaining documentation in the study file that indicates the IRB has been 
properly notified.  

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11.5 SAE Follow-up 
All events will be followed to resolution or until 30 days after the participant completes the 
study.  A final assessment of outcome will be made at that time. 

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12 Direct Access to Source Data/Documentation 
Participants will be identified on CRFs by a unique participant identification number and on 
source documents by name and date of birth. No personal identifier will be used in any 
publication or communication used to support this research study. The participant identification 
number will be used if it becomes necessary to identify data specific to a single participant.  
The monitors, auditors, personnel authorised by the Sponsor, the local IRB, and regulatory 
agencies are eligible to review medical and research records related to this study as a part of 
their responsibility to protect human participants in clinical research and will be given direct 
access to source data and documentation (e.g., medical charts/records, printouts etc.) for source 
data verification, provided that participant confidentiality is maintained in accordance with 
local requirements. Access to electronic medical records may be governed by institution policy 
and each site will be required to ensure access while remaining compliant with institutional 
requirements. 
 
 
 

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13 Quality Control and Quality Assurance 
13.1 Monitoring Requirements 
In order to maintain knowledge of the progress of a study, the Sponsor's designated Clinical 
Research Associate (CRA)/monitor will visit the centres during the study as well as maintain 
frequent telephone and written communication. The Investigator will permit the Sponsor to 
monitor the study as frequently as is deemed necessary and provide access to medical records 
to ensure that data are being recorded adequately, that data are verifiable and that protocol 
adherence is satisfactory.  
The Investigator will permit representatives of the Sponsor and/or designated CRO to inspect 
all CRFs and corresponding study participant original medical records (source documents) at 
regular intervals throughout the study. Participant original medical records and other relevant 
data must be available to support all data recorded in the CRF. In addition to the original 
medical records, these data may include but is not limited to, study, laboratory and diagnostic 
reports, wound images and tracings, quality of life questionnaire, etc.  
Site inspections serve to verify strict adherence to the protocol and the accuracy of the data 
being entered on the CRFs, in accordance with applicable regulations. A Monitoring Log will 
be maintained at each study site which the monitor will sign, date and state the type of visit.  
The Investigator should be aware that the study site and participant records might be inspected 
and audited by the Sponsor or representatives of Sponsor or relevant regulatory authorities. 
13.2 Acceptability of Case Report Forms  
A CRF must be completed for each participant who has signed an informed consent form. For 
patients who are screen failures, this would be limited to the screen failure CRF page. All source 
documents and CRFs will be completed during or as soon as possible after the participant's 
visit. The Investigator will review CRFs to indicate that, to his/her knowledge, they are 
complete and accurate.  CRFs will be reviewed by the Sponsor’s CRA/ monitor, who will make 
a decision as to their acceptability.   
13.3 Modification of Protocol 
A modification or alteration to this protocol may not be undertaken without first obtaining the 
concurrence of Sponsor. Both the Lead Investigator and the Sponsor representative must sign 
and date the amendment prior to implementation.  In addition, the Lead Investigator must report 
all protocol amendments to, and receive all required approvals from, the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) PRIOR to implementation of any protocol 
amendment at the study centre, with two exceptions: 
1. 
When necessary to eliminate apparent immediate hazard to the participant; or 
2. 
When the modification involves only logistics or administration. 
In the event that a protocol change is proposed for all participants, the following procedure for 
a protocol amendment will be followed. An amendment must be in writing and it must be dated 

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by both the Sponsor and the Investigator. If necessary, the Sponsor will submit protocol 
amendments to the appropriate regulatory authorities and notify other Investigators using this 
protocol.  
An amendment may also require modification of the informed consent form. The Investigator 
will provide an approval letter for the amendment and revised informed consent form, if 
applicable, to the Sponsor. 
Any protocol amendments will be listed in the "Appendices" portion of the Table of Contents. 
13.4 Reporting Protocol Deviations 
The Investigator is obligated to follow the protocol without departure from the requirements 
written in the protocol. If the Investigator deviates from the protocol requirements, the Sponsor 
will make the determination as to whether the participant will continue in the study. The 
Sponsor also has the right to discontinue the participant for protocol deviations/violations. 
All protocol deviations must be documented in the CRFs. 

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14 Ethics and Regulatory Requirements 
This study is to be conducted in accordance with the specifications of this protocol and in 
accordance with principles consistent with Declaration of Helsinki, Good Clinical Practice 
(GCP) and currently applicable regulations.  
No protocol changes will be implemented without the prior review and approval of the relevant 
IRB/IEC s, except where it may be necessary to eliminate an immediate hazard to a research 
participant (See Section 14.1).  
Additionally, all study products used in this study are manufactured, handled and stored in 
accordance with applicable Good Manufacturing Practices (GMP) and the products provided 
for this study will be used only in accordance with this protocol. 
14.1 Institutional Review Board/Independent Ethics Committee 
The Principal Investigator will provide the IRB/IEC with all appropriate materials as required 
by their IRB/IEC, including but not limited to the clinical study protocol, informed consent 
form, and any advertising materials. The study will not be initiated until the IRB/IEC provides 
written approval of the aforementioned documents and until approval documents have been 
obtained by the Principal Investigator and Sponsor or Sponsor designee. The Investigator will 
not participate in the decision. If the Investigator is an IRB or IEC member, documentation 
must be provided indicating recusal from the approval process. Appropriate reports on the 
progress of this study by the Principal Investigator will be made to the IRB/IEC as required by 
local and applicable government regulations and in agreement with policy established by the 
Sponsor. The Investigator is required to maintain an accurate and complete record of all written 
correspondence to and received from the IRB/IEC, and must agree to share all such documents 
and reports with the Sponsor. 
No changes from the final approved protocol will be initiated without the IRB/IEC’s prior 
written approval or favourable opinion of a written amendment, except when necessary to 
eliminate immediate hazards to the participants or when the change involves only logistics or 
administration.   
14.2 Investigator’s Responsibilities 
The Investigators are responsible for performing the study in full accordance with the 
specifications of this protocol and in accordance with principles consistent with Declaration of 
Helsinki, Good Clinical Practice (GCP) and currently applicable regulations. Information 
regarding any study centres participating in this study that cannot comply with these standards 
will be documented. 
14.3 Participant Informed Consent Requirements 
Written and oral information about the study in a language understandable by the patient will 
be given to all patients by the Investigator and/or designee. Written informed consent will be 
obtained from each patient before any procedures or assessments that would not otherwise be 
required for the care of the patient are done and after the aims, methods, anticipated benefits, 
potential hazards, and insurance arrangements in force are explained and the patient has been 

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given sufficient time to ask questions and consider participation in the study. It will also be 
explained to the patients that they are free to refuse entry into the study and free to withdraw 
from the study at any time without prejudice to future treatment. It is permissible for a third 
person (e.g., a family member) to be present during the explanation of the study. 
The written Informed Consent Form (ICF) is to be in compliance with Good Clinical Practice 
(GCP) guidelines. The Sponsor and/or designated Contract Research Organisation (CRO) will 
approve the ICF and all amendments to the ICF prior to submission to the IRB/IEC. A copy of 
the ICF to be used will be submitted by the Investigator to the IRB/IEC for review and approval 
prior to the start of the study. Each study site must provide the Sponsor with an unsigned copy 
of IRB/IEC-approved ICF along with applicable documentation to support this approval. The 
original signed ICF is retained in the participant's study records, and a copy is provided to the 
participant. A second copy may be filed in the participant’s medical record, if allowed by 
institutional policy.  
 

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15 Data Handling and Record Keeping 
15.1 Recording and Collection of Data 
The primary source document for this study will be the participant's medical record. If separate 
research records are maintained by the Investigator(s), the medical record and the research 
records will be considered the source documents for the purposes of auditing the study.  
Applicable source data will be manually transcribed to approved CRFs. The Investigator is 
ultimately responsible for the accuracy of the data transcribed on the forms. All source 
documents and CRFs will be completed as soon as possible after the participant's visit. 
The Principal Investigator (PI) will review CRFs to indicate that, to his/her knowledge, they 
are complete and accurate. If further changes are made after this, the PI will need to again sign 
the Investigator signature page. Designated source documents will be signed and dated by the 
appropriate study personnel. Investigators must agree to complete and maintain source 
documents and CRFs for each participant in the study. 
All research data will be entered, either electronically or manually, into a computerised 
database.  
The PI will maintain a confidential list of study participants which will include each 
participant’s study number, name, date of birth and unique hospital identification number if 
applicable. This list will be kept by the PI and will not be collected by Sponsor. A notation will 
be made in the participant’s case history/medical chart that he/she is participating in a clinical 
study and has provided a signed and dated ICF. The PI must also maintain a separate screening 
log of all the patients screened for participation in the study; it should include gender; age; 
eligibility status; reason for ineligibility, if applicable; and study allocated participant number, 
if applicable.   
15.2 Clinical Data Management 
The Sponsor and/or designated CRO will be responsible for the processing and quality control 
of the data. Data management will be carried out as described in the Sponsor’s or CRO’s 
standard operating procedures (SOPs) for clinical studies. 
The handling of data, including data quality control, will comply with applicable regulatory 
guidelines and the Sponsor’s SOPs as well as provisions of a study-specific Data Management 
Plan. 
15.3 Archiving 
All study documentation at the Study site and Sponsor site will be archived in accordance with 
Sponsor’s quality standards and SOPs. 
The Study site will maintain all research records, reports, and case history reports for a period 
of 15 years after study closure.  
At the completion of the study, details of the archival process must be provided to the Sponsor. 
Study records are subject to inspection by applicable health and regulatory agencies at any time.   

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Records to be retained at the Study site include, but are not restricted to: 
 Source data and the primary records upon which they are based (e.g., participant’s progress 
notes, adverse event data, test results, and any other diagnostic procedures required to 
evaluate the progress of the study). 
 Signed protocols and protocol amendments 
 Product accountability records 
 Study personnel signature log 
 Monitoring logs 
 Correspondence to and from the Sponsor, designee and IRB/IEC 
 Principal Investigator and co-Investigator(s) Curriculum Vitaes (CVs) 
 Signed ICFs 
 Patient screening and randomisation log 
 SAE reports 
 IRB/ICE approval letters and correspondence if applicable 
 Completed QoL questionnaires 
 Other documents pertaining to the conduct of the study 
These documents must be maintained and kept on file by the Study site so that the conduct of 
the study can be fully documented and monitored. 

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16 Publication Plan 
Manuscripts and abstracts will be prepared by both the Investigator(s) and the Sponsor. The 
results of the study may be published in scientific literature and may also be used in submissions 
to regulatory authorities. It is the intent of the Sponsor, and the Lead Investigator to publish or 
present the study results together with the other Investigators, unless specific permission is 
obtained in advance from the Sponsor to publish separate results. Co-authorship with any of 
the Sponsor’s personnel will be discussed and mutually accepted upon submission of a 
manuscript or publication. Authorship will be decided upon in accordance with the ICMJE 
(International Committee of Medical Journal Editors) guidelines. 
The publication process commences with Sponsor forming a Publication Committee. The 
Publication Committee will publish first. The Investigators can proceed with publication after 
publication by the Publication Committee.  
All information concerning the Sponsor’s operations (such as patent applications, formulae, 
manufacturing processes, basic scientific data, or formulation information supplied to the 
Investigator and not previously published) is considered confidential by the Sponsor and shall 
remain the sole property of the Sponsor. Investigators agree not to use it for other purposes 
without the Sponsor’s prior written consent. 
It is understood by the Investigators that the Sponsor will use the information developed in this 
clinical study in connection with the development of the gekoTM. Therefore, this information 
may be disclosed as required to other Investigators or appropriate regulatory authorities. By 
agreeing to participate in this clinical study, the Investigator understands that he/she has an 
obligation to provide the Sponsor with complete test results and all data developed during this 
study. 
Publication and Disclosure: Because this is a multi-centre study, site and Investigator 
shall not independently publish, publicly disclose, present or discuss any results of or 
information pertaining to site’s and Investigator’s activities conducted under this 
agreement until such a multi-centre publication is released under Sponsor’s direction; 
provided, however, that if a publication is not released within eighteen (18) months after 
completion of analysis of all study data from all studies conducted within the multi-
centre study, site and Investigator shall have the right to publish the results of and 
information pertaining to site’s and Investigator’s activities conducted under this 
protocol and the clinical study agreement. Site and Investigator agree to submit any 
proposed manuscript, presentation or other public disclosure regarding the study to 
Sponsor for review at least sixty (60) days prior to submitting such proposed manuscript 
to a publisher or delivering or making such presentation or other public disclosure to 
any third party. Within sixty (60) days of its receipt, Sponsor shall advise site and/or 
Investigator, as the case may be, in writing of any information contained therein that is 
confidential information (other than research results included in a proposed 
manuscript) or that may impair sponsor’s ability to obtain patent protection. Sponsor 
shall have the right to require site and/or Investigator, as applicable, to remove 
specifically identified confidential information (but may not require removal of research 
results from a proposed manuscript) and/or to delay the proposed submission or 

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delivery of the proposed manuscript or presentation, or other public disclosure, for an 
additional sixty (60) days to enable Sponsor to seek patent protection. Site and 
Investigator shall not publish, publicly disclose, present or discuss any results of or 
information: (a) pertaining to site’s and Investigator’s activities prior to completion of 
the study, even if the multi-centre study or the study is terminated before its completion 
and the final clinical study report is signed off, or (b) with respect to any endpoints or 
analyses other than those specified in this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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17. References 
1. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of 
postoperative pain. Jensen, M P, Chen, C and Brugger, A M. 4, 2003, Journal of Pain, pp. 407-414. 
2. Antibiotics and antiseptics for venous leg ulcers. O'Meara, S, Al-Kurdi, D and Ovington, L G. 23 Jan 2008, 
Cochrane Database of Systematic Review, Vol. 1, p. CD003557. 
3. Healing times and the need for hospitalization for leg ulcers of different etiologies. Läuchli, S, et al. 12, Dec 
2013, Hautarzt, Vol. 64, pp. 917-22. 
4. Martorell hypertensive ischemic leg ulcer: a model of ischemic subcutaneous arteriolosclerosis. Hafner, J, et 
al. 9, September 2010, Archives of Dermatology, Vol. 146, pp. 961-8. 
5. Compression for preventing recurrence of venous ulcers. Nelson, E A and Bell-Syer, S E. 9 Sept 2014, 
Cochrane Database of Systematic Reviews, Vol. 9, p. CD002303. 
6. Long-term prognosis for patients with chronic leg ulcers: a prospective cohort study. Nelzén, O, Bergqvist, D 
and Lindhagen, A. 5, May 1997, European Journal of Vascular and Endovascular Surgery, Vol. 13, pp. 500-
8. 
7. Stockings and the prevention of recurrent venous ulcers. Samson, R H and Showalter, D P. 4, Apr 1996, 
Dermatologic Surgery, Vol. 22, pp. 373-6. 
8. A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. Phillips, 
T, et al. 1, Jul 1994, Journal of the American Academy of Dermatology, Vol. 31, pp. 49-53. 
9. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Jünger, M, et al. 6 Pt 2, 2000, 
Microcirculation, Vol. 7, pp. S3-12. 
10. Venous ulcers. Etufugh, C N and Phillips, T J. 1, Feb 2007, Clinics in Dermatology, Vol. 25, pp. 121-30. 
11. Managing the patient with venous ulcers. de Araujo, T, et al. 4, 18 Feb 2003, Annals of Internal Medicine, 
Vol. 138, pp. 326-34. 
12. Compression bandages and stockings for venous leg ulcers. Cullum, N, et al. 2000, Cochrane Database of 
Systematic Review, Vol. 2, p. CD000265. 
13. Chronic ulceration of the leg: extent of the problem and provision of care. Callam, M J, et al. 6485, 22 Jun 
1985, British Medical Journal, Vol. 290, pp. 1855-6. 
14. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin 
equivalent. Human Skin Equivalent Investigators Group. Falanga, V, et al. 3, mAR 1998, aRCHIVES OF 
dERMATOLOGY, Vol. 134, pp. 293-300. 
15. Revisiting the essential role of oxygen in wound healing. Gordillo, G M and Sen, C K. 3, Sept 2003, American 
Journal of Surgery, Vol. 186, pp. 259-63. 
16. Bhattacharya, V and Stansby, G. Postgraduate Vascular surgery - A candidates guide to the FRCS. s.l. : 
Cambridge University Press, 2010. 
17. Augmentation of venous, arterial and microvascular blood supply in the leg by isometric neuromuscular 
stimulation via the peroneal nerve. Tucker, A, et al. 1, Spring 2010, The International Journal of Angiology, 
Vol. 19, pp. e31-7. 

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18. The effectiveness of a novel neuromuscular electrostimulation method versus intermittent pneumatic 
compression in enhancing lower limb blood flow. Jawad, H, et al. 2, Apr 2014, Journal of Vascular Surgery: 
Venous and Lymphatic Disorders, Vol. 2, pp. 160-5. 
19. Haemodynamic changes with the use of neuromuscular electrical stimulation compared to intermittent 
pneumatic compression. Williams, K J, Moore, H M and Davies, A H. 5, Jun 2015, Phlebology, Vol. 30, pp. 
365-72. 
20. Evaluation of a muscle pump-activating device for non-healing venous leg ulcers. Harris, C, et al. 6, Dec 
2017, International Wound Journal, Vol. 14, pp. 1189-1198. 
21. Jones, N J, et al. A case series evaluating the gekoTM neuromuscular electrostimulation device on lower limb 
wounds of differing aetiology.  
22. A simple mathematial Model for Wound Closure Evaluation. Vidal A, Medieta Zeron H, Giacaman I et al. 
1-3, s.l. : J Am Coll Clinical Wound Spec., Vol. 29;7. 
23. Topical agents or dressings for pain in venous leg ulcers. Briggs, M, Nelson, E A and Martyn-St James, M. 
4, 14 Apr 2010, Cochrane Database of systemic reviews, p. CD001177. 
24. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT 
recommendations. Dworkin, R H, et al. 2, Feb 2008, Journal of Pain, Vol. 9, pp. 105-21. 
25. Validation of Venous Clinical Severity Score (VCSS) with other venous severity assessment tools from the 
American Venous Forum, National Venous Screening Program. Passman, M A, et al. Dec 2011, Journal of 
Vascular Surgery, pp. 2S-9S. 
26. Grey-Bruce Health Network. Evifence-Based Care Program. [Online] [Cited: 04 01 2018.] 
http://www.gbhn.ca/ebc/documents/ASSESSMENTOFPITTINGEDEMA.pdf. 
27. Wound assessment. Grey, J E, Enoch, S and Harding, K G. 7536, 4 Feb 2006, British Medical Journal, Vol. 
332, pp. 285-8. 
28. The Canadian Bandaging Trial: Evidence-informed leg ulcer care and the effectiveness of two compression 
technologies. Harrison, M B, et al. 13 Oct 2011, BMC Nursing, Vol. 20, pp. 1-12. 
29. An overview of randomization techniques: An unbiased assessment of outcome in clinical research. Suresh, 
K P. 1, 2011, Journal of Human Reproductive Sciences , Vol. 4, pp. 8-11. 
30. Dhand, N. K., & Khatkar, M. S. Statulator: An online statistical calculator. SamplSize Calculator for 
Comparing 
Two 
Paired 
Means. 
[Online] 
[Cited: 
19 
March 
2020.] 
http://statulator.com/SampleSize/ss2PM/html. 
 
 
 
 

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18 APPENDICES 
Appendix 1: Instructions for Use and Fitting Instructions geko™ Devices 
 
Sent under separate cover. 
 
 
 
 
 
 
 
 
 

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Appendix 2: Photographic Wound Assessment Tool (PWAT) 
 
 
 
 

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Appendix 3: Venous Ulcer Clinical Severity Score 
Pain 
None 
Occasional, not restricting activity or requiring analgesia 
Daily, moderate activity limitation, occasional analgesia 
Daily, severe limiting activities or requiring regular use of analgesia 
Varicose veins 
None 
Few, scattered, branch varicose veins  
Multiple: greater saphenous varicose veins confined to calf or thigh 
Extensive: thigh and calf or greater saphenous and lesser saphenous 
distribution 
Venous Edema 
None 
Evening ankle edema only (edema must be a daily occurrence) 
Afternoon edema, above ankle (edema must be a daily occurrence) 
Morning edema above ankle and requiring activity change, elevation 
(edema must be daily occurrence) 
Skin pigmentation 
None or focal low intensity (tan) (focal pigmentation over varicose 
veins does not apply) 
Diffuse, but limited in area and old (brown) 
Diffuse over most of gaiter distribution (lower 1/3) or recent 
pigmentation (purple) 
Wider distribution (above 1/3) and recent pigmentation 
Inflammation 
None 
Mild inflammation, limited to marginal area around ulcer 
Moderate inflammation, involves most of the gaiter area (lower 1/3) 
Severe inflammation (lower 1/3 and above) or significant venous 
eczema 
Induration 
None, 
Focal, circum-malleolar (<5cm) 

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Medial or lateral (< lower 1/3), 
Entire lower 1/3 or leg or more 
Number of active ulcers 
0,  
1,  
2,  
>2 
Active ulceration, 
duration 
None, 
< 3 months, 
3 – 12 months, 
> 12 months 
Active ulcer, size (largest 
ulcer dimensions) 
None, 
< 2cm diameter  
2 – 6 diameter,  
> 6 diameter 
Compression therapy 
Not used or not compliant, 
Intermittent use of bandages 
Wears bandages most of the time, 
Full compliance 

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Appendix 4:  EQ-5D-5L Questionnaire 
 
 

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Appendix 5: Cardiff Wound Impact Schedule (CWIS) 
 
 
 
 
 

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Appendix 6: Participant Diary 
 
Dear Participant, 
Please use this sheet to keep a record of your gekoTM use over the course of the study. If you 
are unable to use the gekoTM device for any reason, please contact your doctor or research 
nurse as soon as possible.   Please use the gekoTM device daily as instructed. If you forget to 
use completely, record on this sheet that the gekoTM device was not used. Do not try to 
squeeze in extra doses by using the gekoTM device for longer periods the next day. 
 
Participant ID - xxxxx 
 
TVx - TVx 
Date 
dd/mm/yyyy
Time you 
switched on the 
gekoTM device 
(use 24hour 
format or 
include am/pm) 
Time you 
switched off the 
gekoTM device 
(use 24hour 
format or 
include am/pm) 
Device 
setting 
(Please 
circle the 
setting 
used) 
Label 
Any 
comments 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
Please insert the 
label on gekoTM 
device pouch 
here
 

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5    6    7  
8 
9    10 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
 
 
 
Device turned 
off by itself  
1    2    3  
4 
5    6    7  
8 
9    10 
Please insert the 
label on gekoTM 
device pouch 
here 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
To be completed by the investigator
 
Date collected the completed diary –  
 
Initials of the person collected – 
 
Signature of the person collected –  

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Appendix 7: Protocol Amendments 
Details of any protocol amendments following Ethics Committee approval to be recorded here 
 
Change 
Updated Protocol Version 
Number and Date
Details of Change 
1  
10.5 16/04/2018 
Updates to inclusion/exclusion 
criteria, minor corrections 
2 
10.6 15/10/2018 
Updates to inclusion exclusion 
criteria & adding Follow-up 
phase
3 
10.7 14/01/2019 
Removal of the words ‘high 
level’ from ‘multilayer, 
multicomponent high 
level compression 
therapy’ 
 

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5 
10.8 16/08/2019 
Minor spelling corrections and the 
following amendments: 
1. Addition of details for Clinical 
Affairs Manager to page 2 
2. Addition of Firstkind Ltd Head 
of Clinical Affairs to Protocol 
Approval Page 
3. Addition of wording ‘or within 
8 weeks of study entry (i.e. 
RV1)’ to  inclusion criterion 
7, section 4.1 Run-in Phase, 
Schedule of Events and 
section 9.2 ABPI 
4. Removal of wording from 
section 4.1 Run-in Phase 
‘Any AEs during run in 
phase are to be recorded in 
the participant’s medical 
history’ 
5. Removal of the wording ‘and 
that occurred after initiation 
of the Treatment Phase of the 
study’ from section 11.1 
6. Addition of the wording ‘in the 
run in phase’ and ‘AEs will be 

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recorded on an AE form’ to 
section 11.2 
7. Sponsor SAE contact details 
updated on page 61 
6 
28/08/2019 
 
1. Addition of the wording ‘. At 
the randomisation visit, the 
study ulcer needs to be   ≥ 2 
cm2 and ≤ 30 cm2. If other 
ulcerations are present on the 
same leg, they need to be at 
least 2cm away from the study 
ulcer’ to section 4.2.2 
 
2. Inclusion Criterion 6 - 0.8-1.2 
replaced with 0.75-1.24  
 
7 
28/10/2019 
1. Addition of Appendix 8 
Sub-study 
2. Addition of geko™ W-2, 
XW-2 & T-3 IFU to 
Appendix 1 
8 
V11.0  
1. Change 
in 
Project 
Manager details 
2. Analysis 
change 
from 
PAR to LHR 
3. Interim Analysis changed 
from 60% randomized to 
60% enrolled. 
4. Addition 
of 
Vidal 
reference 
9 
V12.0 
1. Removal of 6h gekoTM 
2. Results 
of 
Interim 
Analysis 
3. Inc 
Criteria 
4: 
Two 
separate 
wounds 
not 
allowed 
 
 
 

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Appendix 8: Sub-study to the VLU efficacy study at selected clinical sites to determine 
whether oedema prevents neuromuscular stimulation by the geko™ device in a sub-set of 
VLU patients. 
Introduction 
The VLU Efficacy Study has shown an un-expected number of patients who do not respond to the W-
2 geko™ device. In the parent study, 24% of patients were found to be non-responders to stimulation 
by the device as evidenced by a lack of dorsiflexion, the involuntary movement of the lower leg / foot 
at the maximum tolerable device setting. This is in contrast to a study following orthopaedic patients 
after total knee replacement, where only 5% of patients were found not to respond to stimulation by 
the device (unpublished data). 
It is thought that excessive oedema in the area of the geko™ device application site may be preventing 
neuromuscular stimulation in VLU patients in the parent study. 
In this sub-study, the sub-set of non-responders from the parent study, instead of being excluded, may 
continue in the study and receive their standard care with the aim to reduce oedema during the Run-in 
Phase. Subjects will also be evaluated at the start of the Run-in Phase for their response to a higher 
out-put T-3 geko™ device and tested weekly 
through-out the Run-in Phase with both W-2 or variant and T-3 geko™ devices. At the end of the 
Run-in Phase and following re-evaluation of their response to the W-2 or variant geko™ device, 
responders to the W-2 or variant geko™ device will re-join the treatment phase of the main protocol. 
Non-responders will be excluded at this stage. 
It is hoped the results from this sub-study will show a positive correlation between treatment of 
excessive leg oedema and response to neuromuscular stimulation by the W-2 or variant geko™ device 
in VLU patients previously identified as non-responders in the VLU Efficacy Study. 
This may be of two fold benefit to these patients: 
1. Addressing oedema may  ameliorate complications associated with untreated and persistent 
oedema, which can impede wound healing by obstructing blood flow throughout the body and 
to the wound site resulting in hypoxia,  a key factor known to limit wound healing (15) 
2. Treatment of oedema may also facilitate neuromuscular stimulation by the 
W-2 or variant geko™ device thus increasing blood flow, circulation and delivery of oxygen 
to the wound site (17, 19, 20, 21) 
Study Objectives 
This sub-study seeks to determine whether oedema in the area of the W-2 geko™ or variant device 
application site prevents neuromuscular stimulation by the device.   
Subject Population 
Subjects will be a sub-set of subjects enrolled in the parent study at selected sites, following the same 
Inclusion / Exclusion criteria as per Section 3 of the main protocol, but who do not respond to the W-
2 or variant geko™ device i.e. subjects who do not have an involuntary movement (dorsiflexion) of 
the lower leg / foot at the maximum tolerable device setting without the compression bandaging in 
place. Subjects must also have evidence of oedema, as determined by the Venous Clinical Severity 
Score (see section 4.1 of main protocol and Castor EDC - step 13). 
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Obtaining a separate informed consent for participation in the sub-study is not required and a subject 
may withdraw their consent to participate in the sub-study at any time as per Section 5 of the main 
protocol. 
 
The investigator can withdraw a subject from the sub-study, if in his or her clinical judgment, it is in 
the best interest of the subject or if the subject cannot comply with elements of the sub-study protocol 
that are critical for safety or necessary for the scientific integrity of the study. If the investigator 
withdraws a subject from the study, the investigators will explain the reason for withdrawing the 
subject. 
 
Study Schedule 
All sub-study visits will be conducted according to the same time frame outlined in the Study 
Schedule (Section 4) of the existing main protocol. A schematic picture of the sub-study flow is 
provided in Figure1. 
Run-in Phase 
During the Run-in Phase, subjects will be evaluated on a weekly basis and study assessments 
performed as follows, see also Table 1.  
 
Remove compression bandaging 
 
Confirm subject does not respond to the W-2 or variant geko™ device by absence of 
dorsiflexion an  involuntary movement of muscles in the lower leg / foot at the maximum 
tolerable device setting If subject does not respond, test subject’s response to the higher out-
put T-3 device. Subject’s do not need to exhibit a positive response to the T-3 geko™ device 
to continue in the sub-study (RV1 only). Note: It is important that the device is applied to 
clean dry skin. Prior to application of the device, skin should be washed with mild soapy 
water, rinsed and dried thoroughly. Do NOT apply moisturiser at the device fitting site 
 
Measure ABPI if a valid ABPI reading has not been taken within 8 weeks of RV1 (RV1only) 
 
Confirm eligibility (RV1 only). If the patient is eligible, continue with the following 
procedures.  
Note: qualified subjects who do not wish to participate in the sub-study are not eligible to 
continue in the main study and an early termination eCRF should be completed in EDC. 
 Record medical history and study ulcer history (RV1 only). 
 Administer the CWIS and EQ-5D-5L questionnaires in the participant’s primary 
language (RV1 only). 
 Perform physical examination and assess Body Mass Index (RV1 only). 
 Assess concomitant medications (con-meds) and update con-med form in EDC as 
appropriate). 
 Assess compression bandaging (See Section 9.8). 
 
Figure 1. Sub-study flow chart 

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 Assess leg oedema using a tape measure to determine leg circumference at the level 
of the geko™ device application site. Using an indelible surgical pen, mark a 
reference point on the leg, to ensure weekly measurements are taken at the same place 
on the leg.  
 Record study ulcer location, history and duration (RV1 only). 
Note: ‘Study ulcer location’ is defined by the ulcer being on the left or right leg, by the 
location of the ulcer on the malleolus, low gaiter or high calf, and by the positioning of 
the ulcer as lateral, medial, anterior or posterior. 
 Administer the study ulcer pain VAS assessment.  
 Determine Venous Clinical Severity Score (RV1 only) Assess for AEs - Any AEs 
occurring during the Run-in Phase are to be recorded on an AE form in EDC. 
 Cleanse the study ulcer.  
Screening
Recruitment
RV1
Respond to W2 or 
variant geko™
Continue to Parent  
Study
RV1
Do not respondto 
W2 or variant geko™
Test with T3 geko™ 
and continue to
Sub Study
RV2
Respond to W2 or 
variant geko™
Return to Parent 
Study
RV2
Do not espond to 
W2 or variant geko™
Test with T3 geko™ 
and continue in
Sub Study
RV3
Respond to W2 or 
variant geko™
Return to Parent 
Study
RV3
Do not respond to
W2 or variant geko™ 
Test with T3 geko™ 
and continue in
Sub Study
RV4
Respond to W2 or 
variant geko™
Return to Parent 
Study
RV4
Do not respond to 
W2 or variant geko™
Test with T3 geko™ 
and continue in
Sub Study
RV5
Respond to W2 or 
variant geko™
Return to Parent 
Study
RV5
Do not respond to 
W2 or variant geko™
Test with T3 geko™ 
EXIT

Protocol Number FSK-VLU-004 
PRIVATE AND CONFIDENTIAL 
Version 12.2 
 
Date: 22May2020 
 
Page 92 of 93 
 
 
 Obtain a digital image of the study ulcer (if debridement is planned, this is the Pre-
debridement image). Note: all study ulcer measurements will be performed using the 
pre-debridement images.  
 At the discretion of the Investigator, perform debridement of the study ulcer to obtain 
a clean, granulating ulcer base with minimal adherent slough.  
 If applicable, obtain a post-debridement digital image of the study ulcer  
 Apply standard care.  A non-adherent (NA) wound contact dressing and/or an 
absorbent dressing may be used at Investigator’s discretion if required in addition to 
the compression system.  
 Record all dressing use 
 Assess for any AEs since signing ICF 
 Schedule next study visit in one week’s time 
  
The Run-in phase ends with RV5/TV1 which is also the first visit of the Treatment Phase.  
 
Treatment Phase 
At the first Treatment Phase (TV1), once compression bandaging has been removed, confirm subject’s 
response to the W-2 or variant geko™ device by presence of involuntary movement of muscles 
(dorsiflexion) in the lower leg / foot at the maximum tolerable device setting. If the subject does not 
respond to the W-2 or variant device the subject should be exited from the study and an early 
termination eCRF completed in EDC.  
Once a subject’s continued eligibility has been confirmed, randomisation and assignment to study 
treatment will take place and the subject will re-join the Treatment Phase of the main protocol and 
assessments completed as per the main protocol from section 4.2 onwards. Statistical analysis will be 
carried out using the Student’s t-test 
 
 
 

Protocol Number FSK-VLU-004 
PRIVATE AND CONFIDENTIAL 
Version 12.2 
 
Date: 22May2020 
 
Page 93 of 93 
 
 
Table 1.  Run-in Phase: Schedule of Sub-Study Assessments (assessments in bold are sub-study 
specific)  
Activity/Assessment 
RV1 
RV2 
RV3 
RV4 
RV5/TV1 
Informed consent 
√ 
 
 
 
 
Remove compression bandaging and assess 
response to 
W-2 or variant geko TM   
√∞ 
√∞ 
√∞ 
√∞ 
√∞ 
Asses response to 
T-3 geko TM    
√∞ 
√∞ 
√∞ 
√∞ 
√∞ 
Ankle-Brachial Index (ABPI) if a valid ABPI 
reading has not been taken within 8  weeks of 
RV1 
√ 
 
 
 
 
Confirmation of eligibility 
√ 
 
 
 
 
Assessment of leg oedema 
√¥ 
√¥ 
√¥ 
√¥ 
√¥ 
Medical history 
√ 
 
 
 
 
CWIS, EQ-5D-5L and assessments 
√ 
 
 
 
 
Physical examination and BMI 
√ 
 
 
 
 
Concomitant medications 
√ 
√ 
√ 
√ 
√ 
Assessment of compression bandaging 
√ 
√ 
√ 
√ 
√ 
Study ulcer history 
√ 
 
 
 
 
Study ulcer pain (VAS) assessment 
√ 
√ 
√ 
√ 
√ 
Venous Clinical Severity Score 
√ 
 
 
 
√ 
Assess for AEs 
 
√ 
√ 
√ 
√ 
Study ulcer cleaning 
√ 
√ 
√ 
√ 
√ 
Study ulcer surrounding skin assessment 
√ 
 
 
 
 
Study ulcer image(s) 
√⌘ 
√⌘ 
√⌘ 
√⌘ 
√⌘ 
Study ulcer debridement 
√§ 
√§ 
√§ 
√§ 
√§ 
Application of compression 
√¶ 
√¶ 
√¶ 
√¶ 
√¶ 
Assessment for AEs since signing ICF 
√ 
√ 
√ 
√ 
√ 
Scheduling of next visit 
√ 
√ 
√ 
√ 
√ 
∞ Presence of involuntary movement (dorsiflexion) of muscles in the lower leg and dorsiflexion of the foot at the maximum tolerable 
device setting W-2 or variant and T-3 before addition of compression bandaging 
 ¥   Assess leg oedema using a tape measure to determine leg circumference at the level of the geko™ device application site. .Using an 
indelible surgical pen, mark a reference point on the leg, to ensure weekly measurements are taken at the same place on the leg.  
§ Study ulcer debridement at Investigator’s discretion. N.B All study ulcer measurements will be performed using the pre-debridement 
images. 
⌘ If debridement is performed a pre-debridement and a post-debridement image is taken.  
¶ A non adherent (NA) wound contact dressing and/or an absorbent dressing may be used at Investigator’s discretion if required in addition 
to the compression system.