A Traditional Feasibility Study to Assess the Safety and Effectiveness of the Biodegradable Temporizing Matrix (BTM) in the Treatment of Deep Burn Skin Injuries.
Phase: NA
Conditions: Burns
Sponsor: PolyNovo Biomaterials Pty Ltd.

Cover Page for Protocol 
 
Sponsor name: 
PolyNovo Biomaterials Pty Ltd 
NCT number: 
NCT02905435 
Protocol: 
CP-002 
Study title: 
Assessment of Safety and Effectiveness of Biodegradable 
Temporizing Matrix in the Treatment of Deep Burn Skin Injuries 
Version: 
5.0 
Document date: 
19 December 2017 
 

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Title 
A Traditional Feasibility Study to Assess the Safety and Effectiveness of the 
Biodegradable Temporizing Matrix (BTM) in the Treatment of Deep Burn Skin Injuries. 
 
Protocol Number: 
CP-002 
 
Funding Mechanism: 
Biomedical Advanced Research and Development Authority (BARDA) 
Contract # HHO100201500021C. 
 
IDE Number: 
G160130 
 
Sponsor:  
PolyNovo Biomaterials Pty. Ltd.  
2/320, Lorimer Street 
Port Melbourne 3207, Victoria, AUSTRALIA 
 
Principal Investigator: 
Dr. Marcus JD Wagstaff BSc (Hons), MBBS, PhD, FRCS (Plast), FRACS 
Specialist Plastic and Burn Surgeon, Department of Plastic and Reconstructive 
 Surgery, 
Royal Adelaide Hospital, North Terrace, Adelaide 5000, South Australia, 
AUSTRALIA. 
Mobile: XXX XXX XXXXXX  
Email: XXXXXXXXXXXXXXXXX 
 
Medical Monitor: 
William Crafford 
PPD 
929 North Front Street  
Wilmington, NC 28401-3331  
United States  
Phone: XXXXXXXXXXXX 
Email: XXXXXXXXXXXXXXXXX 
 
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STATEMENT OF COMPLIANCE 
The clinical investigation shall be conducted in accordance with the ethical principles that 
have their origin in the Declaration of Helsinki, in compliance with International 
Conference on Harmonization Good Clinical Practices (ICH-GCP), the International 
Organization for Standardization (ISO) 14155 International Standard and any regional or 
national regulations, as appropriate. 
All additional requirements imposed by the Institutional Review Boards (IRBs) or US Food 
and Drug Administration (FDA) will be followed. Any subsequent instruction from either 
authority will be followed. PolyNovo has indemnity insurance to cover the trial. 
The responsibilities of the Clinical Investigator are set forth in the Declaration of Helsinki, 
ISO 14155-1 and ISO 14155-2, and 21 Code of Federal Regulations (CFR), Part 812, 
dealing with the investigational device exemptions. The Investigator must also comply 
with the requirements dealing with informed consent and protection of human subjects 
including those set out in 32 CFR 219, 10 U.S.C. 980, and, as applicable, 21 CFR Parts 
11, 50, 54, 56, 312, 45 CFR Part 46 (Federalwide Welfare Assurance). For trial extensions 
involving United States Territories, the ICH [E6; 62 Federal Register 25691 (1997)] as 
well as other applicable federal and state regulations will also apply.  
 

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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
 
Site Investigator: 
 
Signed:  
Date: 
 
 
Name 
Title 
 
 
 
THIS CONFIDENTIAL INFORMATION ABOUT THE INVESTIGATIONAL PRODUCT 
IS PROVIDED FOR THE EXCLUSIVE USE OF INVESTIGATORS OF THIS PRODUCT 
AND IS SUBJECT TO RECALL AT ANY TIME.  THE INFORMATION IN THIS 
DOCUMENT MAY NOT BE DISCLOSED UNLESS FEDERAL OR STATE LAW OR 
REGULATIONS REQUIRE SUCH DISCLOSURE.  SUBJECT TO THE FOREGOING, 
THIS INFORMATION MAY BE DISCLOSED ONLY TO THOSE PERSONS INVOLVED 
IN THE STUDY WHO HAVE A NEED TO KNOW, WITH THE OBLIGATION NOT TO 
FURTHER DISSEMINATE THIS INFORMATION.   
 

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TABLE OF CONTENTS 
Page 
Statement of Compliance 
2 
Signature Page 
3 
Table of Contents 
4 
Protocol Synopsis 
12 
1 
Background Information and Scientific Rationale 
17 
1.1 
Background Information ............................................................................. 17 
1.2 
BTM Previous Studies ................................................................................ 18 
1.2.1 Summary of nonclinical studies ....................................................... 18 
1.2.2 Summary of clinical trials ................................................................. 19 
1.3 
Rationale .................................................................................................... 21 
1.4 
Potential Risks and Benefits ....................................................................... 21 
1.4.1 Potential Risks ................................................................................. 21 
1.4.2 Contraindications ............................................................................... 22 
1.4.3 Precautions ........................................................................................ 22 
1.4.4 Precautions for use of BTM According to Anatomical Site ........................... 22 
1.4.4.1 Palms of hands and soles of feet .................................................... 22 
1.4.4.2 Dorsum of hands ............................................................................ 22 
1.4.4.3 Dorsum of feet ................................................................................ 23 
1.4.4.4 Face ............................................................................................... 23 

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1.4.4.5 The Neck ........................................................................................ 23 
1.4.4.6 Perineum ........................................................................................ 23 
1.4.5 Potential Benefits ............................................................................... 23 
1.4.6 Warnings ........................................................................................... 24 
2 
Objectives 
25 
2.1 
Study Objectives ......................................................................................... 25 
2.2 
Study Outcomes Measures ........................................................................ 26 
3 
Study Design 
27 
3.1   Study Population ........................................................................................... 27 
3.2 
Study Design Rationale .............................................................................. 27 
3.3 
Trial Sites ................................................................................................... 27 
3.4 
Treatment Group(s) .................................................................................... 27 
3.5 
Recruitment Period ..................................................................................... 27 
3.6 
Duration of Subject Participation ................................................................ 28 
3.7 
Outcomes ................................................................................................... 28 
3.8   Safety oversight............................................................................................. 28 
4 
Study Enrollment and Withdrawal 
29 
4.1   Subject Inclusion Criteria ............................................................................... 29 
4.2   Subject Exclusion Criteria ............................................................................. 29 
4.3   Strategies for Recruitment and Retention ..................................................... 30 
4.4   Enrollment ..................................................................................................... 30 

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4.5   Subject Withdrawal........................................................................................ 30 
4.5.1 Reasons for Withdrawal ................................................................... 31 
4.5.2 Handling of Subject Withdrawals or Subject Discontinuation of the 
Investigational Device ...................................................................... 31 
4.6   Premature Termination or Suspension of Trial .............................................. 32 
5 
Investigational Product 
33 
5.1 
Medical Device Description ........................................................................ 33 
5.1.1 Supply .............................................................................................. 33 
5.1.2 Packaging and Labeling .................................................................. 34 
5.1.3 Product Storage and Stability .......................................................... 34 
5.2 
Preparation and Administration of Investigational Device ........................... 34 
5.3 
Modification of Investigational Device for a Participant ............................... 35 
5.4 
Accountability Procedures for the Investigational Device ........................... 35 
5.5 
Assessment of Subject Compliance with Investigational Device ................ 35 
6 
Study Schedule 
36 
6.1 
Screening/Enrollment Visit #1 (Day -7 - Day 0) .......................................... 36 
6.2 
Baseline Visit #2 (Day 0) ............................................................................ 36 
6.3 
BTM ‘Take’ Visit #3 (Every 3 - 5 days from day of BTM application until 
SSG) ........................................................................................................... 37 
6.4 
SSG Visit #4 (1-2 months post BTM) .......................................................... 37 
6.5 
SSG ‘Take’ Visit #5 (7 - 10 days post SSG) ............................................... 38 
6.6 
Follow up Visits #6 - 7 (1 - 2 months post SSG) ......................................... 38 

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6.7 
Final Follow up Visits .................................................................................. 39 
6.8 
Early Termination Visit ................................................................................ 40 
6.9 
Unscheduled Visit ....................................................................................... 40 
7 
Study Procedures/Evaluations 
42 
7.1 
Study Procedures/Evaluations.................................................................... 42 
7.2 
Assessment of Concomitant Medications/Treatments/Therapies ............... 43 
7.3 
Assessment of Adverse Events/Effects ...................................................... 44 
7.4 
Laboratory Evaluations ............................................................................... 44 
7.4.1 Clinical Laboratory Evaluations ........................................................ 44 
7.4.2 Special Photographic/Video Procedures ......................................... 45 
8 
Assessment of Safety 
46 
8.1 
Specification of Safety Parameters ............................................................. 46 
8.1.1 Adverse Events ................................................................................ 46 
8.1.2 Serious Adverse Events................................................................... 46 
8.2 
Time Period and Frequency for Event Assessment and Follow-Up............ 47 
8.3 
Characteristics of an Adverse Event ........................................................... 47 
8.3.1 Causal Relationship to Investigational Device ................................. 47 
8.3.2 Anticipated SAEs ............................................................................. 48 
8.3.3 Severity of Event .............................................................................. 48 
8.4 
Adverse Event Reporting Procedures ........................................................ 49 
8.4.1 Unanticipated Problem Reporting to IRB and PPD .......................... 49 

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8.4.2 Serious Adverse Event Reporting to PPD........................................ 50 
8.4.3 Reporting of SAEs, AEs and UADEs to FDA ................................... 51 
8.4.4 Reporting of Pregnancy ................................................................... 51 
8.4.5 Reporting Device Deficiencies ......................................................... 51 
9 
Study Oversight 
53 
9.1 
Data Safety Monitoring Board (DSMB) ....................................................... 53 
9.2 
Medical Monitoring ..................................................................................... 53 
10 
Clinical Monitoring 
54 
10.1 
Site Monitoring Plan ................................................................................... 55 
11 
Statistical Considerations 
56 
11.1 
Study Hypotheses ...................................................................................... 56 
11.2 Safety Review............................................................................................. 56 
11.3 Effectiveness Review ................................................................................. 56 
11.4 Final Analysis Plan ..................................................................................... 57 
12 
Source Documents and Access to Source Data/Documents 
58 
13 
Quality Control and Quality Assurance 
59 
13.1 
Site Audits and Monitoring ............................................................... 59 
14 
Ethics/Protection of Human Subjects 
60 
14.1 
Ethical Standard ......................................................................................... 60 
14.2 
Institutional Review Board (IRB) ................................................................. 60 
14.3 
Informed Consent Process ......................................................................... 60 

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14.3.1 Consent in critical care .................................................................... 61 
14.3.2 Vulnerable populations .................................................................... 61 
14.4 
Subject Confidentiality ................................................................................ 62 
14.5 
Future Use of Stored Specimens................................................................ 62 
15 
Data Handling and Record Keeping 
63 
15.1 
Data Management Responsibilities ............................................................ 63 
15.2 
Data Capture Methods ............................................................................... 63 
15.3 
Source Documents/Types of Data .............................................................. 63 
15.4 
Schedule and Content of Reports............................................................... 64 
15.5 
Study Records Retention ............................................................................ 64 
15.6 
Protocol Deviations ..................................................................................... 64 
16 
Publication Policy 
65 
17 
Literature References 
66 
18 
APPENDICES 
69 

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List of Abbreviations 
ADL 
Activities of Daily Living 
AE 
Adverse Event/Adverse Effect 
BTM  
Biodegradable Temporizing Matrix 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hCG 
Human Chorionic Gonadotropin 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICMJE 
International Committee of Medical Journal Editors 
ICH 
International Conference on Harmonization  
ID 
Investigational Device 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
N 
Number (typically refers to subjects) 
NRS 
Numerical Rating Scale 
OHRP 
Office for Human Research Protections  
PHI 
Protected Health Information 
PI 
Principal Investigator 
PT 
Preferred Term 

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QA 
Quality Assurance 
QC 
Quality Control 
ROM 
Range of Motion 
SAE 
Serious Adverse Event/Serious Adverse Effect 
SMC 
Safety Monitoring Committee 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SSG 
Split Skin Graft 
TAKE 
BTM viability or SSG viability and acceptance 
TGA 
Therapeutic Goods Administration (Australia) 
TBSA 
Total Body Surface Area  
UADE 
Unanticipated Adverse Device Effect 
UAE 
Unanticipated Adverse Effect 
mVSS 
Modified Vancouver Scar Scale 
 
 
 

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PROTOCOL SYNOPSIS 
Study Title 
A Traditional Feasibility Study to Assess the Safety and 
Effectiveness of the Biodegradable Temporizing Matrix (BTM) 
in the Treatment of Deep Burn Skin Injuries. 
Protocol Number 
CP-002 
Study Population 
Up to 15 subjects, male and female adults (≥18 years and ≤70 
years) who have sustained deep dermal/full-thickness burn 
injuries between 10% and 70% of Total Body Surface Area 
(TBSA), will be enrolled to ensure 10 subjects are available for 
evaluation at the 3-month post Split-Skin Graft assessment. 
Study Sites 
Up to 6 US sites may participate in the study. 
Study Duration 
Approximately 20 months (includes 3 months startup and 3 
months enrollment) 
Estimated Time to 
Complete Enrollment 
6 months 
Subject Participation 
Duration  
Subjects will be on study for approximately 14 months 
Screening: approximately 1-2 days 
Treatment: approximately 2 months (from admission to 
hospital through to the end of graft ‘take’ (remains viable)) 
Follow-up: 12 months 
Description of Device 
The Biodegradable Temporizing Matrix (BTM) comprises a 
completely synthetic, sterile, integrating dermal component 
(porous biodegradable polyurethane foam) and a temporary 
epidermal barrier component (a non-biodegradable 
polyurethane sealing membrane). These layers are adhered 
with a biodegradable polyurethane bonding layer. 

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Description of Study 
Design 
This is a multi-center, single arm, traditional feasibility study to 
allow a preliminary assessment of the safety and effectiveness 
of BTM treatment. Patients with 10-70% TBSA of sustained 
burns will have BTM devices implanted in areas with deep 
partial or full thickness burns. At least 5% and a maximum of 
50% TBSA of the sustained burns will be treated. 
Study Objectives 
The Primary objectives of this clinical trial are: 
• To obtain preliminary data on the clinical safety and 
effectiveness of BTM class III medical device. 
• To assess the %BTM ‘take’ rate (%TBSA of BTM that 
has adhered at time of skin grafting, divided by the 
%TBSA treated with BTM, then multiplied by 100 to 
express as a percentage). 
•   To assess the %SSG (Split Skin Graft) ‘take’ rate 
(%TBSA of viable skin graft (taken) at day 7 - 10 post-
SSG, divided by the %TBSA of SSG applied, then 
multiplied by 100 to express as a percentage).  
The secondary objectives of this clinical trial are: 
• To assess the incidence and severity of infections in 
BTM-treated burn wounds.  
•   To assess % wound closure in BTM-treated burn 
wounds. 
• To assess the appropriateness of the study endpoints 
and the study design, including operator ease-of-use 
and subject characteristics that may impact the device 
performance. 
•   To assess the quality of wound healing in subjects 
treated with BTM, using a) the Joint Contracture 
Severity Scale, b) measurements of the Range of 
Motion (ROM), and c) scar appearance/quality using the 
modified Vancouver Scar Scale (mVSS) (Appendix 2). 

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•    To assess the incidence and severity of pruritus as 
assessed by Numerical Rating Scale (NRS) (Appendix 
2). 
Study Endpoints 
Primary Endpoints: 
• Incidence and type of adverse events occurring after 
BTM implantation. These data will be reviewed by a 
Data Safety Monitoring Board (DSMB). 
• BTM ‘take’ rate: amount of BTM that has adhered to the 
wound bed at the time of skin grafting, expressed as a 
percentage of the total amount of BTM applied.  
• SSG ‘take’ rate over BTM: applied skin graft which 
‘takes’ expressed as a percentage of the total amount of 
SSG applied at 7 -10 days after application of the SSG. 
 
Secondary Endpoints 
• Incidence and severity of infections in BTM-treated 
areas, and the success of treatment of local infections 
with BTM in place. 
• 
Clinical assessment of % wound closure. 
• Operator ease of use as determined by the physician 
survey (Appendix 2). 
• 
Joint contracture at 1, 2, 3, 6 and 12 months after SSG 
compared with baseline.  This will be assessed by Joint 
Contracture Severity Scale and Range of Motion (ROM) 
of joints (Appendix 2). 
• Scar appearance/quality in BTM -treated wounds as 
assessed using the Modified Vancouver Scar Scale 
(mVSS) (Appendix 2) at 2, 3, 6 and 12 months after 
SSG. 

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• Pruritus incidence and severity as assessed by NRS at 
SSG ‘take’ and at 1, 2, 3, 6 and 12 months after SSG 
(Appendix 2). 
Safety Assessments 
Safety will be assessed throughout the clinical trial. 
• Physical examinations will be performed at every visit. 
• Infection assessments will be performed at every visit. 
• Vital signs will be recorded at every visit. 
• Adverse events and concomitant medications will be 
recorded throughout the clinical trial. 
 
Statistical 
Approach/Rationale for 
Number of Subjects 
Continuous variables will be summarized using the 
appropriate descriptive statistics: number of observations 
(n), mean, standard deviation (SD), median, minimum, and 
maximum. Categorical variables will be summarized using 
the frequency and percentage of observed.  
Unanticipated Adverse Device Effects (UADEs), Adverse 
Events (AEs) and Serious Adverse Events (SAEs) will be 
tabulated and summarized by System Organ Class (SOC), 
preferred term (PT), severity, and relationship to study 
device.  
Sample size was determined to gain initial data, while 
minimizing risk. No formal statistical sample size 
calculations have been made.  
Data Safety Monitoring 
Board 
Study Oversight will be under the direction of a data safety 
monitoring board (DSMB).  The DSMB will operate under 
the rules of an approved charter that will be written at the 
organizational meeting of the DSMB.  The DSMB’s closed 
session will include two independent clinicians (with training 
in critical care burn surgery) and an independent 
biostatistician. For open sessions, the DSMB will also 
include the trial Principal Investigator (PI), the trial Medical 
Monitor and PNV representative(s). The DSMB will meet at 

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specific time points to assess safety and efficacy and the 
data may include: summary statistics, AE listings, vital sign 
data, local infection rate and response to treatment.  
Additionally, they will evaluate the validity of the endpoints 
and the ability of the investigators to successfully implant 
the BTM. Formal meetings of the DSMB will be conducted 
after 2 subjects complete the 7 - 10 days post SSG time 
point (collected from the time of BTM application until 7 - 10 
days after SSG application). The DSMB will meet again 
after all 10 subjects complete the 7 - 10 days post SSG time 
point and finally after all 10 subjects complete the 3 month 
post SSG follow-up visit.  All three safety and efficacy 
evaluations will guide the study design of the proposed 
pivotal trial. 
 

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1 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
1.1 Background Information 
 
Split-skin grafting has been used to treat deep burns for over 140 years. The benefits of 
this technique include: 
i. 
Application of ‘self’ (autologous) material.  
ii. 
An inosculatory capacity for rapid ‘take’ because its harvest transects 
thousands of blood vessels supplying the papillary dermis and thus (by 
diffusion) the epidermis.  
iii. 
New vessel growth (angiogenesis) from the wound bed is stimulated by 
growth factors (Vascular endothelial growth factor) from these vessels. 
iv. 
It contains some dermal supporting elements, a basement membrane and 
an intact epidermis, thus signaling after application that the wound is 
‘closed’ and that inflammation can abate.  
v. 
No material cost. 
The split skin graft technique, however, has multiple limitations. These have been largely 
overlooked because of the lack of alternatives. These disadvantages include: 
i. 
In certain populations (the elderly, for example), the dermis is thinner and 
donor site healing is impaired causing pain with recurrent breakdowns and 
repeated infections.  
ii. 
The use of the split skin graft does not replace ‘like with like’.  
iii. 
Skin grafts are thin (generally between 8 and 14 thousandths of an inch) 
and, when used to replace deep or full thickness skin loss, cannot confer 
the same degree of robustness to future mechanical, thermal or chemical 
insult.  
iv. 
Providing a reduced thickness of elastic dermis does not usually allow 
complete restitution of the supple envelope that uninjured skin provides to 
facilitate joint mobility and range.  
v. 
Without underlying dermal support the edge of the excised burn, where skin 
graft meets normal skin, is often depressed and has an obvious 
appearance.  
vi. 
Because the skin graft contains dermis, a donor site scar (however good) is 
always created.  
Some of these issues can be remediated or delayed by the use of active “temporizing 
matrices” that temporarily close the debrided burn wound, integrate and provide ‘dermal’ 
structure prior to subsequent (delayed) application of split-skin graft. This strategy has 

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been applied successfully for many years by animal-sourced collagen templates (such as 
Integra® Dermal Regeneration Template) and has allowed for the reduction of graft 
contraction and improvement in functional and cosmetic outcomes after split-skin grafting 
where burn debridement has extended deeply into fat, fascia or muscle10,11. In particular, 
a marked cosmetic improvement is observed when widely meshed graft is applied over 
the integrated matrix (compared to the unsightly, wide ‘chicken-skin’ appearance 
otherwise achieved by applying widely meshed graft on fat). Although a split skin graft 
donor site is still needed to effect permanent closure, this can be acquired serially, buying 
time for surgeon and subject.  
Collagen-based dermal matrices are underused globally, mainly because of their high 
cost12 and their biological composition and delayed neovascularization may contribute to 
an increased rate of infection13, 14. Synthetic alternatives would be expected to reduce 
cost and susceptibility to infection.  
A successful skin graft replacement strategy for extensive wound healing must thus have 
2 component parts: 1) a material capable of performing the ‘dermal integration/temporary 
physiological closure’ action for up to 4 weeks, and 2) an autologous skin product that 
can be applied over the dermis to afford permanent wound closure. 
The 
importance 
of 
this 
trial 
is 
that 
it 
will 
provide 
data 
regarding 
the 
appropriateness/applicability of the safety and efficacy outcomes (endpoints), including 
operator technique challenges and subject characteristics that will further support the 
design of a proposed subsequent pivotal, human multi-center trial of BTM when used in 
the surgical management of significant thermal burn injuries. The pivotal trial data will 
facilitate application for marketing of the BTM in the United States by the Food and Drug 
Administration (FDA) via a Pre-Market Approval pathway.  
1.2  BTM Previous Studies 
1.2.1 Summary of nonclinical studies  
An extensive laboratory, in vitro cell culture and in vivo animal research program has 
preceded this trial. The results of these studies have been published in peer-reviewed 
journals and presented at several international scientific conferences1,2,3. In addition, 
biocompatibility studies have been conducted in accordance with ISO 10993 standards.  
In vitro studies were performed using prototype versions of the BTM. These studies 
indicated compatibility of BTM with living cells. A 6-month toxicity study in rats indicated 
that the test article was well tolerated and there were no findings of toxicity, or abnormal 
clinical or abnormal histological findings related to the test article. 

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Additionally, porcine studies demonstrated that the prototype BTM foam integrated rapidly 
into full-thickness cutaneous porcine wounds, and allowed successful skin grafting over 
the integrated BTM4,5,6. These studies also demonstrated that an unsealed, 2 mm thick 
foam resulted in unacceptable wound contraction. It was concluded that the foam 
structure had to be ‘sealed’ to prevent evaporative water loss and over-deposition of 
collagen and fibroblast migration. An intermediate version of the BTM was generated with 
a sealing membrane to limit evaporative loss and resist contraction. A study to compare 
BTM 
with 
Integra® 
Dermal 
Regeneration 
Template, 
which 
is 
a 
sealed, 
collagen/glycosaminoglycan dermal matrix, was conducted in pigs5. This study 
demonstrated that identical treatment of the two materials using the same overdressing, 
resulted in a high rate of infection in the Integra® treated animals (5 of 6) and in no 
infections (0 of 6) in the BTM-treated animals. Further, after spontaneous loss of the 
Integra sealing layer, the wounds contracted aggressively. In contrast, the prototype BTM 
devices did not spontaneously lose their seal or become infected. Further studies were 
conducted to optimize the sealing membrane and bonding layer7. 
An additional long-term nonclinical toxicology study will be performed concurrently with 
this traditional feasibility trial as a regulatory requirement. 
1.2.2 Summary of clinical trials 
A pilot trial of short term, biodegradable polyurethane foam implantation as a topical 
negative pressure interface to assess tissue reaction to the presence of the material in 
human surgically debrided pressure sores has been completed and the results 
published8. No evidence of irritation, sensitivity, discomfort, itching, rash or any device-
related adverse event was observed.  
A pilot trial of long term, implantation of a prototype BTM into 10 free flap donor sites has 
also been completed in Adelaide, Australia, assessing ease of application and 
fixation/speed, completeness of integration, ease of delamination and ability of the 
integrated matrix to sustain skin graft survival to definitive closure9. This study also 
revealed no evidence of reaction to the implanted BTM foam. Biopsy of the maturing 
wounds at 6, 9, 12 and 18 months revealed progressive disappearance of the polymer 
material with infrequent microscopic remnants visible at 12 months on histology and none 
visible at 18 months. During this study, the investigators noted that the seal was fragile 
and tore during delamination, making the process of seal removal time-consuming. A new 
BTM seal and bond were developed to address this issue and assessed in the porcine 
model described in section 1.2.1. The safety findings in this study indicate a total of 10 
device-related adverse events which included blood under BTM seal (n = 3), infection 
under BTM (n =1), spontaneous delamination due to sub-seal collection (n =1), partial 
failure of BTM to integrate (16%, 24% and unknown) (n = 3), 80 – 100% spilt skin graft 
‘take’ (n = 2) and seroma (n =1), none of which were classified as serious device related 

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adverse events 
The Australian Therapeutic Goods Administration (TGA) subsequently granted three 
plastic/burn surgeons approval to use the BTM (with the new seal and bond) as an 
unapproved device for further long-term evaluation of BTM implantation into free flap 
donor sites10. Twenty-five subjects have subsequently received the BTM device with 
many of these subjects having greater than 1 year of follow up data available. In these 
subjects, the BTM seal has been hand fenestrated and this has successfully reduced sub-
seal fluid collection. BTM delamination is now rapid, in one piece and with one action. 
Device attributable adverse events collected from this study include graft failure (partial 
or full) (n = 4), spontaneous delamination (n = 3) and fluid/blood under seal (n =2).  
A prospective pilot study (ACTRN12613001375741) in Australian subjects, under the 
authority of the TGA is currently being performed with the same BTM device as the 
second in-human clinical study but with fenestrations added during manufacture (rather 
than by hand during application). This study is being conducted in subjects with deep-
dermal or full thickness burn injuries to between 20% and 50% TBSA. Five subjects have 
completed skin grafting, are being assessed for safety and effectiveness of BTM and will 
be followed for a year. Three of the 5 subjects have passed the year milestone to date. 
Results to date have shown BTM-treated areas are soft, pliable and back to normal skin 
color at the 9-month time point. Since closure of this prospective pilot study, a further 2 
subjects with larger TBSA burns have had BTM applied to up to 70% of their TBSA in 
Australia under a special access scheme. To date, these subjects have tolerated the BTM 
well with only minor sub-seal hematomas and, occasional, small localized sub-seal fluid 
collections (clinically infected but not interfering with BTM integration) reported. 
 
Although complete safety data are not yet available from the ongoing prospective pilot 
study, to date adverse events related to the device in these patients include fluid/blood 
under the seal (n = 9), infection at the BTM site (n = 1), mild delamination (n =1), BTM 
integration failure (n = 5), failure of a portion of split skin graft to ‘take’ < 1% TBSA (n =4), 
split skin graft breakdown (n =2)) and joint contracture (n =3).  Histological wound healing 
associated with BTM implantation, has demonstrated a temporal and progressive 
dissolution of the foam supporting the expected outcome of complete degradation over 
time.  
An additional clinical trial is also currently underway (CT-2015-CTN-00488-02). This is a 
prospective, non-controlled, open-label study evaluating the use BTM in the treatment of 
patients with deep burns which require excision and skin grafting. This is a 12-month 
study being performed across Australia and France for the purpose of CE Marking and 
will include 30 patients (aged 18 – 70 years) across multiple sites. Sixteen patients have 
been enrolled into this study as of 6 April 2017.  

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1.3 Rationale 
The BTM has been designed to function as an active, temporizing dermal matrix, applied 
onto deep tissues (fat, muscular fascia, muscle, tendon, etc.), exposed by the process of 
debridement of deep dermal and full thickness burn injuries. Its design function is to 
integrate into the wound bed and to produce a vascularized ‘neo-dermis’ capable of 
accepting a split skin autograft and facilitating survival of that graft to definitively close the 
wound. Its route of administration is thus implantation and fixation into an open, debrided 
wound bed. BTM will be applied to temporarily close debrided deep wounds of between 
10 and 70% of the TBSA. Given an average TBSA of 1.71m2, between 2 and 11 BTM (20 
cm x 40 cm) are needed in order to cover 5 - 50% TBSA.   
1.4 Potential Risks and Benefits 
1.4.1 Potential Risks 
Two residual risks were identified as part of the risk assessment and have been 
subsequently addressed with risk mitigations integrated into the Schedule of 
Assessments and Procedures (Appendix 1). One potential risk is unplanned 
seal/membrane removal; human data shows that the seal can stay for up to 43 days if 
required10. The second potential risk is that the skin graft may not ‘take’ due to infection, 
hematoma, or excessive shear. Clinical results show these risks are not common in either 
small surgical wounds or significant debrided burn wounds13. With other burn treatment 
devices, if infection occurs, it may require removal of the device, or a portion of the device, 
which prolongs treatment times and risks subject safety. Experience with BTM to date 
suggests that infection can be treated either topically or systemically often without 
requiring the removal of the device. It is anticipated that this may be an advantage that 
BTM has over existing matrices.   
Risk mitigations include: 
• 
A pre-specified plan for periodic subject outcome assessments and reporting prior to 
enrollment of additional subjects (e.g. the plan will be reviewed by a DSMB) 
• 
Follow-up assessments at regular intervals to monitor subject safety and device 
effectiveness 
• 
Timely reporting of serious adverse events 
• 
Timely reporting of device performance parameters, which help determine whether 
the device functions as intended (e.g. measurements of deliverability, stability, 
handling, visualization, patency, integrity) 

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• 
Principal Investigators at the clinical trial sites can receive input (verbal, written, 
photographs etc.) from experienced burn surgeons regarding BTM if AEs occur 
1.4.2 Contraindications 
 BTM is contraindicated in subjects with a known hypersensitivity to polyurethanes.  
1.4.3 Precautions 
Solution containing sodium hypochlorite (Dakin’s solution) should not come in contact 
with BTM. 
1.4.4 Precautions for use of BTM According to Anatomical Site 
1.4.4.1 Palms of hands and soles of feet 
No BTM to date has been used to primarily temporize and reconstruct glabrous skin. Due 
to the uniquely specialized structure and function of the palmar and plantar skin, 
replacement with skin grafts may lead to a poorer functional and cosmetic outcome. 
However, these areas have a high capacity for epithelialization under conservative 
management without the need for tangential debridement, even with surrounding deep 
burns. An initial conservative approach following appropriate initial antiseptic scrub 
cleaning and observation over 2 weeks allows areas refractory to conservative 
management to declare. At this time, BTM use in the glabrous skin is cautioned.  
1.4.4.2 Dorsum of hands 
Whilst affording effective temporization of the debrided burn wound, application of BTM 
on the dorsum of hands and fingers delays early mobilization of the fingers in order to 
allow the BTM to adhere. The thickness of the integrated BTM in its current form may 
also reduce the elasticity of the reconstructed skin. These properties may reduce resultant 
active and passive range of motion of the fingers, which can eventually be improved in 
the compliant and motivated patient, however primary split skin grafting to these areas 
would enable earlier return to motion exercises. At this time, BTM use in the dorsum of 
the hands is cautioned.  
 

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1.4.4.3 Dorsum of feet 
The experience to date in patients with burns to the dorsum of the feet (2 feet, one patient, 
6 months follow up) is that BTM facilitates effective temporization and robust cover over 
the extensor tendons (paratenon preserved) with good functional outcome to date. 
1.4.4.4 Face 
No BTM to date has been use to primarily temporize and reconstruct the face. Like the 
glabrous skin, limited areas of deeper burns can epithelialize effectively with conservative 
measures (soft paraffin application) due to the high vascularity and presence of skin 
appendages (glands, hair follicles).  There may be a role for secondary scar revision or 
contracture release with BTM, however, like the dorsum of the hands, the current 2 mm 
thick iteration may be too thick to offer optimal results and its potential effect on the 
position of sensitively functional structures such as the eyelids and the oral margin is 
unknown and may be detrimental (causing ectropion, poor oral mobility/competence etc). 
At this time, BTM use in the face is cautioned.  
1.4.4.5 The Neck 
To date, one patient has received BTM in the neck for early secondary contracture release 
in burns. The initial results are encouraging but medium to long term results are unknown. 
The use of BTM in the neck for primary burns reconstruction is therefore cautioned.  
1.4.4.6 Perineum 
To date, the BTM has been applied successfully to the buttocks and the thighs. It has not 
been applied to the perineum or the genital area, therefore the results are not known. The 
use of BTM in the perineum is therefore cautioned. 
1.4.5 Potential Benefits 
For moderate to large burn injuries in subjects, grafting at a second operation allows 
significant physiological recovery of the subject prior to graft harvest and application. 
Reducing the early surgical ‘insult’ to major burn injury sufferers is important in assisting 
patient survival and reduces the risk of loss of resources (such as harvested applied skin 

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grafts and skin graft donor sites) secondary to physiological insufficiency or deterioration. 
The cosmetic and functional outcomes of using commercially available dermal matrices 
before grafting are considerably better than a SSG alone13, however their composition 
(collagen/other biological materials) may increase the risk of infection. Given the potential 
for increased susceptibility to infection and the high cost of existing matrix products, their 
use is typically restricted to burns >50% of TBSA. The benefits of BTM may include 
improvements in skin function and cosmesis, and with a much more cost-effective 
material and strategy than standard dermal matrices. 
1.4.6 Warnings 
The following complications are possible with the use of BTM. If any of the following 
conditions occur, the device should be removed: chronic inflammation, allergic reaction, 
excessive redness, pain or swelling. 
BTM should only be applied onto surgically debrided wounds where underlying pathology 
capable of potentiating the wound has been addressed (e.g. meticulous blood sugar 
control in diabetic ulceration, compression hosiery/dressings in venous ulceration to 
combat sustained venous hypertension, etc.). BTM should be applied onto wounds only 
after effective haemostasis has been afforded. 
 

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2 OBJECTIVES 
2.1 Study Objectives 
The purpose of the trial is to evaluate the safety and effectiveness of the ability of the 
BTM class III medical device to satisfactorily fulfill the trial endpoints and thus evaluate 
the appropriateness and applicability of those endpoints for the subsequent pivotal trial.  
Within the confines of the trial, biodegradable polyurethane will become incorporated into 
the subjects’ wounds to form a neo-dermis. Specifically, temporization of the wound 
(prevention of contraction and infection), integration and ability to sustain split skin graft 
‘take’ will be evaluated. 
Primary Objectives: 
The primary objectives of this clinical trial are: 
• To obtain preliminary data on the clinical safety and effectiveness of BTM. 
• To assess the %BTM ‘take’ rate (%TBSA of BTM that has adhered at time of skin 
grafting, divided by the %TBSA treated with BTM, then multiplied by 100 to express 
as a percentage). 
•   To assess the %SSG (Split Skin Graft) ‘take’ rate (%TBSA of viable skin graft 
(taken) at day 7 - 10 post-SSG, divided by the %TBSA of SSG applied, then 
multiplied by 100 to express as a percentage).  
Secondary Objectives: 
The secondary objectives of this clinical trial are: 
• To assess the incidence and severity of infections in BTM-treated burn wounds. 
• To assess % wound closure in BTM-treated burn wounds. 
• To assess the appropriateness of the study endpoints and the study design, 
including operator ease of use and subject characteristics that may reflect the 
impact of the device performance. 
• To assess the quality of wound healing in subjects treated with BTM, using Joint 
Contracture Severity Scale, measurements of the Range of Motion (ROM), and 
scar appearance/quality scales using the modified Vancouver Scar Scale (mVSS) 
(Appendix 2). 

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• To assess the incidence and severity of pruritus as assessed by Numerical Rating 
Scale (NRS) (Appendix 2). 
2.2 Study Outcomes Measures 
Primary Endpoints: 
• Incidence and type of adverse events occurring after BTM implantation. This will 
also be reviewed by a Data Safety Monitoring Board (DSMB). 
 
• BTM ‘take’ rate. Amount of BTM that is viable (taken) at the time of skin grafting, 
expressed as a percentage of the total amount of BTM applied.  
 
• SSG ‘take’ rate. Applied skin graft which remains viable (‘takes’) expressed as a 
percentage of the total amount of SSG applied 7 -10 days after application of the 
SSG. 
Secondary/Exploratory Endpoints: 
• Incidence and severity of infections at the wound site, and the success of treatment 
of local infections with BTM in place. 
• Clinical assessment of % wound closure. 
• Operator ease of use as determined by the physician survey (Appendix 2). 
• Joint contracture at 1, 2, 3, 6 and 12 months after treatment compared with 
baseline. This will be assessed by Joint Contracture Severity Scale and Range of 
Motion (ROM) of joints (Appendix 2). 
 
• Scar appearance/quality in BTM -treated wounds as assessed by Modified 
Vancouver Scar Scale (mVSS) (Appendix 2) at 2, 3, 6 and 12 months after SSG. 
• Pruritus incidence and severity as assessed by NRS at SSG ‘take’ and 1, 2, 3, 6 
and 12 months after SSG. 

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3 STUDY DESIGN 
3.1   Study Population 
The study population includes severely ill subjects who have sustained life threatening 
deep burn injuries and who would usually receive Integra® dermal regeneration template, 
a similar dermal matrix, xenograft or cadaver allograft, to facilitate functional healing (i.e. 
those subjects with >10% TBSA full thickness burn injuries). However, beyond the upper 
end of this range (>70% TBSA full thickness burns), subjects with such injuries 
experience high subject mortality so that their inclusion in such a trial is not deemed 
prudent. Instead, this trial aims to recruit a minimum of ten subjects and a maximum of 
up to 15 subjects suffering deep-dermal or full thickness burn injuries to between 10% 
and 70% TBSA and who are able to provide informed consent, or have a legal 
representative who is able to make medical decisions on behalf of the subject.  
3.2    Study Design Rationale 
The proposed trial is a traditional feasibility trial to assess the appropriateness and 
applicability of the proposed BTM device outcomes and the measurement of those 
outcomes for use in a subsequent pivotal trial. Since outcomes for standard of care are 
defined at each study site, there is no plan to assess those standards of care or their 
outcomes in this trial design. 
3.3   Trial Sites 
The intention of this multicenter (up to 6 US sites) trial is to provide data for a feasibility 
assessment of the BTM medical device. 
3.4   Treatment Group(s) 
This will be a single-arm study with all feasibility trial subjects receiving BTM. A minimum 
of ten (10) subjects will be recruited.  
3.5   Recruitment Period  
Six (6) months 

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3.6   Duration of Subject Participation 
Study participation will last approximately 14 months, divided into an acute care period 
and a rehabilitation/therapy period.  
• Screening: approximately 1-2 days (within Day -7 to Day 0) 
• Treatment: approximately 2 months (from admission to hospital through to the end 
of graft ‘take’) 
• Follow-up: 12 months  
3.7   Outcomes 
Three primary and seven secondary outcomes have been chosen for this study, with a 
view to providing both subjective and objective clinical measures/data to demonstrate 
safety and effectiveness of BTM, as well as, the appropriateness and applicability of both 
the outcomes and the methods by which they are measured.  
3.8   Safety oversight  
An independent DSMB will be established to ensure unbiased oversight of the traditional 
feasibility trial. 

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4 STUDY ENROLLMENT AND WITHDRAWAL 
4.1   Subject Inclusion Criteria 
Subjects must fulfill all of the following inclusion criteria to be eligible to participate in the 
study: 
1. Provides written informed consent (directly or via legal representative) prior to any 
clinical trial procedures being performed. 
2. Willing to comply with all study procedures and expects to be available for the duration 
of the study. 
3. Male and females ≥ 18 years of age and ≤ 70 years of age.  
4. Patients with deep partial or full thickness burns (between 10% and 70% inclusive of 
their TBSA). The %TBSA will be determined using the rule of nines. For small areas 
within a particular anatomic region (as defined by the rule of nines), the rule of the 
palm may be used. Note: The electronic case report form (eCRF) and eCRF 
completion guidelines detail the localization of each burn region and corresponding 
wound size with % TBSA. 
5. Females, who are non-pregnant (i.e., has a negative urine human chorionic 
gonadotropin [β-hCG] pregnancy test at Day 0, prior to BTM being applied), non-
lactating, or are naturally postmenopausal (i.e., ≥12 months of natural spontaneous 
amenorrhea), surgically sterile, or who agrees to use effective contraceptive methods 
throughout the course of the study. Effective contraceptive is defined as: 
• Surgically sterile (bilateral tubal ligation with surgery at least 6 weeks prior to 
screening, hysterectomy, or bilateral oophorectomy) 
• Intrauterine device (IUD) in place for at least 3 months prior to use of study device 
• Abstinence (not having sexual intercourse) 
• Barrier method (condom or diaphragm) with spermicide for at least 14 days prior 
to screening and through study completion 
• Stable hormonal contraceptive for at least 3 months prior to study and through 
study completion 
4.2   Subject Exclusion Criteria 
Subjects will not be included if any one or more of the following conditions exists: 
1. Has a known hypersensitivity to polyurethane or silver-containing materials. 
2. Multiple traumas (i.e. significant traumatic injury to a solid organ in addition to skin). 

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3. Presence of a medical condition with a life expectancy of less than 12 months, such 
as advanced malignancy. 
4. Presence of a medical condition that might interfere with treatment evaluation; or 
require a change in therapy including but not limited to, significant immune deficiency, 
or skin or vascular diseases in the area of the wound. 
5. Has known or suspected pregnancy, planned pregnancy, or lactation (for female 
subjects).  
6. Has exposure to any other investigational agent within the last 6 months. 
7. Has clinically significant psychiatric illness (as determined by the Investigator). 
8. Has a condition the Investigator believes would interfere with the ability to comply with 
study instructions, or that might confound the interpretation of the study results or put 
the subject at undue risk. 
4.3   Strategies for Recruitment and Retention 
Subjects will be recruited into the clinical trial through the Investigator’s burn unit. Subjects 
may be compensated for their participation as described in the Informed Consent Form 
(ICF). Once discharged from the burn unit, subjects will be contacted as part of the 
standard of care (monthly at a minimum) by the investigational site staff to remind them 
of follow-up visits and ensuring trial compliance. 
If the recruitment rate is found to be insufficient, additional sites may be added to increase 
the rate. 
4.4   Enrollment 
After burn size, depth assessment and formulation of the immediate surgical plan, the 
subject/or legal representative will be informed about the trial. After provision of, and the 
opportunity of the subject/legal representative to read, and understand, a study 
information sheet, and after the subject/legal representative has been allowed to ask any 
questions of the Investigator, signed consent, [photographic and standard institutional 
surgical consent as applicable] will be obtained following reiteration of the trial details. 
The subject will then be screened for inclusion/exclusion criteria. If all criteria are met, the 
subject will be enrolled into the trial.  
4.5   Subject Withdrawal 
Subjects may withdraw voluntarily from the trial at any time without penalty or impact on 
their treatment or the Investigator or PolyNovo may terminate a subject's participation.  

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4.5.1 Reasons for Withdrawal 
Subjects are free to withdraw from participation in the trial at any time upon request. 
An Investigator or PolyNovo may terminate a subject’s participation in the trial if: 
• Any clinical adverse event (AE), laboratory abnormality, or other medical condition 
or situation occurs such that continued participation in the trial would not be in the 
best interest of the subject. 
• The subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further participation. 
• Inability or unwillingness to complete the trial or subject noncompliance. 
• Adverse event, which is directly attributed to the presence of the implant, where 
there is no other explanation for the effect. 
4.5.2 Handling of Subject Withdrawals or Subject Discontinuation of the 
Investigational Device 
Subjects withdrawn early due to an AE will be followed until medically stable or resolution 
of the AE.   
If withdrawal from the study is requested by the subject, prior to BTM integration (i.e. 
before Day 7 post-implantation), the BTM device can be removed and the wound bed 
closed by the application of an autologous SSG. However, ≥ Day 7 the BTM can be 
removed, but it is not recommended, as integration will likely have occurred to a point 
such that BTM removal would result in damage to the subject’s burn wound. In either 
case, no data or BTM -related follow-up will be imposed. Physicians are expected to follow 
subjects according to their institution’s standard of care. Investigational Device Exemption 
(IDE) regulations require investigators to maintain each subject’s case history and 
exposure to the device. 
All consented subjects who have been implanted with BTM, even in the event of device 
failure, will have all lesions followed up as a part of the study until completion or if/when 
withdrawal from the study is requested by the subject.  
If subjects do not complete 3 months follow up post SSG implantation for any reason, 
they will be replaced with further subjects that meet the inclusion/exclusion criteria, to  

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ensure that the final cohort is (a minimum of) 10 subjects. 
In case of withdrawal, the Investigator will promptly inform the Institutional Review Board 
(IRB) within 5 working days and will provide the reason(s) for the withdrawal.  All 
applicable source documentation will be collected to confirm resolution.  
4.6   Premature Termination or Suspension of Trial  
This trial may be suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for trial suspension or termination, 
will be provided by PolyNovo and agreed upon by the DSMB. If the trial is prematurely 
terminated or suspended, the Investigator is responsible for promptly informing subjects 
and the IRB with the reason(s) for the termination or suspension.  
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unanticipated, significant, or unacceptable risk (e.g. serious 
adverse device effect) to subjects 
• Insufficient adherence to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
Halting rules will be included in the DSMB Charter and Statistical Analysis Plan. 

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5 
INVESTIGATIONAL PRODUCT 
5.1 
  Medical Device Description 
BTM is a fully synthetic biodegradable dressing that is composed of three layers. 
• Dermal component: A 2 mm thick, white, open cell, degradable polyurethane foam 
(pore sizes of 100-600 µm) with a high degree of porosity (~94%) providing a scaffold 
for dermal tissue integration  
• Epidermal component: A temporary bonding layer designed to adhere the sealing 
polyurethane film/membrane (65 µm thick) to the dermal foam 
• Membrane: A temporary 50 μm thick, transparent, fenestrated, polyurethane sealing 
membrane designed to physiologically close the wound and limit evaporative water 
loss 
BTM is indicated for primary dermal repair after excision of deep dermal and full thickness 
thermal burn injury in adults. Usually such definitive epidermal closure is provided by skin 
autograft. BTM is designed to be implanted into the newly created wound bed and stapled 
or sutured to the edge of the wound. The BTM provides a scaffold to facilitate dermal 
repair whilst keeping the wound physiologically ‘closed to reduce wound contraction’. 
After integration, the combined bonding layer and sealing membrane is peeled off and 
discarded, leaving only the implanted foam layer to biodegrade. The timing of the de-
lamination is at the discretion of the Investigator based on his/her clinical and surgical 
judgement. Past clinical experience has placed this de-lamination between Days 21–56, 
but can be extended beyond 56 days if required. The wound bed is refreshed (e.g. by 
dermabrasion) and finally closed with a thin SSG. 
5.1.1 Supply 
All component parts of the BTM are manufactured, assembled packaged and pre-
sterilized by PolyNovo Biomaterials Pty Ltd, Port Melbourne, Victoria, Australia. The 
facility is ISO 13485 compliant and audited to the requirements of 21 CFR Part 820. The 
investigational device will be supplied to the investigating sites through a product depot 
vendor.  
The proposed device is intended to be supplied in various sizes, including 20 cm × 10 
cm, and 20 cm × 40 cm. The devices supplied for this trial will be 20 cm × 40 cm. The 
dressings are single use, terminally sterilized devices (by gamma-irradiation at 25kGy) 
that are individually packed in a polymer pouch within an aluminized envelope for 

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moisture resistance. The packaging is designed to be opened in a surgical setting so as 
to preserve the sterility of the operating field. 
5.1.2 Packaging and Labeling 
The BTM device is dry-packed in multilayered, hydration-proof packaging and labeled 
with details which uniquely identify the product including: date of manufacture; date of 
expiration; lot number; reference number; and manufacturer information. Labels are 
affixed to outer foil packaging. The label should be retained for the subject’s source 
records.  
5.1.3 Product Storage and Stability 
The packaged BTM can be stored vertically or flat on a shelf in a secure location. There 
are no special storage requirements (e.g. temperature) although perforation of the 
packaging during storage or transport should be avoided as this will void sterility if 
penetration of the inner packaging occurs. The shelf life of the device is three (3) years. 
The device should not be used if the inner packaging has been opened, or obviously 
tampered with. If the inner packaging is found to be open, report and send the package 
as found back to PolyNovo. 
5.2   Preparation and Administration of Investigational Device 
The sole investigational device in this traditional feasibility trial is the BTM. It is supplied 
with the seal factory-fenestrated and in pieces 20 cm × 40 cm. These can either be cut to 
size (for smaller wounds) or joined side-to-side (not overlapped) by stapling at seams (in 
large wounds). No special preparation of the BTM is necessary. It is removed from the 
outer packaging using sterile technique and opened from one end of the inner packaging 
to preserve the operating field. Full instructions are available in the Site Manual of 
Operations. Once opened, the BTM must be used or discarded and cannot be re-stored. 
The BTM device is not intended to be used on the hands, face, neck, plantar skin, or 
perineal area. See Section 1.4.3 for detailed precautions. 
Previous clinical use of BTM has demonstrated that integration rate of BTM and primary 
skin graft ‘take’ is decreased when BTM is used over bony prominences (such as the 
olecranon, spine of scapula, calcaneus), as pressure may inhibit integration. Standard 
pressure area precautions should be taken to ensure successful integration of BTM. In 
previous clinical use, BTM has been delaminated between Days 21 and 56 after 
implantation and this range will serve as a guide for this study. The timing of the de-

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lamination is at the discretion of the Investigator based on his/her clinical and surgical 
judgement and could extend beyond 56 days if required. 
 
5.3   Modification of Investigational Device for a Participant 
The number of BTM devices required by an individual subject depends on the size of the 
excised burn wound (between 10 and 70% of the total body surface area). In this 
traditional feasibility trial, subjects with deep partial or full thickness burns will have BTM 
devices implanted on at least 5% and a maximum of 50% of their TBSA of the sustained 
burns to be treated. This maximum is based on clinical experience to date treating burn 
areas with BTM (1% to 63% TBSA) (unpublished data of ongoing subjects). 
 
5.4   Accountability Procedures for the Investigational Device 
PolyNovo’s designee, PPD, will distribute, track and account for all investigational 
devices. Instructions for the investigational device return and/or destruction will be 
provided in the Site Manual of Operations. 
5.5   Assessment of Subject Compliance with Investigational Device  
The BTM is directly visualized every three to four days during dressing changes until skin 
graft ‘take’. Inspection of the sealing membrane and of BTM integration is performed 
during dressing changes for both inpatient and outpatient subjects. The ‘take’ assessment 
occurs after the sealing membrane is removed.  As subjects with severe burns are 
typically confined to hospital under supervision, compliance has not been a problem in 
similar study populations in pilot studies. After skin graft ‘take’, no compliance issues have 
occurred to date.  

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6 STUDY SCHEDULE 
6.1 Screening/Enrollment Visit #1 (Day -7 - Day 0) 
• Obtain and document informed consent from potential subject/legal representative 
prior to any study-related procedures being conducted.    
• Obtain demographics and review medical history.  
• Obtain completion of the Fitzpatrick Skin Typing Test when the subject is able. 
This is to be completed once from the Screening visit up to and including Visit 6 (1 
month post SSG follow-up visit) 
• Preliminary review of subject eligibility based on inclusion/exclusion criteria  
• Perform full physical examination (and full burn assessment including burn size 
(%TBSA), depth of burns, and applicable x-rays), record of vital signs, weight and 
height. 
• Review concomitant medications and medication history. 
• Assessment of any infection (A clinical diagnosis supported by confirmatory 
laboratory findings).  
• Assessment of adverse events. 
6.2   Baseline Visit #2 (Day 0) 
• Perform full physical examination (and full burn assessment including burn size 
(%TBSA), depth of burns and applicable x-rays) with the recording of vital signs. 
• Review concomitant medication(s) history. 
• Urine pregnancy test (applicable females). 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Final review of inclusion/exclusion criteria to determine subject eligibility, prior to 
application of BTM.  
• Under anesthesia, the subject’s burn wounds will be excised and debrided.  While 
maintaining hemostasis, the BTM will be applied. 

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• Assessment of joint contracture severity and ROM of affected joints.  
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
6.3   BTM ‘Take’ Visit #3 (Every 3 - 5 days from day of BTM application until SSG)  
• Perform full physical examination with recording of vital signs results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Assessment of adverse events. 
• Assessment of BTM integration and examination for signs of incomplete 
spontaneous delamination. 
6.4   SSG Visit #4 (1-2 months post BTM) 
• Perform full physical examination with recording of vital signs and record results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Determine BTM integration (‘take’) rate. This is a visual assessment of the amount 
of BTM that has integrated (‘taken’) at the time of SSG, expressed as a percentage 
of the total amount of BTM applied. Integration is the process where new blood 
vessels grow into the foam. As it progresses, the foam becomes populated with 
adipocytes and fibroblast and later blood vessels and blanching or capillary refill 
may be demonstrated through the seal. 
• ‘Take’ is determined post de-lamination (i.e., following the sealing membrane 
removal.  
• When donor sites are available, the BTM is integrated and it is physiologically 
optimal for the subject, the BTM device will be delaminated (sealing membrane 
removed) and a SSG applied which may be meshed (as per surgeon’s preference) 
applied, closed and dressed. Patients can be outpatients prior to skin graft. 

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Please note: The Investigator will determine when integration is complete. After 
integration, the combined bonding layer and sealing membrane is peeled off and 
discarded, leaving only the implanted foam layer to biodegrade. The timing of the 
de-lamination is at the discretion of the Investigator based on his/her clinical and 
surgical judgement. Past clinical experience has placed this de-lamination 
between Days 21-56, but can be extended beyond 56 days if required. 
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
• Burn surgeon will complete the Physician’s Survey (Appendix 2) 
6.5   SSG ‘Take’ Visit #5 (7 - 10 days post SSG)  
• Perform full physical examination with recording of vital signs and record results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Determination of %Split Skin Graft (SSG) adherence/integration (‘take’) rate. 
Calculated as the proportion of the SSG which remains viable (‘takes’) over area 
where BTM Burn was applied (post de-lamination or seal removal), expressed as 
a percentage of the total amount of SSG applied over BTM at 7 -10 days after 
application of the SSG. 
• Assessment of pruritus using the NRS.  
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
6.6  Follow up Visits #6 - 7 (1 - 2 months post SSG) 
• Perform full physical examination (and full burn assessment including size 
(%TBSA) and depth of burns and applicable x-rays) with recording of vital signs, 
and record results. 
• Review concomitant medication(s) history. 

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• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Assessment of joint contracture severity and ROM of affected joints 
• Assessment of % wound closure. 
• Assessment of scar appearance/quality using the mVSS. 
• Assessment of pruritus using the NRS. 
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
6.7  Final Follow up Visits  
The following assessments will be performed at Visit 8, 11 and 17 (3, 6 and 12 months’ 
post SSG):  
• Perform full physical examination with recording of vital signs, weight, and urine 
pregnancy test (applicable females) and record results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Assessment of joint contracture severity and ROM of the affected joints. 
• Assessment of % wound closure. 
• Assessment of scar appearance/quality using the mVSS. 
• Assessment of pruritus using the NRS. 
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
A follow-up phone call will be performed at Visit 9 and 10, and Visits 12 to 16 (4, 5 and 7 
to 11 months’ post SSG) to collect AEs and changes to concomitant medications.  

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6.8   Early Termination Visit 
• Perform full physical examination with recording of vital signs, weight, and urine 
pregnancy test (applicable females) and record results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Assessment of joint contracture severity and ROM of the affected joints. 
• Assessment of % wound closure. 
• Assessment of scar appearance/quality using mVSS. 
• Assessment of pruritus using the NRS. 
• Assessment of adverse events. 
• Photographs of areas where BTM was implanted. 
6.9   Unscheduled Visit  
Unscheduled visits will only be recorded if the subject has: 
a. Missed a scheduled appointment/visit and the Investigator wishes to have a time-
point appraisal done in a delayed fashion, or 
b. Has developed problems/issues requiring investigation/evaluation. 
Assessments include: 
• Perform full physical examination with recording of vital signs, weight, and urine 
pregnancy test (applicable females) and record results. 
• Review concomitant medication(s) history. 
• Assessment of any infection (BTM or non-BTM related) (A clinical diagnosis 
supported by confirmatory laboratory findings).  
• Assessment of joint contracture severity and ROM of the affected joints. 
• Assessment of % wound closure. 

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• Assessment of scar appearance/quality using mVSS. 
• Assessment of pruritus using the NRS. 
• Assessment of adverse events. 
• Photographs will be taken. 

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7 STUDY PROCEDURES/EVALUATIONS 
7.1 Study Procedures/Evaluations 
• Medical history including concomitant and medication history will be collected and 
recorded. 
A 
review 
of 
permitted 
and 
prohibited 
medications 
per 
Inclusion/Exclusion (I/E) criteria will be performed and demographic data recorded.  
Demographic data will be collected. 
• The Fitzpatrick Skin Typing Test, as detailed in Appendix 220, will be collected 
when the patient is able. 
• Full Physical examination to include the following organ systems: skin, head, eyes, 
ears, nose, throat, neck (to include lymph nodes), back, chest, lungs, heart, 
abdomen, gastrointestinal tract, legs, musculoskeletal system, neurologic, and 
vascular system will be conducted at all visits. Height and weight will be recorded 
only at Visit 1 (-7 to Day 0) for TBSA calculation. Weight will be recorded at follow-
up visits and early termination.  
• A full burn assessment including burn size (%TBSA) by region, depth of burns, % 
of BTM applied and x-rays (where applicable) will be conducted. All burn 
assessments (Appendix 2 including: ROM, mVSS, and NRS) will be conducted 
per burn wound region/site. NOTE: The Maximum BTM that may be applied is 
50% of the TBSA. 
• Vital signs [blood pressure (supine), respiratory rate, pulse, and temperature] will 
be assessed to ensure subject meets eligibility for trial enrollment and will be 
conducted at all subsequent visits.   
• Clinical Assessment of any infection will be performed using institutional standard 
of care procedures. Microbiological assessment of infection will only be performed 
if there is clinical suspicion of infection or if routine surveillance swabs are part of 
the institutional standard of care for subjects with severe burns. 
• Evidence of BTM integration (adherence, color, loss of foam pattern, 
vascularization [illustrated by capillary blanching with pressure and refill when 
pressure released]) will be assessed every 3-5 days until SSG procedure. Patients 
can be outpatients prior to skin grafting. 
• An assessment of the %BTM ‘take’ rate will be measured by the %TBSA of BTM 
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with the BTM device and multiplied by 100 to express as a percentage (Section 
11.3). 
• An assessment of the %SSG ‘take’ rate will be measured by the amount of applied 
skin graft which remains viable (‘takes’) expressed as a percentage of the total 
amount of SSG applied at 7 -10 days after application of the SSG (Section 11.3).  
• An assessment of the quality of the wound will be measured using active Range 
of Motion (ROM) of affected joints when possible and severity of joint contracture 
(Appendix 2). The details regarding the assessment of the grading for mild, 
moderate and severe contractions are also included in Appendix 2.  
• An assessment of % wound closure for each BTM-treated burn wound. 
• Scar appearance/quality will be assessed using the modified Vancouver Scar 
Scale (mVSS) (Appendix 2). 
• Pruritus incidence and severity will be assessed by the Numerical Rating Scale 
(NRS) (Appendix 2). [The eCRF will also capture duration, NRS scale (intensity), 
disability, and distribution on the body.] 
• Physicians will be surveyed to assess Ease of Use. The eCRF will capture ease 
of BTM application, delamination, time, and overall impressions. 
• Subjects will be called monthly to collect adverse events and changes to 
medications and any non-trial visits with a physician regarding their burn or burn 
treatment (specify physician type: general practitioner, physical therapist, other: 
specify). 
7.2  Assessment of Concomitant Medications/Treatments/Therapies 
There is no restriction on administration to the subject of their usual medication, or such 
pharmaceutical treatments felt necessary by the Investigator such as antibiotics or topical 
aqueous only antimicrobial solutions.  
Cessation or continuation of pre-existing anti-platelet or anticoagulation treatment in 
patients with indwelling vascular stents, atrial fibrillation or prosthetic heart valves, for 
example, is to be determined by the treating surgical team according to local perioperative 
guidelines. Likewise, thromboprophylaxis measures, including chemoprophylaxis with 
low molecular weight heparin, for example, is not restricted by the use of the BTM, and 
should follow the local guidelines or Surgeon’s preference.  

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Any perioperative event indicating the commencement of a course of anticoagulation or 
antiplatelet medication is not contraindicated by use of BTM, however, as with any large 
acute surgical wound, resultant haematoma formation under the BTM should be 
anticipated as a complication and the surgical team should remain vigilant for this at 
dressing changes. This may necessitate removal and replacement of the involved section 
of BTM. 
There is no restriction on administration to the subject of additional therapies required to 
aid wound healing (including, but not limited to, occupational therapy, scar therapy, and 
physiotherapy) and should be commenced as per local standard of care guidelines. 
7.3  Assessment of Adverse Events/Effects 
Adverse events and adverse effects will be assessed at each visit. 
7.4  Laboratory Evaluations 
7.4.1 Clinical Laboratory Evaluations 
There are no specific laboratory investigations for this traditional feasibility trial. All clinical 
laboratory evaluations will be managed by the site according to standard of care, except 
safety laboratory tests. 
Safety Laboratory Tests 
In women of childbearing potential, a urine sample will be collected to test for -HCG to 
exclude pregnancy. The pregnancy test will be performed on Day 0 (Visit 2) prior to device 
implantation and results must be available prior to administration of investigational device. 
Urine pregnancy test will also be performed at 3, 6 and 12 month Post SSG visits. 
Efficacy Laboratory Tests 
NA 
Burn-specific evaluations at the discretion of the treating Investigator may include: 
Hematology:  hemoglobin, hematocrit, white blood cells (WBC) with differential count, 
platelet count. 
Biochemistry:  creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST). 

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Urinalysis:  dipstick urinalysis, including protein, hemoglobin and glucose; if dipstick result 
is abnormal, complete microscopic urinalysis is required. 
Microbiology:  blood cultures, wound swab, discharge/exudate, device or tissue  
7.4.2 Special Photographic/Video Procedures 
Digital photographs and if attainable, video footage of specific results, will be collected at 
Visit 2, Visits 4 and 5, Visits 6 to 8, Visit 11, Visit 17, Unscheduled Visit and Early 
Termination (ET) Visit with a digital camera provided by the Sponsor. Special instructions 
for the acquisition, timing, file preparation, handling, and storage of digital images will be 
included in a separate Manual of Operations. 
At each visit requiring digital photographs, clinical sites are to capture photographs of 
each burn lesion before and after the BTM device implantation (as applicable), as well as 
before and after split skin grafting and throughout wound closure. Photography is also 
part of the study design to capture potential issues with the burn wound(s).  De-lamination 
is only to be photographed (before and after) to document adverse events or other device 
issues. Investigators are encouraged to take images to support the standard of care and 
the data capture requirements of the trial.   
Please refer to the Manual of Operations for photography specifications. 

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8 ASSESSMENT OF SAFETY 
Subjects will be monitored throughout the clinical trial for adverse events/effects.  
Subjects will be instructed on the need to inform the Investigator and/or clinical trial staff 
of any AEs that may occur at any time during the clinical trial.  
Adverse events considered related to the investigational device (ID), as judged by a 
medically qualified Investigator or PolyNovo, will be followed either until resolution or the 
event is considered medically stable. 
It will be left to the Investigator’s clinical judgment to decide whether or not an AE is of 
sufficient severity to require the participant’s removal from treatment, prior to Day 7 after 
BTM implantation. A participant may also voluntarily withdraw from treatment until Day 7 
after BTM implantation without giving a reason. In either event, a Termination visit 
assessment will be performed. In the event of AE termination by the Investigator, the 
subject will be given appropriate medical care until symptoms cease, or until the condition 
becomes stable. 
8.1 
Specification of Safety Parameters 
The following information will be recorded in the eCRF for all Adverse Events:  
description, date/time of onset and end date, severity, assessment of relatedness to the 
ID, other suspect drug or device, and action taken. Follow-up information should be 
provided until resolution or as appropriately deemed by the Investigator.   
8.1.1 Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the 
research, whether or not it is considered related to the subject’s participation in the 
research. 
8.1.2 Serious Adverse Events 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 

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• Is life-threatening (places the subject at immediate risk of death from the event as 
it occurred) 
• Results in subject hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect   
• An important medical event that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, the event may jeopardize the subject and may require medical 
or surgical IP to prevent one of the outcomes listed in this definition. 
8.2 
Time Period and Frequency for Event Assessment and 
Follow-Up 
Adverse events, SAEs will be recorded in the data collection system throughout the trial 
and the subject followed until resolution or they are considered medically stable.  
The PI will record all adverse events with start dates occurring any time after informed 
consent is obtained until 7 days (for AEs) or 30 days (for SAEs) after the last day of trial 
participation. At each visit, the Investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or 
stabilization. 
8.3 
Characteristics of an Adverse Event 
8.3.1 Causal Relationship to Investigational Device 
To assess a causal relationship of an event to trial ID, the following guidelines are 
applicable: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the ID. 
b. There is a temporal relationship between the ID and event onset. 
c. The event abates when the ID is discontinued. 

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d. The event reappears upon a re-challenge with the ID. 
2. Not Related (Unlikely, Not Related) 
e. There is no temporal relationship between the IP and event onset. 
f. An alternative etiology has been established. 
8.3.2 Anticipated SAEs 
The PPD Medical Monitor in consult with the PI will be responsible for determining 
whether an SAE is anticipated or not anticipated.  A serious adverse event will be 
considered not anticipated if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described in the IB.   
8.3.3 Severity of Event 
The Common Terminology Criteria for Adverse Events v4.03 or higher (CTCAE) will be 
used to assess the causal relationship of AEs to the ID. Grades 1-5 are defined below: 
1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
2. Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL)*. 
3. Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL**. 
4. Life-threatening consequences; urgent intervention indicated. 
5. Death related to AE. 
Activities of Daily Living (ADL) 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 

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8.4 
Adverse Event Reporting Procedures 
8.4.1 
Unanticipated Problem Reporting to IRB and PPD 
Incidents or events not described in the Investigators Brochure are considered 
unanticipated.  Investigators should include the following information when reporting an 
adverse event, or any other incident, experience, or outcome as an unanticipated problem 
to the IRB: 
• appropriate identifying information for the research protocol, such as the title, 
Investigator’s name, and the IRB project number; 
• a detailed description of the adverse event, incident, experience, or outcome;  
• an explanation of the basis for determining that the adverse event, incident, 
experience, or outcome represents an unanticipated problem;  
• a description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported 
using the following timeline:   
• Unanticipated problems that are SAEs will be reported to the PolyNovo within 24 
hours and to the IRB within 1 week of the Investigator becoming aware of the 
event.  
• Any other unanticipated problem will be reported to PolyNovo within 1 week and 
to the IRB within 2 weeks of the Investigator becoming aware of the problem.  
• All unanticipated problems should be reported to appropriate institutional officials 
(as required by an institution’s written reporting procedures), the supporting 
agency head (or designee) within one month of the IRB’s receipt of the report of 
the problem from the Investigator as applicable. 
• Unanticipated adverse device effect (UADE) is defined as “any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death, was not previously 
identified in a nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other 

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unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects” (21 CFR 812.3). 
• An evaluation of a UADE must be conducted immediately and the results of the 
evaluation reported to the FDA, the IRB, and all participating investigators within 
10 working days after the sponsor first receives notice of the effect (21 CFR 
812.46(b), 812.150(b)(1)).  
All unanticipated problems will be reported to the centralized reporting system: 
24 Hour Product Safety Fax Hotline (US): XXXXXXXXXXXXX or XXXXXXXXXXX 
General questions about SAE reporting can be directed to the PPD Safety Hotline 
(available 8:00AM – 5:00PM Eastern Time):   
US:  XXXXXXXXXXXX 
8.4.2 
Serious Adverse Event Reporting to PPD 
Any AE meeting the Serious Adverse Event criteria specified below: 
1. In the view of either the Investigator or PolyNovo, the adverse events results in 
any of the following outcomes:  
a. Death 
b. A life-threatening adverse event if, in the view of either the Investigator or 
PolyNovo, its occurrence places the subject or subjects at immediate risk 
of death. It does not include an adverse event or suspected adverse 
reaction that, had it occurred in a more severe form, might have caused 
death 
c. Inpatient hospitalization or prolongation of existing hospitalization 
d. Persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or  
e. A congenital anomaly/birth defect 
f. 
An important medical event, according to FDA 21 CFR Part 312, Section 32 
may not result in death, be life-threatening, or require hospitalization may 
be considered a serious adverse drug experience when, based upon 
appropriate medical judgement, they may jeopardize the patient or subject 

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and may require medical or surgical intervention to prevent of the outcomes 
listed in this definition.  
2. Suspected - reasonable possibility that the device caused the adverse event 
3. Unanticipated - the event is not described in the Investigator brochure or is not 
listed at the specificity or severity that has been observed 
will be submitted on an AE/SAE form to PolyNovo’s centralized safety system via PPD 
Product Safety/Pharmacovigilance electronic data capture system (includes initials and 
follow-ups). The investigator is also responsible for submitting any supporting source 
documentation to the safety fax line below. 
SAE Reporting Contact Information:  
24 Hour Product Safety Hotline Fax Line (US): XXXXXXXXXXX or XXXXXXXXXX 
General questions about SAE reporting can be directed to the PVG safety hotline: XXXX 
XXXXXX (available 24/7) 
The Investigator/co-Investigator will complete a Serious Adverse Event Form and submit 
via electronic data capture within the following timeline:   
• All SAEs whether related or unrelated, anticipated or unanticipated will be recorded 
on the SAE Form and submitted to Product Safety within 24 hours of site 
awareness.  
8.4.3 
Reporting of SAEs, AEs and UADEs to FDA 
PolyNovo complies with 21 CFR Part 312 and Part 812 for mandatory reporting of safety 
events to the Food and Drug Administration (FDA). 
8.4.4 
Reporting of Pregnancy 
Any pregnancy and spontaneous miscarriage occurring during the clinical trial and the 
outcome of the pregnancy should be recorded and followed up for congenital abnormality 
or birth defect, at which point it would fall within the definition of “serious”.  
8.4.5 
Reporting Device Deficiencies 
Immediate notification by telephone will be made to the CEO of PolyNovo of any device 
deficiency. The defective material will be replaced in its wrapper and kept for transport to 
PolyNovo for critical analysis. A second material will be utilized for the surgery. If all 

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materials are found to be defective, the donor site wound will be closed with an autologous 
split skin graft and the subject will be withdrawn from the trial. 
PolyNovo Biomaterials Pty Ltd, 2/320 Lorimer Street, Port Melbourne 3207, Victoria, 
Australia.  
Phone: XXXXXXXXXXX  
Phone: XXXXXXXXXXXXX  
Email: XXXXXXXXXXXXXXXXXXX 

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9 STUDY OVERSIGHT 
9.1   Data Safety Monitoring Board (DSMB) 
Study oversight will be under the direction of a data safety monitoring board (DSMB).  The 
DSMB will operate under the rules of an approved charter that will be written at the 
organizational meeting of the DSMB.  The DSMB’s closed sessions will be composed of 
two independent clinicians (with training in critical care burn surgery) and an independent 
biostatistician. For open sessions, the DSMB will also include the trial PI, the trial Medical 
Monitor and PNV representative(s). The DSMB will meet at specific time points to assess 
safety and efficacy data. They will review the safety data that may include: summary 
statistics, AE listings, vital sign data, local infection rate and response to treatment. 
Formal meetings of the DSMB will be conducted after 2 subjects complete the 7 - 10 days 
post SSG time point (collected from the time of BTM application until 7 - 10 days after 
SSG application). Based on the data and safety reviews, the DSMB will determine 
whether to authorize enrollment of the remaining subjects.The DSMB will meet again after 
all 10 subjects complete the 7 - 10 days post SSG time point (from the time of BTM 
application until 7 - 10 days after SSG application) and after all 10 subjects complete the 
3 month post SSG follow-up visit. The DSMB will perform no further reviews during the 
treatment period unless a serious adverse device-related event occurs. In collaboration 
with the Investigator, the DSMB will also assess safety of study procedures in the protocol 
in individual subjects. At this time, each data element that the DSMB needs to assess will 
be clearly defined.  The DSMB will advise PolyNovo of its findings in a written report. 
9.2   Medical Monitoring 
It is the responsibility of the PI to oversee the safety of the trial. This safety monitoring will 
include careful assessment and appropriate reporting of adverse events as defined in 
Section 7, as well as the construction and implementation of a site data and 
safety-monitoring plan (see Section 13.1, Site Audits and Monitoring). Medical monitoring 
will include a regular assessment of the number and type of serious adverse events. 

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10 CLINICAL MONITORING 
This trial will be monitored according to an approved Monitoring Plan based on the 
objectives, purpose, design and complexity of the trial. The Investigator will allocate 
adequate time for all monitoring visits and between visits to facilitate the requirements of 
the study and study timelines.  The Investigator will also ensure that the monitor or other 
compliance or quality assurance reviewer is given direct access to all study-related 
documents and study related facilities (e.g. pharmacy, diagnostic laboratory, etc.), phone, 
fax and internet and has adequate space to conduct the monitoring visit. 
Site monitoring is conducted to ensure that the rights of human subjects are protected, 
that the trial is implemented in accordance with the protocol and/or other operating 
procedures, and that the trial uses high quality data collection processes. The monitor will 
evaluate study processes based on PolyNovo or designee standards, ICH E6 and all 
applicable, regulatory guidelines.  
Clinical monitoring includes the following visit types: 
•  Pre-Study Qualification - of the Investigator, the investigational site, staff, and 
facility. Monitors ensure the latest version of the approved protocol for the trial is 
available for review and discussion, handling of Informed Consent Forms (ICF), 
processes for AE and SAE reporting and contact information, CRF completion and 
maintenance, source documentation requirements, and ID accountability 
requirements. 
• Initiation - of the investigational site to formally begin the clinical trial. Monitors 
review goals, obligations, protocol procedures (with particular attention to 
inclusion/exclusion criteria, enrollment goals, adverse event definitions, primary 
efficacy variables and GCP compliance), informed consent procedure, AE/SAE 
reporting, CRF completion, error correction and the need for adequate source 
documentation, maintenance of the investigational binder and site visit log, status 
of ID and requirements for accountability, and any other issue as deemed 
important to the conduct of the trial. 
• Interim - monitors review AE/SAE reporting, CRF completion, error correction 
and the need for adequate source documentation, maintenance of the 
investigational binder and site visit log, status of ID and requirements for 
accountability, and any other issue as deemed important to the conduct of the trial. 

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• Close-out - monitors conduct a complete review of the Investigator site files to 
ensure that all necessary CVs are present and current, all applicable versions of 
the protocol are present and filed appropriately, all applicable versions of the ICF 
are present, IRB approval letters are present, all SAEs have been reported to 
PolyNovo and the IRB, documentation of submission of protocol deviations to the 
IRB and PolyNovo are present, notification and/or final report to the IRB present, 
a copy of the monitoring log is obtained, a copy of the Delegation of 
Responsibilities log is obtained, all CRFs have been completed and appropriately 
filed, ID reconciliation records are completed and appropriately filed, ID shipment 
and return invoices are present and appropriately filed, maintenance and retention 
of trial records are discussed, regulatory agency  inspection process is discussed. 
10.1 
Site Monitoring Plan 
A comprehensive and stand-alone monitoring plan will be established, which will ensure 
subject safety is maintained and quality data is obtained. The monitoring plan will 
emphasize the level of review for all subjects ensuring that human subject protection and 
trial procedures are of the highest quality and meet the protocol requirements, it will 
include source documents expected to be reviewed e.g. charts, lab data, photographs.  
The plan will delineate completion of the electronic case report forms (eCRFs), timely 
query resolution, definition and classification of a protocol deviation/violation, correct 
documentation of the study, device accountability, management and issue resolution, site 
communication and training. The monitoring plan will also define types of visits and 
frequency of monitoring, whether they are on-site monitoring activities or remote 
monitoring (e.g. Risk Based Monitoring) and institute strong quality control measures. 

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11 STATISTICAL CONSIDERATIONS 
Continuous variables will be summarized using the appropriate descriptive statistics: 
number of observations (n), mean, standard deviation (SD), median, minimum, and 
maximum. Categorical variables will be summarized using the frequency and percentage 
of observed data. All tabulated data will also be presented in subject level listings as 
source data. In general, no inferential statistics are to be performed due to the small 
sample size unless specified otherwise in the statistical analysis plan. 
11.1 
Study Hypotheses 
No statistical hypothesis is specified for this study as this is a feasibility study with 
approximately 10 subjects and there is no between-treatment comparison. 
11.2      Safety Review  
Adverse events will be coded using the MedDRA Dictionary (December 2015 or later) 
and severity using Common Terminology Criteria for Adverse events (CTCAE) version 
4.03 or higher. The number and percentage of subjects experiencing at least one AE will 
be presented by System Organ Class (SOC) and Preferred Term (PT). Separate 
summaries will be provided for all AEs, device related AEs, Serious AEs (SAE), AEs 
leading to withdrawal and AEs leading to death.  
The frequency and severity of infections and recurrence of infections will be tabulated. 
Clinical evaluation of erythema (redness), edema (swelling) and pain will be presented in 
a listing for all subjects and visits.   
Vital signs (blood pressure (supine), respiratory rate, pulse, height, weight and 
temperature) will be summarized by visit and presented in a listing. 
Physical examination data collected at each visit will be presented in a listing.  
11.3      Effectiveness Review 
BTM /integration ‘take’ rate is measured at time of skin grafting and is defined in the 
formula below: 
Effectiveness for %BTM ‘take’ rate and %SSG ‘take’ rate will be calculated 7 - 10 days 
after application of SSG and are defined in the formulas below:   
 

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%BTM ‘Take’ rate =  
(%TBSA covered by BTM that has adhered at time of SSG
%TBSA treated with BTM 
) × 100 
%SSG ‘Take’ rate =  
(%TBSA of viable SSG applied over BTM  
%TBSA treated SSG
) × 100 
Baseline range of motion (ROM) of joints (evaluated immediately after eschar removal) 
will be compared with follow-up measurements and will be summarized using n, mean, 
SD, median, minimum, and maximum by joint and presented in a listing.  
Joint Contracture Severity Scale will be summarized using n and percent to summarize 
by severity category and presented in a listing. 
Wound Closure will be summarized using n and percent and presented in a listing. 
Modified Vancouver Scar Scale (mVSS) evaluated at 2, 3, 6 and 12 months after SSG 
will be summarized using number of observations (n) in each category by visit and 
presented in a listing. 
Severity of pruritus as assessed by the Numerical Response Scale (NRS) at SSG ‘take’ 
(7 - 10 days after application of SSG) and 1, 2, 3, 6, and 12 months post SSG will be 
summarized using n, mean, SD, median, minimum, and maximum by visit and presented 
in a listing. 
11.4  Final Analysis Plan 
Full details of the planned analyses will be addressed in the statistical analysis plan 
(SAP), including specified subset of outputs for the DSMB.  
In general, no inferential statistics are to be performed due to the small sample size and 
single arm study design unless specified otherwise in the statistical analysis plan. All 
statistical analyses will be based on treated population, which includes all subjects treated 
with BTM. No interim analysis is planned.  

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12 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. 
Source documents are where data are first recorded, and from which subjects’ 
CRF/eCRF data are obtained. These include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, or evaluation checklists, 
pharmacy records, diaries, microfiches, videos, radiographs, correspondence, recorded 
data from automated instruments, or other data collection events, copies or transcriptions 
certified after verification as being accurate and complete, photographs or digital photo 
files, x-rays, and subject files and records kept at the pharmacy, at the laboratories, and 
medico-technical departments involved in the clinical trial.  
The protocol does not permit entering data directly into electronic data capture. Case 
Report Form entries will NOT be considered source data [the site of the original recording 
of written or electronic record of trial data].  All documents will be stored securely in 
confidential conditions. On all trial-specific documents, other than the signed consent, the 
participant will be referred to by the subject's number/code, not by name. 
Each participating site will maintain appropriate medical and research records for 
compliance with ICH E6, and regulatory and institutional requirements for the protection 
of confidentiality of subjects.  Each site will permit authorized representatives of PolyNovo 
and regulatory agencies to examine (and when required by applicable law, to copy) 
research records for the purposes of quality assurance reviews, audits, and evaluation of 
the trial safety, progress and data validity.   

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13 QUALITY CONTROL AND QUALITY ASSURANCE 
Investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/Internal Ethics 
Committee review, and regulatory inspection(s) by providing direct access to source 
data/documents.  Each site should have standard operating procedures (SOPs) and/or a 
quality management plan that describe:   
• How data will be evaluated for compliance with the protocol and for accuracy in 
relation to source documents.  
• The documents to be reviewed (e.g. CRF/eCRFs, clinic notes, device 
accountability 
records, 
laboratory 
reports, 
specimen 
tracking 
logs, 
diaries/questionnaires, digital images, video recordings, surgery or procedure 
records), who is responsible, and the frequency for reviews.   
• Who will be responsible for addressing quality assurance issues (correcting 
procedures that are not in compliance with protocol) and quality control issues 
(correcting errors in data entry).  
• Staff training methods and how such training will be tracked. 
13.1 
Site Audits and Monitoring 
Ten percent of clinical investigational sites will be audited for compliance and quality 
standards. As detailed in Section 13.1, monitoring will be performed according to ICH 
GCP as clinical sites are qualified, initiated and closed for trial participation. Data will be 
evaluated for compliance with the protocol and accuracy in relation to source documents. 
Following written standard operating procedures, the monitors will verify that the clinical 
trial is conducted and data are generated, documented and reported in compliance with 
the protocol, GCP and the applicable regulatory requirements. Clinical trial sites are 
required to make trial source documents and records available for inspection by both 
auditors and monitors. 

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14 ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1 
Ethical Standard 
The Investigator will ensure that this trial is conducted in full conformity with the principles 
set forth by the United States (US) Food, Drug, and Cosmetic Act codified in 21 CFR and 
in the International Conference on Harmonization Good Clinical Practice guidelines (ICH 
GCP E6); the ethical requirements of the European Union Directive 2001/20/EC, and all 
applicable international standards, government regulations and Institutional research 
policies and procedures.  This clinical trial is to be conducted in accordance with the 
ethical principles that have their origins from the Declaration of Helsinki. 
14.2 
Institutional Review Board (IRB) 
Subjects in a clinical trial are afforded protection by the process of the clinical 
investigational plan being reviewed by the Institutional Review Board of each Institution 
at which the trial is to be conducted. This body of people (both medical/paramedical and 
lay) scrutinize the research protocol, ensuring that the protocol, subject information and 
the trial ICF promise a risk-minimized trial and protection of the subject’s rights and 
confidentiality. 
Each participating institution must provide for the review and approval of this protocol and 
the associated ICF, surgical consent (as applicable), HIPPA authorization (as applicable), 
and subject information sheets by an Office for Human Research Protections (OHRP) 
registered IRB. Any amendments to the protocol, ICF or subject information sheets must 
also be approved before they are utilized. In the United States, only institutions holding a 
current US Federal-wide Assurance issued by OHRP may participate. 
14.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate 
in the trial and continues throughout study participation.  Extensive discussion of risks 
and possible benefits of participation will be provided to subjects and their families, if 
applicable.  An ICF describing in detail the study procedures and risks will be given to the 
subject or his/her legal representative.  Consent forms will be IRB-approved, and the 
subject is required to read and review the document or have the document read to him or 
her.  The Investigator or designee will explain the research study to the subject and 
answer any questions that may arise.  The subject will sign the informed consent 
document prior to any study-related assessments or procedures.  Subjects will be given 

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the opportunity to discuss the trial with their family or legal representative or think about 
it prior to agreeing to participate.  They may withdraw consent at any time throughout the 
course of the study.  A copy of the signed informed consent document will be given to the 
subject or their legal representative for their records.  The rights and welfare of the 
subjects will be protected by emphasizing to them that the quality of their clinical care will 
not be adversely affected if they decline to participate in this trial. 
If non-English speakers will be enrolled, a translated ICF will be available and an 
appropriate person will conduct the consent process.  Each investigational site will be 
provided both types of ICF models.  Each institution may revise or add information to the 
ICF to comply with their consent processes, but may not remove procedural or risk 
content from the model ICF.  All changes to the ICF must be approved in writing by PPD 
prior to consenting of subjects. 
The consent process will be documented in the clinical research record.   
14.3.1 Consent in critical care 
If the subject is awake and oriented, they will be apprised of the extent and severity of 
their burn and the usual treatment plan at the institution. They will then be verbally 
informed about the trial objectives, followed by an in-depth discussion of what the BTM 
intervention means for the subject (e.g. potential risks).   
If the subject is unable to give Informed Consent for any reason, but the Investigator/Co-
Investigator feels that a better outcome will be gained from using BTM, open discussion 
may be held with subject’s legal representative. If, after the opportunity to digest the 
information and to ask questions, those parties agree with the Investigator/Co-
Investigator, consent can be signed by the subject’s legal representative.  
14.3.2 Vulnerable populations 
The nature of the burn injuries studied entails risk of burn-related morbidity and mortality, 
which increases as burn size as a percentage of TBSA increases. However, the majority 
of these injuries are sustained by young men in their mid-20s who are fit and well prior to 
their injury. No truly vulnerable population (i.e., children less than 18 years of age, 
pregnant women, and paraplegics) will be recruited into this traditional feasibility trial. 

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14.4 Subject Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, 
PolyNovo, and their agents. This confidentiality is extended to cover testing of biological 
samples, procedures and any trial information relating to participating subjects. The trial 
protocol, documentation, data, and all other information generated will be held in strict 
confidence. The subject will be identified only an ID number on the CRF, data listings, 
reports, summaries and in any paper/electronic format or database.  No information 
concerning the trial or the data will be released to any unauthorized third party without 
prior written approval of the PolyNovo. 
All documents will be stored securely and only accessible by trial staff and authorized 
personnel. Clinical information will not be released without written permission of the 
subject, except as necessary for monitoring by IRB, FDA, PolyNovo, applicable regulatory 
authority or PolyNovo’s designee. The trial will anonymize data as soon as it is practical 
to do so.  The trial protocol, documentation, data, and all other information generated will 
be held in strict confidence.  No information concerning the trial or the data will be 
released to any unauthorized third party without prior written approval of PolyNovo. 
PolyNovo and its authorized representatives may inspect all documents and records 
required to be maintained by the Investigator, including but not limited to, medical records 
(office, clinic, or hospital) for the subjects in this trial. The clinical trial site will permit 
access to such records. 
Photographic data will be de-identified. Since facial burns are not included in the protocol, 
there will be no reason to take facial images, which might identify subjects.  
14.5 Future Use of Stored Specimens 
Not applicable - there are no stored specimens in this trial.   

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15 
DATA HANDLING AND RECORD KEEPING 
The investigators are responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported in accordance with ICH E6.  All source documents should 
be completed in a neat, legible manner to ensure accurate interpretation of data.  The 
investigators will maintain adequate case histories of trial subjects, including accurate 
case report forms (CRF/eCRFs) and source documentation.  
15.1 Data Management Responsibilities 
Data collection and complete and accurate documentation are the responsibility of the 
trial staff under the supervision of the site Principal Investigator.  All source documents, 
photographs and laboratory reports must be reviewed by the trial team and data entry 
staff, which will ensure that they are accurate and complete. Unanticipated problems and 
adverse events must be reviewed by the Investigator or designee.   
The contract research organization (CRO), Pharmaceutical Products Development (PPD) 
will be responsible for data management, quality review, analysis, and reporting of the 
trial data. 
15.2 Data Capture Methods 
A centralized electronic data capture system will be utilized for this clinical trial. Electronic 
case report forms (eCRFs) will be utilized to capture all data and from which all source 
data are entered.  Investigational sites with defined users will be given access using a 
password for entry and specific permissions will be given depending on the delegation of 
responsibilities at the site. Sites are expected to enter data as it relates to the Schedule 
of Assessments and Procedures (Appendix 1) for each subject within 24 hours of the 
subject time point. 
15.3 Source Documents/Types of Data 
Data for this trial may include safety, laboratory, scar appearance and quality using 
photography, pruritus scale (NRS), mVSS, ROM joint contracture severity and outcome 
measures (e.g. microbiology and virology). 

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15.4 Schedule and Content of Reports 
The CRO will provide monthly reports on activities like: monitoring, enrollment, safety and 
data collection/cleaning, and reports for the data safety monitoring board as well as the 
final clinical study report.   
15.5 Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval of 
a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by local regulations. No 
records will be destroyed without the written consent of the PolyNovo, if applicable. It is 
the responsibility of the PolyNovo to inform the Investigator when these documents no 
longer need to be retained. 
15.6 Protocol Deviations 
A protocol deviation is any non-compliance with the clinical trial protocol, Good Clinical 
Practices, or Manual of Operations and other applicable requirements. The non-
compliance may be on the part of the subject, the Investigator, or trial staff. As a result of 
deviations, corrective actions are to be developed and implemented promptly. 
All deviations from the protocol must be addressed in the subject source documents and 
promptly reported to the PolyNovo or delegated CRO and the local IRB, according to their 
requirements.   

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16 PUBLICATION POLICY 
The results of the clinical investigation may be submitted for publication. 
PolyNovo requires Investigators to submit for consideration all manuscripts, case studies 
and presentation materials for PolyNovo review prior to submission to any peer-reviewed 
journal or meeting as per the Clinical Trial Agreement. The data will be formulated into 
the results section of a manuscript, maintaining full subject confidentiality. Photographic 
consent for publication is secured from each subject at enrollment. The manuscript will 
be submitted to a peer-reviewed journal. Additional manuscripts relating to video data 
may be submitted to a peer-reviewed online journal, e.g. ePlasty, or to the ‘online’ section 
of a ‘paper’ journal such as the Journal of Burn Care and Research. 
In order to publish in peer-reviewed journals, the trial MUST be registered with a Clinical 
Trial Registry. Additionally, PolyNovo requires Investigators to submit final peer-reviewed 
journal manuscripts that arise from PolyNovo research to the digital archive PubMed 
Central upon acceptance for publication. 
The International Committee of Medical Journal Editors (ICMJE) member journals have 
adopted a clinical trials registration policy as a condition for publication. The ICMJE 
defines a clinical trial as any research project that prospectively assigns human subjects 
to IP or concurrent comparison or control groups to study the cause-and-effect 
relationship between a medical IP and a health outcome.  Medical Investigational 
Products include drugs, surgical procedures, devices, behavioral treatments, process-of-
care changes, and the like. Health outcomes include any biomedical or health-related 
measures obtained in subjects or participants, including pharmacokinetic measures and 
adverse events. The ICMJE policy requires that all clinical trials be registered in a public 
trials registry such as ClinicalTrials.gov, which is managed by the National Library of 
Medicine. PolyNovo will register this clinical trial with www.clinicaltrials.gov. 

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17 LITERATURE REFERENCES 
References pertaining to ‘background’ information and non-clinical use of BTM  
1. Li A, Dearman B, Crompton K, et al. Evaluation of a novel biodegradable polymer for 
the generation of a dermal matrix. Journal of Burn Care and Research 2009;30(4):717-
728. 
2. Greenwood J, Li A, Dearman B, Moore T. Evaluation of NovoSorb™ novel 
biodegradable polymer for the generation of a dermal matrix. Part 1: In-vitro studies. 
Wound Practice and Research 2010;18(1):14-22. 
3. GreenwoodJ, Li A, Dearman B, Moore T. Evaluation of NovoSorb™ novel 
biodegradable polymer for the generation of a dermal matrix. Part 2: In-vivo studies. 
Wound Practice and Research 2010;18(1):24-34. 
4. Greenwood J, Dearman B. Split-skin graft application over an integrating, 
biodegradable temporising polymer matrix: Immediate and delayed. Journal of Burn 
Care and Research 2012;33(1):7-19. 
5. Greenwood J,  Dearman B. Comparison of a sealed, polymer foam biodegradable 
temporising matrix against Integra™ dermal regeneration template in a porcine wound 
model’ Journal of Burn Care and Research 2012;33(1):163-173. 
6. Dearman B, Stefani K, Li A, Greenwood J. ‘Take’ Of A Polymer-Based Autologous 
Cultured Composite Skin On An Integrated Temporizing Dermal Matrix: Proof Of 
Concep’ Journal of Burn Care and Research 2013;34(1):151-160. 
7. Dearman B, Li A, Greenwood J. Optimisation of a Polyurethane Dermal Matrix and 
Experience with a Polymer-based Cultured Composite Skin. Journal of Burn Care and 
Research 2014;35(5):437-448. 
References pertaining to previous clinical use of BTM  
8. Wagstaff M, Driver S, Coghlan P, Greenwood J. A randomised, controlled trial of 
Negative Pressure Wound Therapy via a biodegradable polyurethane foam in the 
management of decubitus ulceration. Wound Repair and Regeneration 2014;22:205-
211. 
9. Wagstaff M, Schmitt B, Coghlan P,  et al. A biodegradable polyurethane dermal 
matrix in reconstruction of free flap donor sites: A pilot study.’ ePlasty 2015;15:102-118. 

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10. Wagstaff M, Schmitt B, Caplash Y, Greenwood J. Free flap donor site 
reconstruction: A prospective case series using an optimized polyurethane temporizing 
matrix. ePlasty 2015;15:231-248. 
11. Greenwood J, Wagstaff M. The use of biodegradable polyurethane in the 
development of dermal scaffolds. in Cooper SL and Guan J (Eds) Advances in 
Polyurethane Biomaterials, Chapter 22, 2016. Woodhead Publishing Series in 
Biomaterials,  (Elsevier Inc.), Duxford, UK.  
12. Greenwood J. Hybrid biomaterials for skin tissue engineering. In Albanna M and 
Holmes J IV, ed. Skin Tissue Engineering and Regenerative Medicine 2016. Academic 
Press Elsevier Inc., London, UK. 
 
References pertinent to the justification for the study 
13. Heimbach D, Luterman A, Burke J, Cram A, et al. Artificial dermis for major burns. A 
multicentre randomized clinical trial. Ann Surg 1988;208(3):313-320.  
14. Heimbach D, Warden G, Luterman A, et al. Multicenter postapproval clinical trial of 
Integra Dermal Regeneration Template for burn treatment. J Burn Care Rehabil 
2003;24(1):42-48.  
 
References pertinent to the justification for effectiveness scales 
 
15. Brusselaers N, Pirayesh A, Hoeksema H, et al. Burn Scar Assessment: A 
systematic Review of Different Scar Scales. Journal of Surgical Research. 
2010;164:e115-e123. 
16. Fearmonti R, Bond J, Erdmann D. A review of Scar Scales and Scar Measuring 
Devices. Journal of Plastic Surgery. 2010;10:e43 
17. Phan N, Blome C, Fritz F, J Gerss l. Assessment of Pruritus Intensity: Prospective 
Study on Validity and Reliability of the Visual Analogue Scale, Numerical Rating Scale 
and Verbal Rating Scale in 471 Patients with Chronic Pruritis, Acta Dermato-
Venereologica. 2012;92:502-507. 
18. Schneider J, Holavanahalli R, Helm P, et al. Contractures in burn injury: defining the 
problem. Journal of burn care research. 2006;27(4):508-514. 

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19. Ständer S, Augustin M, Reich A, Blome C, et al. Pruritus assessment in clinical 
trials: consensus recommendations from the International Forum for the Study of Itch 
(IFSI) Special Interest Group Scoring Itch in Clinical Trials. Acta Dermato-
Venereologica. 2013;93(5):509-14. 
20. Fitzpatrick, TB. The validity and practicality of sun-reactive skin types I through VI. 
Archives of Dermatology 1988;124(6): 869-871. 
 

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18 APPENDICES 
 
 
 
 

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Appendix 1 - SCHEDULE OF ASSESSMENTS AND PROCEDURES 
 
Assessment/ 
Procedure 
Screening 
Baseline 
BTM ‘Take’ 
SSG 
SSG ‘Take’ 
Follow-up Visits 
Unscheduled/ 
Early 
Termination 
Visit 
Visit 1 
Visit 2 
Visit 3 Every  
3 – 5 days 
until SSG 
Visit 4  
~1 – 2 ma 
Visit 5 
7 - 10 days post 
SSG 
Visit 6/7  
~1 & 2 m 
post SSGb 
Visit 8/11/17 
~3, 6 & 12m 
post SSG 
Visit 9/10/12-16 
~4 - 11m post 
SSGc 
 
Day -7 to Day 
0 
Day 0 
~Day 3 – Day 
56 
Month 1 – 
Month 2 
Month 1 –  
Month 2 
Month 2 – 
Month 4 
Month 4 – 
Month 14 
Month 5 - 
Month14 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
Medical History & 
Demographics 
X 
 
 
 
 
 
 
 
 
Fitzpatrick Skin Typing 
Test 
Once between Screening and the 1 Month post SSG follow up (Visit 6) 
 
 
 
Inclusion/exclusion 
criteria assessment 
X 
X 
 
 
 
 
 
 
 
Physical exam & vital 
signs 
X 
X 
X 
X 
X 
X 
X 
 
X 
Assessment of 
Concomitant 
Medications/Therapies 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Β-hCG pregnancy test 
(urine) 
 
X 
 
 
 
 
X 
 
X 
Assessment of 
infection d 
X 
X 
X 
X 
X 
X 
X 
 
X 
Anesthesia, burn 
excision, hemostasis, 
BTM app 
 
X 
 
 
 
 
 
 
 
BTM ‘take’ rate 
 
 
 
X 
 
 
 
 
 

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Assessment/ 
Procedure 
Screening 
Baseline 
BTM ‘Take’ 
SSG 
SSG ‘Take’ 
Follow-up Visits 
Unscheduled/ 
Early 
Termination 
Visit 
Visit 1 
Visit 2 
Visit 3 Every  
3 – 5 days 
until SSG 
Visit 4  
~1 – 2 ma 
Visit 5 
7 - 10 days post 
SSG 
Visit 6/7  
~1 & 2 m 
post SSGb 
Visit 8/11/17 
~3, 6 & 12m 
post SSG 
Visit 9/10/12-16 
~4 - 11m post 
SSGc 
 
Day -7 to Day 
0 
Day 0 
~Day 3 – Day 
56 
Month 1 – 
Month 2 
Month 1 –  
Month 2 
Month 2 – 
Month 4 
Month 4 – 
Month 14 
Month 5 - 
Month14 
 
BTM integration 
assessment 
 
 
X 
 
 
 
 
 
 
Delamination and 
grafting 
 
 
 
X 
 
 
 
 
 
SSG ‘take’ 
 
 
 
 
X 
 
 
 
 
Joint Contracture 
Severity Scale and 
(ROM) 
 
X 
 
 
 
X 
X 
 
X 
Wound Closure 
 
 
 
 
 
X 
X 
 
X 
Pruritus Scale (NRS) 
 
 
 
 
X 
X 
X 
 
X 
Photographs 
 
X 
 
X 
X 
X 
X 
 
X 
mVSS 
 
 
 
 
 
X 
X 
 
X 
Assessment of AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physician’s survey 
 
 
 
X 
 
 
 
 
 
AE = adverse event; ~ = approximately; BTM = biodegradable temporizing matrix; FU = follow up; hCG = human chorionic gonadotropin; m = months; Numerical Rating 
Scale (NRS), (mVSS) modified Vancouver Scar Scale; ROM = range of motion; SSG = split-skin graft; wk = weeks 
The visit windows are intended as a guide to the investigators standard of care. 
a Note that in cases of multiple BTM implantations subjects will continued to be reviewed every 3-5 days until final SSG 
b Note that post SSG follow-up visits will occur once the final SSG has been applied 
c Follow-up performed via telephone (not in-person visits).  
d Assessment of infection includes clinical diagnosis supported by confirmatory laboratory findings. 

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Appendix 2: SCALES15-20 
All detailed procedures for each scale are included in the Site Manual of Operations. 
Pruritus: 
Numerical Rating Scale (NRS): 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
Itch 
 
 
 
 
 
 
 
 
 
Worst 
Imaginable 
Itch 
 
 
 

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Range of Motion (ROM): 
ROM measurement (measured with goniometer for each affected joint) 
Joint Contracture Severity Scale    
1=mild  
2=moderate  
3=severe 
 
 
 

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Modified Vancouver Scar Scale (mVSS): 
Measured for each lesion 
Pigmentation: 
0 – Normal color (resembles nearby skin) 
1 – Hypopigmentation 
2 – Hyperpigmentation 
3 – Combination/Mixed 
Vascularity: 
0 – Normal 
1 – Pink (slightly increased in local blood supply) 
2 – Red (significant increase in the local blood supply) 
3 – Purple (excessive local blood supply) 
Pliability 
0 – Normal 
1 – Supple (flexible with minimal resistance) 
2 – Yielding (giving way to pressure) 
3 – Firm (solid/inflexible, not easily moved, resistant to manual pressure) 
4 – Banding (rope-like, blanches with extension of scar, does not limit range of 
motion) 
5 – Contracture (permanent shortening of scar producing deformity or distortion, 
limits range of motion) 
Height (mm) of burn lesion 
0 – Normal (flat) 
1 - <2 
2 - >2 and <5 
3 - ≥5 
Total Score:   ______ 
 

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Surgeon’s Assessment of BTM Application: 
BTM is easy to use: 
1 – Strongly Agree 
2 – Agree 
3 – Neutral 
4 – Disagree 
5 – Strongly Disagree 
BTM is easy to apply: 
1 – Strongly Agree 
2 – Agree 
3 – Neutral 
4 – Disagree 
5 – Strongly Disagree 
BTM is easy to delaminate: 
1 – Strongly Agree 
2 – Agree 
3 – Neutral 
4 – Disagree 
5 – Strongly Disagree 
BTM is a product I would use for burn patients: 
1 – Strongly Agree 
2 – Agree 
3 – Neutral 
4 – Disagree 
5 – Strongly Disagree 
 
 

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Fitzpatrick Skin Typing Test: 
 

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