A Multicenter, Open-label, Study of StrataGraft® Skin Tissue in Adult Subjects With Deep Partial-Thickness Thermal Burns
Phase: PHASE3
Conditions: Deep Partial-thickness Burn
Sponsor: Stratatech, a Mallinckrodt Company

Official Title:     A Multicenter, Open-label, Study of StrataGraft Skin Tissue in Adult 
Subjects with Deep Partial-thickness Thermal Burns 
 
                  NCT Number:     NCT04123548 
 
          Document Date:     Protocol Amendment 1 (Version 2.0):  02 October 2020 

 
 
 
 
 
 
 
 
STRATAGRAFT® SKIN TISSUE 
 
 
 
A MULTICENTER, OPEN-LABEL, STUDY OF 
STRATAGRAFT® SKIN TISSUE IN ADULT SUBJECTS 
WITH DEEP PARTIAL THICKNESS THERMAL BURNS 
 
 
Protocol Number: MNK01053115 
Regulatory Agency Identifying Number (IND): 010,113  
 
 
 
Original Protocol, Version 1, dated 26 August 2019 
Amendment 1 (Version 2.0), dated 02 October 2020 
Short Title: StrataCAT 
Description: StrataGraft skin tissue is a living, bioengineered cellular tissue construct that is 
grown in a rectangular 100 square centimeter format. 
 
This document is a confidential communication of Stratatech, a Mallinckrodt Company. 
Acceptance of this document constitutes the agreement by the recipient that no unpublished 
information contained herein will be published or disclosed without the prior written approval of 
Mallinckrodt, except that this document may be disclosed to appropriate institutional review 
boards/ethical committees so long as they are requested to maintain its confidentiality. 
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2  
 
 
 
SPONSOR SIGNATURE PAGE 
 
My signature, in conjunction with the signature of the investigator, confirms the agreement of 
both parties that the clinical study will be conducted in accordance with the protocol and 
applicable guidance documents and regulations including, but not limited to: 
• International Council for Harmonisation (ICH) E6(R2): Integrated Addendum to ICH 
E6(R1): Guideline for Good Clinical Practice, which has its ethical foundation in the 
Declaration of Helsinki  
• the US Code of Federal Regulations (CFR) (as appropriate, including 42 CFR 11: Final 
Rule for Clinical Trials Registration and Results Information Submission)  
• NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information 
• all applicable national and local regulations (as appropriate, including the European 
Clinical Trials Regulation)  
• protections for privacy (as appropriate, including the European General Data Protection 
Regulation  
• provisions of all local ethics committees  
 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care. 
 
Refer to e-signature page 
Sponsor Signature 
 MD, MPh, MBA 
 
 
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ACKNOWLEDGEMENT OF RECEIPT AND UNDERSTANDING OF 
SPONSOR STUDY MATERIALS 
 
 
My signature confirms that the clinical study will be conducted in accordance with the protocol 
and applicable laws and other regulations including, but not limited to, the International Council 
for Harmonisation (ICH) Guideline for Good Clinical Practice (GCP), the US CFR, protections 
for privacy, and generally accepted ethical principles such as the Declaration of Helsinki. 
 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care. 
 
I confirm that I have received, read, and understood the following document(s) for: 
 
PRODUCT:  
StrataGraft® skin tissue 
 
STUDY: 
Protocol MNK01053115 
Protocol Version 2 Amendment 1 
 
PRINCIPAL/COORDINATING INVESTIGATOR(S) 
 
Name: 
Title: 
 
 
SIGNATURE_________________________________________DATE: _______________ 
 
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1. 
SYNOPSIS 
Name of Sponsor/Company: 
Stratatech, a Mallinckrodt Company 
Name of Investigational Product: 
StrataGraft® skin tissue 
Name of Active Ingredient: 
Viable and metabolically active allogeneic human (near-diploid human keratinocytes [NIKS]) and 
human dermal fibroblasts 
Protocol Number: MNK01053115 
Phase: 3b 
Country: USA 
Title of Study:  
A Multicenter, Open-label, Study of StrataGraft® Skin Tissue in Adult Subjects with Deep 
Partial-Thickness Thermal Burns 
Study Center(s): Multicenter 
Study Period: 24 Weeks 
Estimated date first subject enrolled: November 2019 
Estimated date last subject completed: 24 weeks afte  the 
date of the occurrence of either commercial availability of 
the product or Sponsor closure of the study, whichever 
comes first. 
Phase of development: 3b 
Study Objective(s)/Endpoint(s)/Outcome Measures(s) 
 
Primary Objective(s)/Endpoint(s)  
Primary Objective 
Primary Endpoint 
Demonstrate the safety of a single appli ation 
of StrataGraft skin tissue in the post-excision 
treatment of deep partial-thickness (DPT) 
thermal burns that contain intact dermal 
elements. 
Count and percent of subjects with treatment-
emergent adverse events (TEAEs)  
 
Primary Outcome Measure:  
Title: 
Number of participants with TEAEs during the study  
 
Description: 
Total count of participants with TEAEs during the study 
 
Timeframe:  
Approximately 24 weeks  
 
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Other Pre-specified Objective(s)/Endpoint(s):  
Other Objective(s) 
Other Endpoint(s) 
Demonstrate the clinical outcomes of a 
single application of StrataGraft skin tissue 
in the post excision treatment of thermally 
induced DPT burns that contain intact 
dermal elements. 
• Proportion of subjects with confirmed 
wound closure without autograft 
placement (ie, complete re-
epithelialization without drainage and 
subsequently verified with confirmation 
assessment) on or before Week 12 and 
supported by photo-documentation 
• 
Proportion of subjects with confirmed 
wound closure without autograft 
(verified with confirmation assessment) 
at each visit and supported by photo-
documentation 
• 
Proportion of subjects without 
autografting who maintain durable 
wound closure by Week 24 
• 
Time to confirmed wound closure 
without autografting (verified with 
confirmation assessment) 
• 
Treatment site skin quality data: The 
total observed POSAS by clinician and 
by subject. Per site descriptive statistics 
will be presented separately for 
clinician and subject values for each of 
the individual POSAS items and the 
total POSAS score, represented as the 
mean score across all treatment sites 
and supported by photo-documentation. 
• 
Number (%) of subjects with wound 
infection-related events 
 
 
Exploratory Objective(s)/Endpoint(s):  
Exploratory Objective 
Exploratory Endpoint 
Assess for healthcare resource utilization 
(HCRU) throughout the study period 
• 
Location of care for StrataGraft application (eg, 
inpatient hospital, outpatient/ambulatory 
hospital, clinic, etc.) 
• 
Treatments used for all other burn areas 
following excision and % total body surface 
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area (TBSA) treated with each (other than 
StrataGraft treatment sites) 
• 
Number of Operating Room (OR) procedures 
required for burn treatment: excisions, 
application of StrataGraft tissue and all other 
grafting procedures, including autografts, 
allografts, and xenografts  
• 
Duration of each OR procedure  
• 
Length of hospital stay  
• 
Prescription drugs given at discharge from the 
hospital for wound-related events including 
pain control, itch, psychotropics, and 
antibiotic   
• 
Re-admission within 30 days after discharge 
• 
Whether a re-admission is planned 
• 
Length of hospital stay of re-admission 
Study Design: This is a prospective, open-label, single-arm study assessing the safety and clinical 
outcomes of StrataGraft skin tissue in the treatment of DPT thermal burn injuries with intact dermal 
elements. Study enrollment will be approximately 100 subjects but will continue until StrataGraft 
becomes commercially available or until th  Sp nsor decides to close the study. Enrollment will 
include subjects with a minimum of 3% and up to 50% TBSA of partial +/- full thickness thermal 
burn. Treatment will include a single pplic tion of up to 1:1 meshed StrataGraft skin tissue on DPT 
wound(s) totaling no more than approximately 2000 square centimeters in area (no more than 3 study 
treatment thermal burn areas and no more than 20 StrataGraft tissues applied to the study treatment 
areas). The wound bed must be cle n, excised and have bleeding controlled prior to StrataGraft tissue 
application. The tissues may be anchored with tissue adhesive, staples, or sutures, covered with a 
nonadherent, nonocclusive contact layer and additional secondary dressings per institutional standard 
of care (dressings should not contain silver). Safety assessments will include monitoring of TEAEs, 
serious adverse events (SAEs), wound infections, and clinically significant vital signs, laboratory test 
results, and immunological changes. Wound assessments will include measurements for average 
depth, length, and width for calculations of area and percent epithelialization. Wound assessments 
will be facilitated by photographs taken by the subject and/or taken by the clinical study site staff at 
study visits throughout the study. Scar evaluation using the POSAS will be conducted. Additionally, 
HCRU data will be collected. All subjects eligible to be consented throughout the duration of the 
study following application of StrataGraft skin tissue to be part of a contact database and follow-up 
registry; subjects will have the choice to decline with no impact to their participation in the study. In 
addition, a subset of 10 subjects (sourced from across all the sites) with closed wounds will be 
separately consented to have a punch biopsy (measuring 3 mm) taken from the center of the healed 
burn wound, and another punch biopsy measuring 3 mm taken from non-burned healthy skin. A 
histological evaluation of both samples will be done to analyze and contrast the skin architecture in 
the healed burn wound with healthy skin. The biopsy will happen at the study visit Week 12, 
regardless of when wound closure occurs. 
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Methodology: The data generally will be summarized with descriptive statistics. The Kaplan-Meier 
estimate will be performed to determine time to confirmed wound closure. 
Sample Size Justification: No sample size determinations were performed for this study. 
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Number of subjects (planned): approximately 100 
Diagnosis: Thermally induced DPT burns that contain intact dermal elements and for which surgical 
excision and autograft are clinically indicated 
Inclusion Criteria: 
Subject-specific criteria: 
1. Men and women ≥ 18 years  
2. Written informed consent 
3. Sufficient healthy skin identified and designated as a donor site in the event that the 
StrataGraft treatment site requires autografting 
4. 3% up to <50% TBSA of partial +/- full thickness th rmal burns 
Treatment site-specific criteria: 
5. Thermal burn(s) with intact dermal elements for which excision and autografting are 
clinically indicated 
6. Total treatment areas no more than approximately 2000 cm2 and total tissues no more than 
20 tissues. Total burn may consist of up to 3 noncontiguous burn sites 
7. First excision and grafting of study treatment sites  
8. Thermal burn(s) on the torso, upper extremities, and lower extremities 
Exclusion Criteria: 
Subject-specific criteria: 
1. Pregnant women 
2. Prisoners 
3. Subjects receiving systemic immunosuppressive therapy at the time of injury 
4. Subjects with a known history of malignancy 
5. Pre-admission insulin-dependent diabetic subjects 
6. Subjects with concurrent conditions that, in the opinion of the investigator, may compromise 
subject safety or study objectives 
7. Expected survival of less than 3 months 
8. Participation in a study of an investigational device, pharmaceutical, or biologic drug within 
90 days prior to enrollment 
(Participants in nutritional or non-interventional observational studies where no 
investigational product or device is given or administered will not be excluded.) 
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Treatment site-specific criteria: 
9. Full-thickness burns 
10. Chronic wounds  
11. The face, head, neck, hands, feet, digits, buttocks, perineum/genitals, and areas over joints 
12. Treatment sites immediately adjacent to unexcised eschar 
13. Clinical or laboratory determination of infection at the anticipated treatment sites at time of 
StrataGraft placement 
Investigational Product, Dosage and Mode of Administration:  
StrataGraft skin tissue is applied once to no more than 3 noncontiguous burn sites, totaling a 
maximum study treatment area of no more than approximately 2000 cm2, and using no more than 
20 tissues. 
Duration of Treatment:  
Subject evaluated for 24 weeks after the StrataGraft skin tissue placement 
Reference Therapy, Dosage and Mode of Administration:  
None 
Statistical Methods:  
For all safety assessments, the data will be summarized with descriptive statistics. 
For all other outcomes, the data will be summarized with descriptive statistics and some of these with 
95% confidence intervals. The Kaplan-Meier estimate will be computed to determine the median time 
to confirmed wound closure without autog ft placement (verified with confirmation assessment). No 
hypothesis testing will be conducted. 
 
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SUMMARY OF CHANGES FOR AMENDMENTS 
Amendment 1 was primarily initiated due to the need for provisions for publicly stated 
emergencies. Additionally, DSMB safety monitoring has been replaced with monitoring by a 
Sponsor Safety Committee, safety laboratory assessments added, and clarification added for 
wound assessments, for collection of photographs, for collection of data for prescription 
medications plus other minor changes and administrative changes. Appendix 1 provides all 
changes in detail. 
 
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2. 
TABLE OF CONTENTS AND LIST OF TABLES 
TABLE OF CONTENTS 
 
TITLE PAGE ...................................................................................................................................1 
SPONSOR SIGNATURE PAGE ....................................................................................................2 
ACKNOWLEDGEMENT OF RECEIPT AND UNDERSTANDING OF SPONSOR 
STUDY MATERIALS .................................................................................................3 
1. 
SYNOPSIS ...................................................................................................................4 
SUMMARY OF CHANGES FOR AMENDMENTS ...................................................................10 
2. 
TABLE OF CONTENTS AND LIST OF TABLES ..................................................11 
3. 
ABBREVIATIONS AND DEFINITIONS OF TERMS ............................................16 
4. 
INTRODUCTION ............................................. ... .................................................17 
4.1. 
Study Rationale .......................................... ...... .......................................................17 
4.2. 
Assessment of Potential Risks and Benefits ...............................................................18 
4.3. 
Summary of Relevant Clinical Studies ......................................................................18 
5. 
STUDY OBJECTIVES AND PURPOSE ..................................................................20 
5.1. 
Primary Objective ......................
.............................................................................20 
5.2. 
Other Objective(s) ..........
....... ................................................................................20 
5.3. 
Exploratory Objectives .... .....
..............................................................................21 
5.4. 
Subgroup Analyses .......
..........................................................................................21 
6. 
INVESTIGATIONAL PLAN .....................................................................................22 
6.1. 
Overall Study Design ..................................................................................................22 
6.1.1. 
Schedule of Assessments ............................................................................................24 
6.1.2. 
Study Design Rationale ..............................................................................................26 
6.1.3. 
Treatment Rationale ....................................................................................................26 
6.1.4. 
End of Study Definition ..............................................................................................26 
6.2. 
Number of Subjects ....................................................................................................26 
6.3. 
Treatment Assignment ................................................................................................26 
6.4. 
Dose Adjustment Criteria ...........................................................................................26 
6.5. 
Provisions for Remote Assessment Methods .............................................................27 
6.6. 
Criteria for Study Stopping .........................................................................................27 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................28 
7.1. 
Subject Inclusion Criteria ...........................................................................................28 
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7.2. 
Subject Exclusion Criteria ..........................................................................................28 
7.3. 
Subject Withdrawal Criteria .......................................................................................29 
8. 
TREATMENT OF SUBJECTS ..................................................................................30 
8.1. 
Description of Study Treatment ..................................................................................30 
8.2. 
Concomitant Medications ...........................................................................................30 
8.3. 
Concomitant Procedures .............................................................................................31 
8.4. 
Randomization and Blinding ......................................................................................31 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................32 
9.1. 
Study Treatment ..........................................................................................................32 
9.2. 
Study Treatment Packaging and Labeling ..................................................................32 
9.3. 
Study Treatment Storage .................................. ... ...................................................32 
9.4. 
Study Treatment Preparation .............................
. .................................................32 
9.5. 
Study Administration .............................. .. ....... .......................................................32 
9.6. 
Study Treatment Handling and Disposal ... ................................................................33 
10. 
ASSESSMENT OF OTHER PRE-SPECIFIED ENDPOINTS ..................................34 
10.1. 
Other Endpoints ....................... ..
... ......................................................................34 
10.2. 
Exploratory Endpoints ........ ..... . ...........................................................................35 
10.3. 
Subgroup Analyses .........
...... ................................................................................35 
11. 
OTHER ASSESSMENTS ...... ...............................................................................36 
12. 
SAFETY ASSESSMENT ..........................................................................................37 
12.1. 
Primary Safety Endpoint .............................................................................................37 
12.2. 
Safety Parameters Specific to Therapeutic Category .................................................37 
12.2.1. 
Incidence of infection .................................................................................................37 
12.2.2. 
Archival plasma and leukocyte samples .....................................................................38 
12.2.3. 
Immunology ................................................................................................................38 
12.2.4. 
Regrafting and Delayed Wound Healing ....................................................................38 
12.3. 
Standard Safety Parameters ........................................................................................38 
12.3.1. 
Demographic/Social/Medical History ........................................................................38 
12.3.2. 
Vital Signs ..................................................................................................................38 
12.3.3. 
Weight and Height ......................................................................................................38 
12.3.4. 
Physical Examination .................................................................................................38 
12.3.5. 
Laboratory Assessments .............................................................................................38 
12.3.5.1. 
Hematology .................................................................................................................39 
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12.3.5.2. 
Blood Chemistry .........................................................................................................39 
12.3.5.3. 
Immunology Assessments ..........................................................................................39 
12.3.5.4. 
Pregnancy Testing ......................................................................................................39 
12.4. 
Adverse Events and Serious Adverse Events .............................................................39 
12.5. 
Intensity of Adverse Event .........................................................................................40 
12.6. 
Relationship to Study Drug ........................................................................................40 
12.7. 
Other Adverse Event ...................................................................................................40 
12.8. 
Pregnancy Events ........................................................................................................40 
12.9. 
Recording Adverse Events .........................................................................................41 
12.10. 
Reporting Adverse Events ..........................................................................................41 
13. 
STATISTICS .................................................... ... ...................................................42 
13.1. 
Sample Size Determinations ..............................
. .................................................42 
13.2. 
Analysis Populations .............................. .. ....... .......................................................42 
13.3. 
Statistical Analysis .............................
.... ................................................................42 
13.3.1. 
Primary Safety Endpoint Analysis ...
......................................................................42 
13.3.2. 
Other Pre-specified Endpoint Analyses ......................................................................42 
13.3.3. 
Exploratory Efficacy Endpoints . . ...........................................................................43 
13.3.4. 
Subgroup Analyses .........
...... ................................................................................44 
13.3.5. 
Multiple Comparison Testing Methods ......................................................................44 
13.3.6. 
Interim Analyses ............ ..........................................................................................44 
13.3.7. 
Safety Analysis .. ...... ...............................................................................................44 
13.3.8. 
Handling of Missing Data ...........................................................................................45 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................46 
14.1. 
Study Monitoring ........................................................................................................46 
14.2. 
Audits and Inspections ................................................................................................46 
14.3. 
Monitoring Boards ......................................................................................................47 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................48 
16. 
ETHICS ......................................................................................................................49 
16.1. 
Ethics Review .............................................................................................................49 
16.2. 
Ethical Conduct of the Study ......................................................................................49 
16.3. 
Written Informed Consent ..........................................................................................49 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................50 
17.1. 
Inspection of Records .................................................................................................50 
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17.2. 
Retention of Records ..................................................................................................50 
18. 
LIST OF REFERENCES ............................................................................................51 
APPENDIX 1 PROTOCOL AMENDMENT HISTORY ...........................................................52 
 
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LIST OF TABLES 
Table 1: 
Abbreviations and Special Terms ...............................................................................16 
Table 2: 
Schedule of Assessments ............................................................................................24 
Table 3: 
Investigational Product ...............................................................................................30 
 
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3. 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
The following abbreviations and special terms are referenced by this study protocol as presented 
in Table 1. 
Table 1: 
Abbreviations and Special Terms  
Abbreviation or 
Special Term 
Explanation 
AE 
Adverse event 
allograft 
A transplant from 1 person to another person 
autograft 
Transplant of skin tissue from 1 location to another on same person 
CFR 
Code of Federal Regulations 
DPT 
Deep partial-thickness (has intact dermal elements) 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HCRU 
Health care resource u ilization 
HLA 
Human leukocyte a tigen 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethic  Committee 
IRB 
Institutional revi w board 
mITT 
Modified intention-to-treat 
NIKS 
Near-diploid human keratinocytes 
OR 
Operating Room 
POSAS 
Patient and observer scar assessment scale 
PRA 
Panel reactive antibodies 
SAE 
Serious adverse event 
SoC 
Standard of Care 
TBSA 
Total body surface area 
TEAE 
Treatment-emergent adverse event 
xenograft 
The transplant of an organ, tissue, or cells to an individual of another species. 
 
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4. 
INTRODUCTION 
Every year in the United States, approximately 45,000 patients experience burns that require 
them to be hospitalized, and of those individuals approximately 10 to 20% require surgical 
intervention such as autografting (American Burn, 2016). Depending upon the severity of the 
injury, hospitalization can often be protracted. Based on data in the 2017 National Burn 
Repository Annual Report, which includes data collected from 101 US burn centers in 37 states 
and the District of Columbia between 2008 and 2017, representing a cross-section of US 
hospitals, the average length of stay for survivors was slightly greater than 1 day per %TBSA 
burned (American Burn Association, 2017).  
After stabilization of the critical care issues in those who sustain a burn-injury, attention is 
directed toward burn wound management. The ultimate aim of burn wound management is to 
prevent wound infection and facilitate closure of the wounds, either spontaneously or by 
autologous skin grafts. Key elements of burn wound management include cleansing, 
debridement and/or surgical excision, and application topical antimicrobial agents and dressings.  
Regardless of the age of the patient, evidence suggests that early excision of burn eschar is 
effective in decreasing morbidity, improving the mortality rate and reducing length of stay 
(Muller, 1994; Herndon, 1989), as well as hospital costs (Munster, 1994). Excised areas are 
usually closed with autograft, or if not available, allograft, xenograft or other skin substitute is 
used until autograft is available or the wound spontaneously closes. Availability of autologous 
donor tissue, however, is limited by the extent of the burn injury, and in larger injuries, donor 
sites are often repeatedly harvested, increasing the likelihood of chronic scarring at those sites. 
As such, methods to reduce the amount of d nor tissue needed to achieve wound closure are 
always sought.  
4.1. 
Study Rationale 
StrataGraft skin tissue is an allogeneic tissue-engineered product. StrataGraft skin tissue is under 
development by Stratatech Corpo tion, the Sponsor Company, as an alternative to autografting 
in the closure of thermal burns containing intact dermal elements. 
Clinical data from adults suggest that treatment of DPT thermal burns with StrataGraft tissue can 
result in wound closure while reducing or eliminating the need for autograft. Clinical data have 
also shown that this tissue construct does not transplant but is replaced by the subject’s cells as 
the wound heals (Sponsor unpublished data). 
This study is being conducted in order to provide continued access to StrataGraft skin tissue for 
clinical sites following the closure of enrollment to the STRATA2016 study. This study will 
collect safety and clinical outcomes in a population of subjects with thermally induced DPT 
burns that contain intact dermal elements. 
This study will be conducted in compliance with applicable regulations and guidance related to 
GCP and in compliance with this protocol. 
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4.2. 
Assessment of Potential Risks and Benefits 
Results to date indicate that StrataGraft skin tissue is well tolerated, and no acute clinical signs or 
symptoms of an allogeneic immune response have been reported. The most common noted 
adverse reaction associated with StrataGraft is pruritus.  
Subjects in this study will undergo surgical excision of the burn area. The risks associated with 
the surgical procedure include pain and bleeding at the surgical site as well as potential 
complications of anesthesia, such as nausea/vomiting, chills, and sore throat. A subset of 
10 subjects who achieve complete wound closure and have consented to study treatment will also 
undergo a biopsy of their healed StrataGraft-treated wound sites at Week 12 to histologically 
assess tissue architecture and any other histological tests as required. The risks associated with 
the procedure include those associated with application of a local anesthetic as well as pain or 
discomfort, bleeding, infection, and scarring at the biopsy site. All procedures and activities in 
this study, other than the actual application of StrataGraft tissue and skin biopsy, are generally 
accepted as standard of care (SoC) for subjects with thermal burns and do not present any 
increased risk to the subjects. 
StrataGraft skin tissue is a viable, bilayer, allogeneic human skin substitute composed of a fully 
stratified epithelial layer comprised of NIKS keratinocytes from a single human donor grown on 
a dermal equivalent comprised of purified Type I animal collagen containing normal human 
fibroblasts from a second donor. During development of the NIKS keratinocytes, these cells 
were previously exposed to murine feeder cells. These feeder cells were derived from a single 
source, thoroughly tested, and found to be free f detectable adventitious agents. 
 
 To comply 
with current Food and Drug Administration (FDA) xenotransplantation guidelines, 
 
 (FDA, 2016; 
Bloom, 2000) archival blood samples will be collected at baseline and retained in accordance 
with FDA guidelines.  
The benefit of treating burns wi h StrataGraft skin tissue is that the viable cells of StrataGraft 
tissue produce and secrete a variety of growth factors, cytokines, and antimicrobial peptides that 
are collectively anticipated to facilitate wound repair and tissue regeneration. 
More detailed information about the known and expected benefits, risks, and reasonably 
expected adverse events (AE) can be found in the Investigator’s Brochure. 
4.3. 
Summary of Relevant Clinical Studies 
Previous studies in adults with DPT thermal burns have demonstrated that StrataGraft skin tissue 
is generally safe with salutary clinical outcomes in regard to closure of DPT burns and 
elimination of autograft placement in the majority of subjects.  
The Phase 1b study, “Open-label, Controlled, Randomized, Multicenter, Dose Escalation Study 
Evaluating the Safety and Efficacy of StrataGraft® Skin Tissue in Promoting the Healing of the 
Deep Partial-Thickness Component of Complex Skin Defects as an Alternative to Autografting,” 
(STRATA2011) was an open-label, dose-escalation, multicenter study evaluating the safety, 
tolerability, and efficacy of StrataGraft skin tissue in promoting the healing of complex skin 
defects containing intact dermal elements. In this study, StrataGraft skin tissue was applied once 
to DPT burns to assess autologous tissue regeneration with reduction or elimination of 
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autografts. This study included subjects with thermal burns of 3 to 49% TBSA. Each subject had 
2 comparable burn wound areas identified, excised to remove nonviable tissue, and randomized 
to receive StrataGraft skin tissue or autograft. Thirty subjects were enrolled with 10 subjects in 
Cohort 1 receiving up to 220 cm2 of refrigerated StrataGraft skin tissue and 10 subjects in Cohort 
2 receiving up to 440 cm2 of refrigerated StrataGraft skin tissue. Ten subjects in Cohort 3 
received up to 440 cm2 of thawed cryopreserved StrataGraft skin tissue. None of the subjects 
treated with StrataGraft skin tissue exhibited any significant safety concerns and none underwent 
autografting prior to Day 28. Additionally, 27 of the 28 per-protocol subjects (96%) exhibited 
complete wound closure of StrataGraft treatment sites at Month 3. Molecular analysis of biopsies 
taken from treated wound sites at Month 3 demonstrated no evidence of StrataGraft skin tissue 
DNA, indicating that the cellular components of StrataGraft skin tissue were no longer present. 
The Phase 3 study “A Multicenter, Open-Label, Randomized Comparison of the Efficacy and 
Safety of StrataGraft Skin Tissue vs Autograft in Adult Subjects with Thermal Burns” 
(STRATA2016) is an open-label, controlled, randomized, multicenter study evaluating the 
efficacy and safety of StrataGraft skin tissue in the treatment of complex skin defects due to 
thermal burns that contain intact dermal elements and for which surgical excision and 
autografting are clinically indicated. The number of enrolled subjects was 71 and the last subject 
completed all study procedures in March 2020. No Stra aGraft-related SAEs were reported. 
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5. 
STUDY OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
The primary objective of this study is to assess the safety of a single application of StrataGraft 
skin tissue in the treatment of adults with thermally induced DPT burns that contain intact 
dermal elements. 
Primary Objective(s)/Endpoint(s)/Outcome(s)  
Primary Objective 
Primary Endpoint 
Demonstrate the safety of a single 
application of StrataGraft skin tissue in 
the post excision treatment of thermally 
induced DPT burns that contain intact 
dermal elements. 
Count and percentage of subjects with TEAEs  
 
5.2. 
Other Objective(s) 
Other pre-specified endpoints will be assessed throughout the study period. 
 
Other Pre-specified Objective(s)/Endpoint(s)  
Other Objective 
Other Endpoints 
Demonstrate the clinical outcomes of a 
single application of StrataGraft skin 
tissue in the post excision treatment of 
thermally induced DPT burns that 
contain intact dermal elements. 
• 
Proportion of subjects with confirmed wound 
closure without autograft placement (ie, 
complete re-epithelialization without drainage 
and subsequently verified with confirmation 
assessment) on or before Week 12 and 
supported by photo-documentation 
• 
Proportion of subjects with confirmed wound 
closure without autograft (verified with 
confirmation assessment) at each visit and 
supported by photo-documentation 
• 
Proportion of subjects without autografting who 
maintain durable wound closure by Week 24 
• 
Time to confirmed wound closure without 
autografting (verified with confirmation 
assessment) 
• 
Treatment site skin quality data: The total 
observed POSAS by clinician and by subject. 
Per site descriptive statistics will be presented 
separately for clinician and subject values for 
each of the individual POSAS items and the 
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total POSAS score, represented as the mean 
score across all treatment sites and supported by 
photo-documentation 
• 
Number (%) of subjects with wound infection-
related events 
 
5.3. 
Exploratory Objectives 
Information for HCRU will be assessed throughout the study period. 
 
Exploratory Objective(s)/Endpoint(s)/Outcome(s)  
Exploratory Objective 
Exploratory Endpoint 
HCRU assessments 
• 
Location of care for StrataGraft application (eg, 
inpatient hospital, outpatient/ambulatory hospital, 
clinic, etc.) 
• 
Treatments used for all other burn areas following 
xcision and % TBSA treated with each (other than 
StrataGraft treatment sites) 
• 
Number of Operating Room (OR) procedures 
required for burn treatment: excisions, application of 
StrataGraft tissue and all other grafting procedures, 
including autografts, allografts, and xenografts  
• 
Duration of each OR procedure  
• 
Length of hospital stay  
• 
Prescription drugs given at discharge from the 
hospital for wound-related events including pain 
control, itch, psychotropics, and antibiotics 
• 
Re-admission within 30 days after discharge 
• 
Whether a re-admission is planned 
• 
Length of hospital stay of re-admission 
 
5.4. 
Subgroup Analyses 
Subgroup analyses include race (white, non-white), ethnicity, age (<65, ≥ 65), sex (male, 
female), size of area treated with StrataGraft (≤ 500 cm2, > 500 cm2), and overall TBSA of 
wound burden defined as burns TBSA plus donor site area (< median, ≥ median). 
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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a Phase 3b, open-label, multicenter study of adults evaluating the safety and clinical 
outcomes of StrataGraft® skin tissue in the treatment of thermally induced DPT burns that 
contain intact dermal elements. 
No randomization will be conducted for the study, as this study is designed to be a single arm 
study. 
Subjects may be assessed to have no more than 3 noncontiguous burn areas treated and receive 
no more than 20 tissues of StrataGraft skin tissue (for a total StrataGraft skin tissue treated area 
of no more than approximately 2000 cm2).  
The primary endpoint is count and percent of subjects with TEAEs. 
Other endpoints include:  
• The proportion of StrataGraft skin tissue-treated wound area with confirmed wound 
closure without autograft placement (ie, complete re-epithelialization without 
drainage and subsequently verified by confirmation assessment) on or before 
Week 12 and supported by photo-documentation. 
• The proportion of subjects with confirmed wound closure without autograft 
placement (verified with confirmation assessment) at each visit and supported by photo-
documentation. 
• The proportion of subjects without autografting achieving and maintaining durable 
wound closure by Week 24. Durable wound closure is achieved when a wound is 
observed as remaining closed at l ast 3 months after complete wound closure.  
• The time to confirmed wound closure without autograft placement (verified with 
confirmation assessment). For in-person visits, the investigator will assess the wound 
in person or alternatively assess a photo provided by the subject if the subject misses 
a visit. For the weeks in-between onsite visits, the subject will have a photo taken and 
send them to a photo repository beginning at discharge then weekly until Week 12 
and then every other week until Week 24. These photos will also be assessed by the 
principal investigator. 
• Skin quality and cosmesis assessments at Week 12 and Week 24 by the subject and 
observer using POSAS scores; these assessments will be supported both by 
photo-documentation and POSAS scores. 
• Number (%) of subjects with wound-infection related events. 
 
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The exploratory endpoints include collection of information for HCRU: 
• Location of care for StrataGraft application (eg, inpatient hospital, 
outpatient/ambulatory hospital, clinic, etc.) 
• Treatments used for all other burn areas following excision and %TBSA treated with 
each (other than StrataGraft treatment sites) 
• Number of OR procedures required for burn treatment: excisions, application of 
StrataGraft tissue and all other grafting procedures, including autografts, allografts, 
and xenografts  
• Duration of each OR procedure  
• Length of hospital stay  
• Prescription drugs given at discharge from the hospital for wound-related events 
including pain control, itch, psychotropics, and antibiotics 
• Re-admission within 30 days after discharge 
• Whether a re-admission is planned 
• Length of hospital stay of re-admission 
 
 
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6.1.2. 
Study Design Rationale 
This Phase 3b, open-label study provides the opportunity of continuing access of StrataGraft skin 
tissue at clinical study sites that participated in the prior Phase 3 study. Safety assessments and 
clinical outcomes will be collected and analyzed to supplement the safety information regarding 
this product, allow for collection of health economic data, and provide additional efficacy 
outcomes data. 
6.1.3. 
Treatment Rationale 
Observations in prior clinical studies suggest that StrataGraft skin tissue may promote healing of 
DPT burns with intact dermal elements. In prior studies with StrataGraft skin tissue in this 
population, no clinically important untoward effects have been associated solely with treatment 
with StrataGraft skin tissue. 
6.1.4. 
End of Study Definition 
Study end for a given subject will be marked following the r trieval of all Week 24 treatment 
assessments collected for the subject in the study and resolution of any complications from 
serious TEAEs. The study enrollment will not end until either the time that StrataGraft skin 
tissue is commercially available or the time that the Sponsor terminates the study, whichever 
occurs first. All subjects will be followed until th y complete their participation as described by 
this protocol. 
6.2. 
Number of Subjects 
Approximately 100 subjects will be scr ened and treated with StrataGraft skin tissue (enrolled 
into the study) until StrataGraft skin tissue is commercially available or until the Sponsor closes 
the study. 
6.3. 
Treatment Assignment 
Subjects who meet all inclusion criteria will receive StrataGraft skin tissue treatment. Subjects 
are considered enrolled into the study once they have StrataGraft skin tissue treatment applied to 
a burn site. Subjects will receive 1 application of StrataGraft skin tissue(s) to no more than 3 
burn sites with no more than 20 StrataGraft skin tissues applied to the burn sites and a total study 
treatment area of no more than approximately 2000 cm2. 
6.4. 
Dose Adjustment Criteria 
No dose adjustment will be made during this study. 
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6.5. 
Provisions for Remote Assessment Methods 
For publicly stated emergency situations where there are extenuating circumstances that prohibit 
physical visits to the clinical site or when the safety of subjects may be compromised by physical 
visits to the site, provisions for remote assessments have been addressed.  
For publicly stated emergency situations, the visit windows can be expanded as follows. 
Weeks 1 and 2 
± 5 days 
Week 4 
± 12 days 
Weeks 8, 12, 24 
± 14 days 
 
Refer to the Manual of Procedures for a list of those assessments; remote collection of certain 
clinical assessments may be allowed. 
6.6. 
Criteria for Study Stopping 
Subject enrollment will be stopped if any of the following SAEs occur: 
• Necrotizing soft tissue infection of th  study wound attributed to StrataGraft skin 
tissue 
• Severe acute hypersensitivity reaction attributed to StrataGraft skin tissue 
• Death attributed to StrataGraft skin tissue 
In the event that one of the listed SAEs occurs, the FDA and the local institutional review board 
(IRB) will be notified according to the decision tree for reporting SAEs as presented in the 
Manual of Procedures. The Medical Monitor will review the safety data associated with the 
adverse reaction with the clinical investigator and generate a summary narrative. The Medical 
Monitor, the Global Safety Lead, and the Clinical Trial Lead will conduct a comprehensive 
review of the safety data that will be submitted to the FDA prior to resumption of subject 
enrollment. 
An independent adhoc Safety Committee made up of DSMB members familiar with other 
StrataGraft studies will be on stand-by to serve as external adjudicators in the event that any of 
the prior listed SAEs occurs and study enrollment is halted. The Safety Committee working with 
the Medical Monitor, the Global Safety Lead and the Clinical Trial Lead will determine if and 
when the study may be restarted. 
 
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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
Subject-specific criteria: 
1. Men and women aged ≥ 18 years. 
2. Written informed consent. 
3. Sufficient healthy skin identified and designated as a donor site in the event that the 
StrataGraft treatment site requires autografting. 
4. 3% up to <50%TBSA of partial +/- full thickness thermal burns 
Treatment site-specific criteria: 
5. Thermal burn(s) with intact dermal elements for which excision and autografting are 
clinically indicated 
6. Total treatment areas no more than approximately 2000 cm2 and total tissues no more 
than 20 tissues. Total burn may consist of no more than 3 noncontiguous burn sites 
7. First excision and grafting of study treatment sites  
8. Thermal burn(s) on the torso, upper extremities, and lower extremities  
7.2. 
Subject Exclusion Criteria 
Subject-specific criteria: 
1. Pregnant women 
2. Prisoners 
3. Subjects receiving systemic immunosuppressive therapy at the time of injury 
4. Subjects with a known history of malignancy 
5. Pre-admission insulin-dependent diabetic subjects 
6. Subjects with concurrent conditions that in the opinion of the investigator may 
compromise subject safety or study objectives 
7. Expected survival of less than 3 months 
8. Participation in an interventional study of an investigational device, pharmaceutical, or 
biologic drug within 90 days prior to enrollment 
(Note: Participants in nutritional or non-interventional observational studies where no 
investigational product or device is given or administered will not be excluded.) 
Treatment site-specific criteria: 
9. Full-thickness burns 
10. Chronic wounds  
11. The face, head, neck, hands, feet, digits, buttocks, perineum/genitals, and areas over 
joints 
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12. Treatment sites immediately adjacent to unexcised eschar 
13. Clinical or laboratory determination of infection at the anticipated treatment sites at time 
of StrataGraft placement 
7.3. 
Subject Withdrawal Criteria 
Subjects are free to withdraw consent and discontinue participation in the study at any time. If a 
subject decides to discontinue participation, the reason(s) for discontinuation will be 
documented.  
Subjects discontinued from the study due to an AE will be followed until the AE has abated or is 
judged as clinically stable by the Investigator.  
A subject’s participation may be discontinued at any time at the discretion of the Investigator if 
the subject is uncooperative, is noncompliant, or the Investigator feels that it is in the subject’s 
best interest to be withdrawn from the study. Additionally, the subject may be considered lost to 
follow-up after 3 documented attempts are made to contact the subject. 
All study data from withdrawn or discontinued subjects will be retained and used in the final 
study analyses.  
In the event that a subject withdraws consent to participate in the study, the verbatim reason for 
withdrawal will be documented in the electronic case report form (eCRF). The subject will be 
asked to complete the current study evaluations but will be instructed that they are under no 
obligation to complete the study and are free to decline. The subject will be informed that they 
may be recontacted in the future by the study staff. At the time of withdrawal, a request for 
permission to review the subject’s medical records at the 24-week time point will be made to 
check their status and for completion of study reporting forms. If the subject agrees to allow 
review of their medical records, they will sign a new Health Insurance Portability and 
Accountability Act authorization. Data collected under informed consent will be retained and 
included in the data analysis. If the subj ct indicates that their collected samples may no longer 
be used for the study, all retained unprocessed samples being held for analysis will be destroyed. 
However, archival samples that were collected per required agency regulations will be retained 
as required by regulations. 
All subjects who discontinue from the study for any reason will be requested to provide contact 
information for the purpose of participation in a long-term follow up Registry Study. Subjects 
with closed wounds who complete the study will also have the opportunity to participate in the 
Registry Study and the consent form will be offered at the confirmation of healing visit. For 
those subjects whose wounds do not heal, they too would be offered the opportunity to 
participate in the Registry Study and the consent form will be offered during the study period. 
 
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8. 
TREATMENT OF SUBJECTS 
8.1. 
Description of Study Treatment 
The study treatment is described in Table 3.  
Table 3: 
Investigational Product 
Product Name: 
StrataGraft skin tissue 
Dosage Form/Physical Description: 
StrataGraft skin tissue is an off-white rectangular 
sheet of approximately 100 cm2 (approximately 
8 cm by 12.5 cm), consisting of a viable, 
bioengineered, regenerative skin construct 
derived from human keratinocytes grown on 
gelled collagen containing human dermal 
fibroblas s. StrataGraft skin tissue is stored at  
-70°C to -90°C until thawed for use. The hold 
solution that must be used with the StrataGraft 
skin tissue must be stored at 2° to 8°C until 
required for surgery.  
Dosage 
One application of sheets of no more than 20 
StrataGraft skin tissues and applied to no more 
than 3 noncontiguous burn sites and applied to no 
more than approximately 2000 cm2 total burn area 
to wounds with intact dermal elements 
Route of Administration 
StrataGraft skin tissue is applied topically to 
thermal burns that have been surgically excised to 
remove nonviable tissue. It is meshed up to 1:1, 
placed onto the wound bed, trimmed to fit the 
wound as necessary, and secured in place. 
Manufacturer 
Stratatech, a Mallinckrodt Company 
 
8.2. 
Concomitant Medications 
All concomitant medications, including the use of antibiotics, must be recorded in the eCRF after 
the consent form is signed and throughout the study period. Systemic and topical 
antibiotics/antimicrobials may be used at the discretion of the clinical investigator with the 
exception of sulfamylon and silver-containing antimicrobials and silver-containing dressings. 
The use of sulfamylon and silver containing/releasing antimicrobials and dressings is not 
recommended as they are thought to interfere with the viability of the living cells in StrataGraft 
skin tissue. Prior to StrataGraft skin tissue placement, chlorhexidine can be applied to burn sites 
for wound preparation but must be thoroughly rinsed off prior to StrataGraft placement. After 
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StrataGraft skin tissue placement, further use of this antiseptic on the StrataGraft treatment site is 
also not recommended. Use of any of the aforementioned antiseptics at the discretion of the 
Principal Investigator, after StrataGraft skin tissue placement, would not be considered a 
protocol deviation. Additionally, investigational agents may not be used for the duration of study 
period. All other concomitant medications are unrestricted. Intravenous fluids generally used to 
maintain hydration and general anesthetic given during surgery need not be captured as 
concomitant medications.  
8.3. 
Concomitant Procedures 
Any concomitant procedure (including transfusions, use of xenogenic or allogeneic products, 
negative pressure wound therapy, etc.) must be recorded in the eCRF after the consent form is 
signed and throughout the duration of the study.  
8.4. 
Randomization and Blinding 
This study is designed as an open-label, single arm study in whi h all subjects receive 
StrataGraft skin tissue and all other burn wounds will be treat d per institutional SoC. No 
randomization will be conducted, and no blinding is required for the study. 
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9. 
STUDY DRUG MATERIALS AND MANAGEMENT 
9.1. 
Study Treatment 
StrataGraft® skin tissue 
9.2. 
Study Treatment Packaging and Labeling 
See Investigator’s Brochure  
9.3. 
Study Treatment Storage 
StrataGraft skin tissue is stored in a freezer at -70°C to -90°C. 
9.4. 
Study Treatment Preparation 
See Manual of Procedures: Patient Kit Receipt and StrataGraft Skin Tissue Thaw Instructions 
9.5. 
Study Administration 
Once the designated study site(s) have been excised and the subject is determined to meet all 
eligibility criteria, StrataGraft skin tissue will be meshed up to 1:1 and secured to the wound with 
sutures, staples, or tissue adhesives and then dressed with a non-adherent, porous dressing. 
Secondary dressings will be applied that are designed to maintain a moist wound environment 
and protect tissue from maceration and external contamination.  
Silver-containing dressings are not recommended for use in this study. No adhesive dressing, 
tape, or adhesive strips, may be applied directly on the StrataGraft skin tissue-covered site or its 
periphery during the study period. Prior to StrataGraft skin tissue placement, chlorhexidine can 
be applied to burn sites for wound preparation but must be thoroughly rinsed off before 
StrataGraft placement. After StrataGraft skin tissue placement, further use of this antiseptic is 
not recommended. 
It is not expected that StrataGraft skin tissue will incorporate into the wound bed due to vascular 
ingrowth as is seen with autologous skin grafts. It is anticipated that maximal benefit from 
treatment with StrataGraft skin tissue would come after maintenance of contact with the clean 
wound bed for as long as possible. Therefore, it is important to be careful during dressing 
changes during the first few weeks following placement. 
Week 1: The non-adherent porous contact layer dressing should remain anchored in place for at 
least 3 days in order to prevent dislodging of the StrataGraft skin tissue. This non-adherent layer 
may or may not be replaced at the discretion of the Investigator. The frequency of changes of the 
secondary dressings is at the discretion of the Investigator paying attention to the precautions 
listed below. 
Weeks 2 to 3: The contact layer dressing may be removed with care not to dislodge any 
remaining adherent StrataGraft skin tissue. Replacement of a nonadherent contact layer is 
recommended. All secondary dressings and frequency of changes are at the discretion of the 
Investigator paying attention to the precautions listed below. The healing epidermis beneath 
StrataGraft skin tissue may result in small areas of drying and lifting of StrataGraft changing the 
appearance to one that may be described as shabby or flaky. Over time, the dried StrataGraft skin 
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tissue will flake off during daily washing and wound care per institutional standard of care as the 
new, healthy epidermis expands beneath it. The healing wound still requires protection from 
shear forces as the new skin matures. 
Week 4 through remainder of study: All dressings will be changed per institutional SoC until 
healing, or as long as deemed clinically necessary by the Investigator.  
9.6. 
Study Treatment Handling and Disposal 
See Manual of Procedures: Patient Kit Receipt Instructions, Chain of Custody Document 
Examples, and Record of Shipment Document Examples. 
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10. 
ASSESSMENT OF OTHER PRE-SPECIFIED ENDPOINTS 
Wound closure 
Complete wound closure is defined as 100% skin re-epithelialization in the absence of drainage. 
Successful wound closure in this study requires that complete wound closure is achieved without 
autograft placement and is confirmed at least 2 weeks following the initial observation of 
complete closure. The clinical investigator will evaluate treatment site(s), assess the proportion 
of the treated wound closed, complete wound closure, and confirmation of complete wound 
closure either by direct clinician observation or by subject-provided photo-documentation per 
Schedule of Assessments (Section 6.1.1).  
Photo-documentation 
Photographs will be taken by the clinician to supplement clinical assessment of percentage 
epithelialization, complete wound closure, confirmed wound closure, durable wound closure and 
the POSAS assessments (eg, appearance and cosmesis) of the treatment sites. Photographs taken 
and submitted by the subject (or other person designated by the subject) may be used for 
evidence of wound characteristics if a visit is missed or for a  unscheduled visit. 
Photo-documentation is submitted by the subject beginning at discharge then weekly until Week 
12 and then every other week until Week 24. These subject-submitted photos are only possible if 
the Principal Investigator gives approval for the subject to take off their dressings at home. In the 
event the dressings are not allowed to be changed at home, no subject photos will be expected or 
required. Photos submitted during weeks when there are no in-person visits would serve as an 
allowable proxy for observing wound characteristics. If a subject’s wound is noted to be closed 
for the first time via a submitted photo, that photo should trigger the scheduling of a visit 2 
weeks later for confirmation of wound healing. See Manual of Procedures for specific 
instructions regarding the methodology for obtaining photographs. 
10.1. 
Other Endpoints 
Assessments will be documented to determine other endpoints: 
• Proportion of subjects with confirmed wound closure without autograft placement (ie, 
complete re-epithelialization without drainage and subsequently verified with 
confirmation assessment) on or before Week 12 and supported by 
photo-documentation 
• Proportion of subjects with confirmed wound closure without autograft (verified with 
confirmation assessment) at each visit and supported by photo-documentation 
• Proportion of subjects without autografting who maintain durable wound closure by 
Week 24 
• Time to confirmed wound closure without autografting (verified with confirmation 
assessment) 
• Treatment site skin quality data: The total observed POSAS by clinician and by 
subject. Per site descriptive statistics will be presented separately for clinician and 
subject values for each of the individual POSAS items and the total POSAS score, 
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represented as the mean score across all treatment sites and supported by photo 
documentation 
• Number (%) of subjects with wound infection-related events 
 
10.2. 
Exploratory Endpoints 
HCRU Assessments 
Assessments will be documented for the following as exploratory endpoints: 
• Location of care for StrataGraft application (eg, inpatient hospital, 
outpatient/ambulatory hospital, clinic, etc.) 
• Treatments used for all other burn areas following excision and %TBSA treated with 
each (other than StrataGraft treatment sites) 
• Number of OR procedures required for burn treatment: excisions, application of 
StrataGraft tissue and all other grafting procedures, including autografts and 
xenografts  
• Duration of each OR procedure  
• Length of hospital stay  
• Prescription drugs given at discharge from the hospital for wound-related events 
including pain control, itch, psychotropics, and antibiotics  
• Re-admission within 30 days after discharge 
• Whether a re-admission is planned 
• Length of hospital stay of e-admission 
10.3. 
Subgroup Analyses 
Subgroup Assessments 
Subgroup analyses will include the following categories: 
• Sex  
• Race (white, non-white) 
• Ethnicity (Hispanic, non-Hispanic) 
• Age (< 65, ≥ 65) 
• Size of area treated with StrataGraft (≤ 500 cm2, > 500 cm2) 
• Overall TBSA of wound burden (burn areas plus donor site area; < median, 
≥ median) 
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11. 
OTHER ASSESSMENTS 
A subset of 10 subjects with closed wounds (from subjects who have achieved wound closure, 
across all the  clinical sites) will be separately consented to have a punch biopsy (measuring 3 
mm) taken from the center of the healed burn wound, and another punch biopsy measuring 3 mm 
taken from non-burned healthy skin. A histological evaluation of both samples will be done to 
analyze and contrast the skin architecture in the healed burn wound with healthy skin. The 
biopsy will occur at the study visit Week 12, regardless of when wound closure occurs. 
Wound assessments will include measurements for average depth, length, and width for 
calculations of area and percent epithelialization. Wound assessments will be facilitated by 
photographs taken by the subject and/or taken by the clinical study site staff at study visits 
throughout the study.  
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12. 
SAFETY ASSESSMENT  
Safety will be monitored from the time of subject signing consent to participate in the study and 
includes: TEAEs, treatment-emergent SAEs, local wound infections, systemic infections, vital 
signs, and deaths throughout the study duration. In addition to the collection of common clinical 
study safety data, blood samples (blood plasma and leucocytes) will be collected to comply with 
the archival xenotransplantation FDA requirements. 
12.1. 
Primary Safety Endpoint 
The primary objective of this study is to demonstrate the safety of a single application of 
StrataGraft skin tissue in the post excision treatment of thermally induced DPT burns that 
contain intact dermal elements. The primary safety endpoint is the count and percentage of 
subjects with TEAEs. 
 
Primary Outcome Measure: 
Title:  
Number of subjects with TEAEs 
 
Description: 
Total count of participants observed with TEAEs during the study 
 
Timeframe: 
Approximately 24 weeks 
 
12.2. 
Safety Parameters Specific to Therapeutic Category 
12.2.1. 
Incidence of infection 
Local wound infection will be determined by the clinical investigator and may include 
confirmatory microbiological assessment. Similarly, systemic infection will be determined by the 
clinical investigator and may include documentation of such signs as positive blood cultures, 
fever (defined as >38.5oC) and/or elevated white blood cell count.  
Study treatment sites will be examined by the investigator for signs and symptoms of infection at 
every study visit. Cultures of the treatment sites may be obtained for microbiological evaluation 
at the discretion of the clinical investigator or per institutional SoC at any time during treatment. 
The clinical investigator will evaluate the wound culture results for clinical significance. 
Infections and their treatment must be documented in the eCRF with notation of 
StrataGraft-treated site or “Other” (ie, SoC treatment). 
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12.2.2. 
Archival plasma and leukocyte samples 
In accordance with current xenotransplantation FDA Guidance, an archival blood sample will be 
collected at Day 1 (Baseline) prior to StrataGraft skin tissue placement and retained. For further 
detail, see Manual of Procedures, Subject Plasma and Leukocyte Archival. 
12.2.3. 
Immunology 
Blood collection for PRA testing (HLA I and II) will be conducted at Day 1 (Baseline), Week 4, 
and Week 12. 
12.2.4. 
Regrafting and Delayed Wound Healing 
In the event that a StrataGraft-treated area needs to be regrafted with either an autograft or a 
xenograft after prior treatment with StrataGraft skin tissue, the event would not be marked as an 
AE, but rather as a failure to close. In the event that there is an accompanying wound 
degradation event occurring simultaneously such as infectio  that results in delayed wound 
healing, the delayed wound healing secondary to the ongoing inf ction can be listed as an AE or 
SAE as applicable. If that infective process eventually w rrants regrafting, the regrafting should 
still be marked as a failure to close and not an AE. 
12.3. 
Standard Safety Parameters 
12.3.1. 
Demographic/Social/Medical History 
Past medical history, social, and acute medical history will be collected at Screening. Medical 
history will be reviewed for eligibility for enrollment into the study as described in the inclusion 
criteria. 
12.3.2. 
Vital Signs 
Vital signs (blood pressure, p lse rate, temperature) will be measured at each scheduled study 
time point. The change from baseline will be calculated for each study time point for clinical 
safety analyses. 
12.3.3. 
Weight and Height 
Weight and height will be measured at Screening.  
12.3.4. 
Physical Examination 
The limited Physical Examination will be conducted at Screening to include evaluation of lungs, 
heart, abdomen, and extremities. The findings of the physical examination will be recorded on 
the eCRF. 
12.3.5. 
Laboratory Assessments 
Laboratory safety parameters will be evaluated for clinically significant changes within this 
subject population at Baseline, defined study intervals, and as deemed appropriate by the 
clinician according to the institutional SoC in the evaluation of study subjects.  
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12.3.5.1. Hematology 
Hematology evaluations will include hemoglobin, platelets, red blood cell count and white blood 
cell count with differential. 
12.3.5.2. Blood Chemistry 
Blood chemistry assessments will include alanine transaminase, aspartate transaminase, and 
bilirubin, glucose, electrolytes, and creatinine. 
12.3.5.3. Immunology Assessments 
Immunological evaluations will include PRA with HLA class I and II screening and testing for 
allelic reactivity. 
12.3.5.4. Pregnancy Testing 
A serum pregnancy test for women of child-bearing potential will be performed at Screening 
using the local laboratory. Should a pregnancy be confirmed after placement of StrataGraft, the 
pregnancy will be reported as a special event (ie, not an AE). Since StrataGraft skin tissue is a 
single application, the subject will continue with all scheduled study evaluations. Pregnant 
subjects will be followed until post-partum and the outcome of the pregnancy will be reported. 
12.4. 
Adverse Events and Serious Adverse Events 
Definition of Adverse Events 
An AE is the development of an undesirable medical condition or the deterioration of a 
pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered casually related to the product. In clinical studies, an AE can include 
an undesirable medical condition occurring at any time, including Baseline or washout periods, 
even if no study treatment has been administered. 
All AEs that occur after any subject has signed the consent form and the AEs occurring during 
treatment must be recorded on forms provided by the Sponsor, whether or not they are related to 
the study. 
Definition of SAE 
An SAE is an AE occurring during any part of the study period (ie, Baseline, treatment, washout, 
or follow-up), and at any dose of the investigational product, comparator or placebo, that fulfills 
one or more of the following: 
• Results in death; all AEs with an outcome of death must be reported as SAEs. The 
Investigator should make every effort to obtain and send death certificates and 
autopsy reports to the Sponsor or designee, or state “not available.” 
• It is immediately life-threatening 
• It requires inpatient hospitalization or prolongation of existing hospitalization 
• It results in persistent or significant disability or incapacity 
• Results in a congenital abnormality or birth defect 
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• It is an important medical event that may jeopardize the subject or may require 
medical intervention to prevent one of the outcomes listed above. 
12.5. 
Intensity of Adverse Event  
Intensity will be assessed according to the following scale: 
• Mild (awareness of sign or symptom, but easily tolerated) 
• Moderate (discomfort sufficient to cause interference with normal activities) 
• Severe (incapacitating, with inability to perform normal activities) 
It is important to distinguish between serious and severe AEs. Severity is a measure of intensity 
of an AE, whereas seriousness is defined by the criteria under Section 12.4. An AE of severe 
intensity may not always be considered an SAE. 
12.6. 
Relationship to Study Drug 
An Investigator who is licensed to practice medicine must make the determination of relationship 
to the investigational product for each AE (unrelated, possibly related or probably related). The 
Investigator should decide whether, in his or her medical judgment, there is a reasonable 
possibility that the event may have been caused by the investigational product. If no valid reason 
exists for suggesting a relationship, then the AE should be classified as “unrelated.” If there is 
any valid reason, even if undetermined, for suspecting a possible cause-and-effect relationship 
between the investigational product and the occurrence of the AE, then the AE should be 
considered “related.” 
If the relationship between the AE/SAE and the investigational product is determined to be 
“possible” or “probable”, the event will be considered to be related to the investigational product 
for the purposes of expedited regulatory reporting. 
12.7. 
Other Adverse Event  
The Drug Safety Physician and  if applicable, the Clinical Study Team Physician will identify 
other adverse event(s) during the evaluation of safety data for the Clinical Study Report. 
Significant adverse events of particular clinical importance will be collected as adverse events of 
special interest, ie, events other than SAEs and those AEs leading to discontinuation of the 
subject from the study). For each adverse event of special interest, a narrative may be written and 
included in the clinical study report. 
12.8. 
Pregnancy Events 
Should a pregnancy occur, it must be reported and recorded on the Sponsor’s pregnancy form. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that an investigational 
product may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality/birth defects) must be recorded on the eCRF, even if the subject is 
discontinued from the study. Elective abortions without complications are not considered an AE 
and are not reported as an AE. 
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All reports of congenital abnormalities/birth defects, spontaneous miscarriages, and serious 
complications due to pregnancy should be reported as SAEs.  
In this study, subjects will not be discontinued from the study unless the subject elects to 
withdraw consent. 
12.9. 
Recording Adverse Events 
Adverse events spontaneously reported by the subject and/or in response to an open question 
from the study personnel or revealed by observation will be recorded during the study at the 
investigational site. Clinically significant changes in laboratory values, blood pressure, and pulse 
rate need not be reported as AEs. However, abnormal values that constitute an SAE, are 
associated with an SAE, or lead to discontinuation of administration of study treatment must be 
reported and recorded as an AE. Information about AEs will be collected from the signing of 
consent form until the end of the study. All SAE information will be collected from the signing 
of consent form and throughout the study follow-up period. The AE terms should be reported in 
standard medical terminology when possible. For each AE  the i vestigator will evaluate and 
report the onset (date and time), resolution (date and time), intensity, causality, action taken, 
serious outcome (if applicable), and whether or not it caused the subject to discontinue the study. 
12.10. 
Reporting Adverse Events 
All SAEs (related and unrelated) will be recorded from the signing of consent form until 
following the end of treatment exposure. All SAEs must be reported to Sponsor within 1 
business day of the first awareness of the ev nt. The Investigator must complete, sign and date 
the SAE pages, verify the accuracy of the information recorded on the SAE pages with the 
corresponding source documents, and s nd a copy by fax to the Sponsor.  
Additional follow-up information  if required or available, should all be faxed to the Sponsor 
within 1 business day of receipt and this should be completed on a follow-up SAE form and 
placed with the original SAE inf rmation and kept with the appropriate section of the eCRF 
and/or study file. 
The Sponsor is responsible for notifying the relevant regulatory authorities of certain events. It is 
the Principal Investigator’s responsibility to notify the IRB or Independent Ethics Committee 
(IEC) of all SAEs that occur at his or her site. Investigators will also be notified of all 
unexpected, serious, treatment-related events (7/15 Day Safety Reports) that occur during the 
clinical study. Each site is responsible for notifying its IRB or IEC of all SAEs. 
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13. 
STATISTICS 
13.1. 
Sample Size Determinations 
No sample size determination was made for this study, as this is 1 treatment group, non-
randomized study designed to accumulate supplemental safety and efficacy data for the use of 
StrataGraft for the treatment of DPT wounds with intact dermal elements. This study will enroll 
approximately 100 subjects from up to 18 clinical study centers that previously participated in 
the prior Phase 3 study. 
13.2. Analysis Populations 
Screen failures are defined as subjects who consent to participate in the clinical study but were 
not subsequently treated with StrataGraft skin tissue. 
The modified intention-to-treat (mITT) population will include all subjects who enrolled and 
received StrataGraft skin tissue. The safety and efficacy analyses will be based on the mITT 
population. 
13.3. 
Statistical Analysis 
This section provides a general summary of the statistical methods to be used in analyzing study 
data. A more detailed statistical analysis plan will be provided in a separate document that will 
be finalized prior to database lock. 
Descriptive statistics for continuous variables will include the mean, median, standard deviation, 
minimum value, and maximum value. Categorical data will be summarized by counts and 
percentages. 
Assessments of photographs of burn sites will be used as confirmatory evidence of durable 
closure in cases of absence of an in-person visit and for weeks where an in-person visit is not 
scheduled. 
All data documented in the eCRFs and laboratory test results, including repeated and 
unscheduled assessments, will be presented in data listings.  
13.3.1. 
Primary Safety Endpoint Analysis 
The primary endpoint analysis will be count and percent of subjects with TEAEs. This endpoint 
will be analyzed based on the mITT population. 
13.3.2. 
Other Pre-specified Endpoint Analyses 
For this study, confirmed wound closure is defined as meeting wound determinations at 2 visits:  
1. First, a visit at which the clinician determined complete (100%) re-epithelialization 
without drainage 
2. Second, an assessment at a subsequent visit that is at least 2 weeks later than the first visit 
and wound closure was confirmed (ie, determined again) to be completely closed 
Durable wound closure is achieved when a wound is observed as remaining closed at least 
3 months after complete wound closure.  
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The clinician may determine confirmed wound closure and durable closure either by directly 
observing the wound or by assessing appropriate photo-documentation that will be provided 
electronically by the subject weekly for the first 12 weeks and then provided every other week 
through to Week 24. The following endpoints will be analyzed with descriptive statistics with 
95% confidence intervals: 
• Proportion of subjects with confirmed wound closure without autograft placement (ie, 
complete re-epithelialization without drainage and subsequently verified with 
confirmation assessment) on or before Week 12 and supported by photo-
documentation 
• Proportion of subjects with confirmed wound closure without autograft (verified with 
confirmation assessment) at each visit and supported by photo-documentation 
• Proportion of subjects without autografting who maintain durable wound closure by 
Week 24 
• Time to confirmed wound closure without autografting (verified with confirmation 
assessment) 
• Treatment site skin quality data: The total observed POSAS by clinician and by 
subject. Per site descriptive statistics will be presented separately for clinician and 
subject values for each of the individual POSAS items and the total POSAS score, 
represented as the mean score across all treatment sites and supported by 
photo-documentation 
• Number (%) of subjects with wound infection-related events 
The time to first confirmed wound closure (verified with confirmation assessment) will be 
analyzed by the Kaplan-Meier estimation method. The period for this analysis is calculated as 
(the date of having the first event  the date of Day 1 + 1). Subjects not having any event during 
the study will have their time censored at the last available date in the study. Kaplan-Meier 
estimates by StrataGraft treatment area with confirmed wound closure will be presented for the 
following categories: ≤ 500 cm2, > 500 cm2. 
13.3.3. 
Exploratory Efficacy Endpoints 
Results from all HCRU parameters as exploratory efficacy endpoints will be summarized with 
descriptive statistics by visit:  
• Location of care for StrataGraft application (eg, inpatient hospital, 
outpatient/ambulatory hospital, clinic, etc.) 
• Treatments used for all other burn areas following excision and %TBSA treated with 
each (other than StrataGraft treatment sites) 
• Number of OR procedures required for burn treatment: excisions, application of 
StrataGraft tissue and all other grafting procedures, including autografts, allografts, 
and xenografts 
• Duration of each OR procedure  
• Length of hospital stay  
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• Prescription drugs given at discharge from the hospital for wound-related events 
including pain control, itch, psychotropics, and antibiotics 
• Re-admission within 30 days after discharge 
• Whether re-admission is planned 
• Length of hospital stay of re-admission 
13.3.4. 
Subgroup Analyses 
The complete wound closure and TEAE endpoints will be summarized by the following 
demographic and baseline characteristics: 
• Race (white, non-white) 
• Ethnicity (Hispanic, non-Hispanic) 
• Age (<65, ≥ 65) 
• Sex (Male, Female) 
• StrataGraft size of the area (≤ 500 cm2, > 500 cm2)  
• Overall TBSA of wound burden defined as burns plus donor site area (< median, 
≥ median)  
13.3.5. 
Multiple Comparison Testing Methods 
Adjustment for multiplicity does not apply to nalysis of the endpoints for this study. 
13.3.6. 
Interim Analyses 
No statistical interim analyses for fficacy are planned for this study. 
13.3.7. 
Safety Analysis 
The primary safety endpoint analysis will be count and percent of subjects with TEAEs and will 
be based on mITT population. 
No formal hypothesis testing will be performed for any safety variables. All safety variables will 
be summarized with descriptive statistics. 
Adverse Events 
The TEAE is defined as those adverse events with onset date and time after the first placement of 
study product or those events in which the onset date and time are before the first placement of 
study product but worsened after the first placement of study product. Coding of adverse events 
will be performed using the Medical Dictionary for Regulatory Activities classification system. 
The number (%) of TEAE of subjects who experienced at least 1 TEAE will be summarized by 
system organ class and by preferred term. The TEAEs will also be summarized by maximum 
severity and by strongest relationship to StrataGraft skin tissue. The TEAEs on study treatment 
sites (StrataGraft skin tissue-treated sites) and other nonstudy treatment (SoC-treated sites) will 
be summarized by system organ class and by preferred term; SAE will be tabulated and listed in 
a manner similar to TEAE. 
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Infection 
The incidence of infection of the study treatment sites will be presented.  
Vital Signs 
Vital signs (blood pressure, pulse rate, temperature) will be calculated and presented at each 
scheduled time point, as will the change from Baseline. 
Safety Laboratory Parameters 
Safety laboratory tests (including creatinine and complete blood count with differential) will be 
calculated and presented at each scheduled time point, as will the change from Baseline. 
Safety laboratory test results will be categorized and presented as “Low,” “Normal” and “High”, 
as defined by the sites’ laboratory normal range. Additionally, shift tables will be presented 
summarizing changes from normal to out-of-normal range. 
13.3.8. 
Handling of Missing Data 
No imputation for missing values will be conducted. All obs rved values (ie, excluding missing 
values for visit) will be used for the analyses.  
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14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1. 
Study Monitoring 
Before an investigational site can enter a subject into the study, a representative of the Sponsor 
will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of the Sponsor or its representatives. This 
will be documented in a Clinical Study Agreement between the Sponsor and the 
investigator. 
During the study, a monitor from the Sponsor or representative will have regular contacts with 
the investigational site, for the following: 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks 
are being performed 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the subject’s medical records t the hospital or practice, and other records relevant to 
the study. This will require direct access to all original records for each subject (eg, 
medical records). 
• Record and report any protocol deviations not previously sent to the Sponsor. 
• Confirm AEs and SAEs have been properly documented on eCRFs and confirm any 
SAEs have been forward d to the Sponsor and those SAEs that met criteria for reporting 
have been forwarded to the IRB. 
The monitor will be available between visits if the investigator(s) or other staff needs 
information or advice. 
14.2. 
Audits and Inspections 
Authorized representatives of the Sponsor, a regulatory authority, an IEC or an IRB may visit the 
site to perform audits or inspections, including source data verification. The purpose of a 
Sponsor audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
International Council for Harmonisation, and any applicable regulatory requirements. The 
investigator should contact the Sponsor immediately if contacted by a regulatory agency about 
an inspection. 
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14.3. 
Monitoring Boards 
The Principal Investigator must obtain IRB approval for the investigation. All IRB approvals, 
and all materials approved by the IRB for this study including the subject consent form and 
recruitment materials must be maintained by the Investigator and made available for inspection. 
Additionally, an independent adhoc Safety Committee will ensure adequate protection of the 
safety of subjects. The Committee’s objectives, composition, and operational details of its 
activities will be defined in the Safety Committee Charter. 
In the event that an SAE occurs such that stopping the study is considered, the local IRB will be 
notified as presented in the Manual of Procedures. 
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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance audit. Please see Section 14.2 for more details regarding the audit 
process. 
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16. 
ETHICS 
16.1. 
Ethics Review 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB or IEC, as appropriate. The 
investigator must submit written approval to the Sponsor before he or she may enroll any subject 
into the study. In addition, the IRB or IEC must approve all advertising used to recruit patients 
for the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. Any amendment made to this protocol must be 
reviewed and approved by the IRB or IEC. 
The Principal Investigator is also responsible for providing the IRB with reports as local 
regulations require, including any reported serious adverse treatment reactions arising from any 
other study conducted with the investigational product. The Sponsor will provide this 
information to the Principal Investigator. 
16.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that are consistent with ICH 
GCP, which has its ethical foundation in the Decl ration of Helsinki and are consistent with 
applicable regulatory requirements. 
16.3. 
Written Informed Consent 
The Principal Investigator(s) at each study site will ensure that the subject is given full and 
adequate oral and written information bout the nature, purpose, possible risk, and benefit of the 
study. Subjects must also be notified that they are free to discontinue from the study at any time. 
The subject should be give  the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed Informed Consent Form. A copy 
of the signed Informed Consent Form must be given to the subject. 
Consent must also be obtained for direct contact by Sponsor for the post study safety registry 
during the study period. 
 
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17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
The Sponsor will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
study treatment storage area, study treatment stocks, study treatment accountability records, 
subject medical records and study source documents, and other records relative to study conduct. 
17.2. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for the Sponsor or the 
Regulatory Authority to review any documentation relating to the study, the Investigator must 
permit access to such records. 
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18. 
LIST OF REFERENCES 
1. American Burn Association. National Burn Repository 2017 Report of Data from 2008‐
2017. Chicago, IL: American Burn Association, Dataset Version 13.0. 
2. Bloom ET. January 13, 2000. Xenotransplantation Subcommittee. Division of Cellular 
and Gene Therapies, Office of Therapeutics Research and Review, FDA/CBER.  
3. Burn Incidence and Treatment in the United States: 2016; 2016. accessed June 4, 2020. 
http://ameriburn.org/who-we-are/media/burn-incidence-fact-sheet/ 
4. FDA. Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues 
Concerning the Use of Xenotransplantation Products in Humans. December 2016. 
5. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S. A comparison of 
conservative versus early excision therapies in severely burned patients. Ann Surg 1989; 
209(5):547-52. 
6. Muller MJ, Herndon DN. The challenge of burns. Lancet 1994;343:216–20. 
7. Munster AM, Smith-Meek M, Sharkey P. The effect of early surgical intervention on 
mortality and cost-effectiveness in burn care, 1978-91. Burns 1994; 20:61–4. 
 
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Signature Page for VV-CLIN-025428 v4.0
Signature Page for VV-CLIN-025428 v4.0
Approval
Clinical
02-Oct-2020 18:43:11 GMT+0000
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