A Phase III Open-label, Controlled, Randomized, Multicenter Study Evaluating the Efficacy and Safety of StrataGraft Skin Tissue in Promoting Autologous Skin Tissue Regeneration of Complex Skin Defects Due to Thermal Burns That Contain Intact Dermal Elements and for Which Excision and Autografts Are Clinically Indicated
Phase: PHASE3
Conditions: Burn, Thermal
Sponsor: Stratatech, a Mallinckrodt Company

35235,(7$5<$1'&21),'(17,$/
A PHASE III OPEN-LABEL, CONTROLLED, RANDOMIZED, MULTICENTER 
STUDY EVALUATING THE EFFICACY AND SAFETY OF STRATAGRAFT® 
SKIN TISSUE IN PROMOTING AUTOLOGOUS SKIN TISSUE 
REGENERATION OF COMPLEX SKIN DEFECTS DUE TO THERMAL BURNS 
THAT CONTAIN INTACT DERMAL ELEMENTS AND FOR WHICH EXCISION 
AND AUTOGRAFTS ARE CLINICALLY INDICATED 
STRATA2016 
PHASE III CLINICAL PROTOCOL 
Original Protocol (V 1.0) Dated September 14, 2016 
Amendment 1 (V2.0) Dated 30 May 2019 
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Acceptance of this document constitutes the agreement by the recipient that no unpublished 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 Stratatech, except that this document may be disclosed to appropriate institutional review 
boards/ethical committees so long as they are requested to maintain its confidentiality. 
/$5

Stratatech, A Mallinckrodt Company 
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APPROVAL STATEMENT 
The sponsor below has approved this protocol and pledges that this study will be conducted 
according to all stipulations of the protocol as specified in both the clinical and administrative 
sections, including all statements regarding confidentiality.  By completing and signing the 
Clinical Protocol Approval letter and Form FDA-1572 “Statement of Investigator”, the clinical 
investigator agrees to abide by United States federal regulations, applicable state regulations, 
and the study protocol during the course of the clinical trial conducted under an Investigational 
New Drug application.   
SPONSOR: 
STRATATECH, a Mallinckrodt Company 
510 Charmany Drive 
Suite 150 
Madison, WI  53719 
Approved by:      _________________________________ 
 MD 
Senior Director, Medical Affairs 
Date:______________ 

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SUMMARY OF STRATA2016 PROTOCOL 
TITLE OF STUDY 
A Phase III Open-Label, Controlled, Randomized, Multicenter Study Evaluating the Efficacy and 
Safety of StrataGraft Skin Tissue in Promoting Autologous Skin Tissue Regeneration of Complex 
Skin Defects Due To Thermal Burns That Contain Intact Dermal Elements and For Which 
Excision and Autografts Are Clinically Indicated  
CLINICAL PHASE 
Phase III. 
STUDY OBJECTIVE 
The objective of this study is to assess the efficacy and safety of a single application of 
StrataGraft tissue in the treatment of complex skin defects caused by thermal burns that 
contain dermal elements and for which surgical excision and autografts are clinically 
indicated.  
STUDY RATIONALE AND DESIGN 
The current standard of care (SOC) for severe burns and other complex skin defects is surgical 
excision of a sheet of healthy skin from an uninjured site on the patient and transplantation of 
this autologous skin graft to the primary injury after excision of nonviable tissue.  While this 
process can be effective in providing closure to the original wound, it is associated with 
significant morbidity due to the iatrogenic donor site wound created from surgical excision of 
the autograft tissue that is then transplanted to the original wound.  These donor site wounds 
are extremely painful, are prone to scarring, dyspigmentation and infection, are associated with 
a physiologic burden, and can convert to full-thickness wounds that must then be managed.  In 
addition, the amount of healthy skin available for autograft transplantation is frequently 
limiting in patients with large burns, necessitating sequential reharvesting of available donor 
sites.  As a result of these limitations, there is an urgent need for alternatives to the practice of 
donor site harvest and autograft treatment of severe burns and other complex skin defects. 
The STRATA2016 phase III study is designed to evaluate whether treatment with StrataGraft 
skin tissue can promote the healing of complex skin defects due to thermal burns that contain 
intact dermal elements and for which surgical excision and autografts are indicated. 
StrataGraft skin tissue is an off-the-shelf, biologically active human skin substitute which is 
anticipated to provide immediate wound coverage, aid in wound bed conditioning, and 
promote autologous tissue regeneration and durable wound closure while reducing the amount 
of donor tissue harvested.  It is anticipated that StrataGraft skin tissue will remain in the wound 
long enough to promote autologous tissue regeneration and be replaced over time by the 
subject’s own cells rather than permanently engrafting.   

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Stratatech has completed STRATA2001, a first-in-human, dose escalation trial evaluating the 
safety of a single application of StrataGraft skin tissue in subjects with full-thickness complex 
skin defects of 5 to 73% total body surface area (TBSA) resulting from thermal injury, trauma, or 
necrotizing fasciitis.  In STRATA2001, full-thickness wounds were temporized for 7 days with 
StrataGraft skin tissue or cadaver allograft prior to autografting.  Autograft take was 
comparable in wounds temporized with StrataGraft tissue as compared to cadaver allograft. 
There were no changes in the types of adverse events (AEs) as the dosage of StrataGraft skin 
tissue was increased 5-fold across the cohorts from 44 cm2 to 220 cm2, and no AEs were 
product-related.  StrataGraft tissue remained intact and viable throughout the 7-day placement 
period, suggesting the potential for continued biological activity during longer placement. 
The STRATA2011 study, a follow-up to the STRATA2001 trial, was conducted as an open-label, 
dose-escalation, multicenter study evaluating the safety, tolerability, and efficacy of longer 
exposure to increasing amounts of StrataGraft skin tissue in promoting the healing of complex 
skin defects containing intact dermal elements.  In STRATA2011, a single application of 
StrataGraft skin tissue was applied to deep partial-thickness burns and left in place to evaluate 
whether StrataGraft skin tissue promoted autologous tissue regeneration while reducing or 
eliminating the need for the surgical harvesting of donor sites for autografts. 
The STRATA2011 study included subjects with thermal burns containing intact dermal elements 
and whose area of total injury ranged from 3 to 49% TBSA.  Each subject had 2 comparable 
wound areas identified, excised to remove nonviable tissue, and randomized to receive 
StrataGraft skin tissue or an autograft.  Thirty subjects were enrolled in this dose escalation 
study.  Subjects in Cohort 1 received up to 220 cm2 of StrataGraft skin tissue while those in 
Cohort 2 received up to 440 cm2 of StrataGraft skin tissue.  Cohort 3 was completed as a clinical 
comparability evaluation of StrataGraft skin tissue that had been cryopreserved and stored 
frozen.  Subjects in Cohort 3 received up to 440 cm2 of thawed StrataGraft skin tissue.  None of 
the sites treated with StrataGraft skin tissue required autografting by Day 28.  Additionally, 27 
of the 28 per-protocol subjects had wound closure of treatment sites at the 3 month study 
session.  No safety signal was seen following application of StrataGraft skin tissue.  Molecular 
analysis of patient biopsy samples found no evidence of deoxyribonucleic acid (DNA) from cells 
of StrataGraft skin tissue after 3 months, indicating that StrataGraft skin tissue had not 
engrafted but was replaced by the patient’s own skin. 
The STRATA2001 and STRATA2011 studies provided several important clinical findings that 
informed the development of this Phase III STRATA2016 protocol: 
None of the complex skin defects containing intact dermal elements treated with
StrataGraft skin tissue required autografting of these areas by Day 28.  These results
exceeded the metrics agreed to prior to the study that a 50% reduction in the
StrataGraft-treated area requiring autografting is clinically meaningful.
The absence of donor site harvest required for areas treated with StrataGraft skin tissue
resulted in significantly less pain, fewer sequelae, and superior cosmesis relative to the
autograft donor site.

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 StrataGraft skin tissue did not permanently engraft and was replaced by the patient’s 
own cells by 3 months. 
 StrataGraft skin tissue remained intact, adherent, and viable in full-thickness skin 
defects for at least 7 days, during which time it likely acted as a continuous source of 
factors that are anticipated to promote autologous skin tissue regeneration. 
 
The STRATA2016 Phase III study builds upon data generated by the STRATA2001 and 
STRATA2011 studies.  This registration study is designed as 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.  Targeted 
enrollment for the study is approximately 70 subjects who have thermal burns of 3 to 49% 
TBSA, including an area that contains intact dermal elements for which surgical excision and 
autografting are clinically indicated. 
 
After surgical excision of nonviable tissue, 2 comparable areas of comparable depth on each 
subject will be identified and the areas will be randomized to receive StrataGraft skin tissue or a 
surgically harvested autograft.  The intrapatient comparator allows for a matched control to 
eliminate significant underlying differences including immunologic, physiologic, and scarring 
variables inherent in this patient population that affect the healing trajectories of the burn.  
Two donor sites will be prospectively identified to provide sources of autografts for the control 
and StrataGraft treatment sites as needed.  After surgical excision of nonviable tissue, the 
StrataGraft tissue and autograft will be placed on the treatment sites in accordance with the 
randomization. 
 
Efficacy will be assessed by 1) evaluating the difference in the percent area of the StrataGraft-
treated and autograft-treated sites that are autografted by 3 months and 2) evaluating the 
proportion of subjects achieving durable wound closure of the StrataGraft treatment site at 
3 months without autograft placement.  The pain of the donor sites will be assessed through 
Day 28, donor site sequelae will be assessed at each study session after treatment Day 0, and 
cosmesis of the treatment sites and donor sites will be evaluated at 3, 4, 6, and 12 months.  
Incidence of wound closure and percent wound closure will be assessed at Day 28, as well as 
2, 3, 4, 6 and 12 months.  Additional assessments include subject and physician satisfaction with 
the StrataGraft treatment site, duration of hospitalization due to donor site pain, presence of 
allogeneic DNA at 3 months, and need for scar manipulation therapy of the treatment sites for 
tissue normalization.  Safety assessments include monitoring of treatment-emergent AEs, vital 
signs, safety laboratory parameters, incidence of wound infection, donor site complications, 
histologic wound bed analysis, immunologic responses to StrataGraft skin tissue, as well as 
concomitant medications and procedures. 
 
 
 
 
 

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Application of up to 440 cm2 of StrataGraft skin tissue in the STRATA2011 trial was shown to be 
well tolerated with no evidence of safety concerns when applied to complex skin defects due to 
thermal burns that contained intact dermal elements.  All subjects in the STRATA2016 study will 
receive a single application of up to 1,000 cm2 StrataGraft skin tissue following surgical excision 
of nonviable tissue.  The preidentified treatment sites must each be a single, contiguous wound 
area of comparable depth but the StrataGraft treatment site and control treatment sites may 
be non-contiguous to each other.  The StrataGraft treatment site may be up to 2 times the area 
of the autografted comparator site.  StrataGraft skin tissue will be left in place after topical 
application.  Routine safety monitoring will be performed by the study’s medical monitor (MM) 
and the Data and Safety Monitoring Board (DSMB). 
 
Co-Primary Clinical Efficacy Endpoints 
1. The difference in the percent area of the StrataGraft treatment site and control autograft 
treatment site that is autografted by 3 months. 
2. The proportion of subjects achieving durable wound closure of the StrataGraft treatment 
site at 3 months without autograft placement. 
 
Ranked Secondary Efficacy Endpoints 
The difference between the StrataGraft and autograft donor sites in the average pain intensity 
through Day 14 based on the Wong-Baker FACES pain rating scale (FPRS). 
The difference between the StrataGraft and autograft donor site cosmesis at 3 months based on 
observer Patient and Observer Scar Assessment Scale (POSAS) total score. 
The difference between the StrataGraft and autograft treatment site cosmesis at 12 months based 
on observer POSAS total score. 
 
Mechanism Endpoint 
The proportion of the StrataGraft treatment sites that test positive for residual DNA from the 
cells of the StrataGraft skin tissue at 3 months. 
 
Exploratory Efficacy Endpoints 
 
 
 
 
 
 

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Statistical Methods 
The data will be summarized with descriptive statistics by treatment group, and the specific 
statistical tests comparing the treatments will be documented in the Statistical Analysis Plan.  
SAS version 9.4 or newer will be used. 
 
Efficacy Assessments  
Assessments 
Methods 
Schedule of Assessments 
Percent area of the 
treatment sites autografted. 
Clinician assessment supported 
by photodocumentation. 
Days 3, 7, 14, 28 as well as 2, 3, 4, 
and 6 months. 
 
  
 
 
 
 
Pain of donor sites. 
FPRS. 
Days 3, 7, 14 and 28. 
Cosmesis of donor sites. 
POSAS supported by 
photodocumentation. 
3, 4, 6 and 12 months. 
 
 
 
 
 
 
 
 
Cosmesis of treatment sites. 
POSAS supported by 
photodocumentation. 
3, 4, 6 and 12 months. 
Presence of allogeneic DNA. 
PCR of short tandem repeats. 
Baseline and 3 months. 
 
 
 
 
 
 
 
 
 
 
 

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Safety Assessments  
Assessments 
Methods 
Schedule of Assessments 
Adverse events, including 
treatment-emergent 
adverse events. 
Standard. 
Throughout study duration. 
Vital signs. 
Blood pressure, temperature, and 
pulse. 
Every study session. 
Incidence of infection. 
Clinical signs and symptoms; laboratory 
evidence as needed. 
Every study session. 
Concomitant 
medications. 
Standard. 
Every study session. 
Concomitant procedures. 
Standard. 
Every study session. 
Safety laboratory values.  
Comprehensive metabolic panel (CMP) 
& complete blood count (CBC) with 
differential. 
Baseline and Days 7 and 28. 
Immunological 
evaluations. 
Panel reactive antibodies (PRA). 
Baseline, 28 days, and 3 
months. 
Anti-bovine serum albumin (BSA) 
antibodies. 
Baseline and 3 months. 
Histologic wound bed 
analysis 
For cellular integrity and tissue 
architecture. 
Study Session #1. 
Donor site complications. 
Clinician assessment. 
Days 3, 7, 14, 28 as well as 2, 3, 
4, 6 and 12 months. 
 
 
 
 
 
 
INCLUSION CRITERIA 
Subject-specific criteria 
Treatment site-specific criteria 
 Men and women aged ≥ 18 years. 
 Written informed consent. 
 Sufficient healthy skin identified and 
designated as a donor site in the event that 
the StrataGraft treatment site requires 
autografting. 
 Clinical expectation that study donor site 
will heal without grafting. 
 Complex skin defects of 3 to 49% TBSA. 
 Total burn may consist of more than 
one area.  
 Thermal burn(s) with 
intact dermal elements for 
which excision and 
autografts are clinically 
indicated. 
 Total of both study 
treatment areas can be up 
to 2000 cm2. 
 First excision and grafting 
of study treatment sites. 
 Thermal burn(s) on the 
torso, and upper or lower 
extremities. 
 

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EXCLUSION CRITERIA 
Subject-specific criteria 
Treatment site-specific criteria 
 Pregnant women. 
 Prisoners. 
 Subjects receiving systemic 
immunosuppressive therapy. 
 Subjects with a known history of 
malignancy. 
 Preadmission insulin-dependent diabetic 
subjects. 
 Subjects with concurrent conditions that in 
the opinion of the investigator may 
compromise subject safety or study 
objectives. 
 Expected survival of less than 3 months. 
 Participation in the treatment group of an 
interventional study within 90 days prior to 
enrollment. 
 Full-thickness burns. 
 Chronic wounds. 
 The face, head, neck, 
hands, feet, buttocks, and 
areas over joints. 
 Treatment sites 
immediately adjacent to 
unexcised eschar. 
 Clinical or laboratory 
determination of infection 
at the anticipated treatment 
sites. 
 
NUMBER OF SUBJECTS 
Targeted enrollment for this study is approximately 70 study subjects who have complex skin 
defects due to thermal burns that contain intact dermal elements and for which excision and 
autografts are clinically indicated. 
 
ESTIMATED DURATION OF CLINICAL STUDY 
Open Enrollment Period 
24 months 
Planned Subject Contact Duration 
12 months 
 
Screening Period (Within 7 Days Prior to Treatment) 
Subjects with complex skin defects containing intact dermal elements who after surgical 
excision of an area of thermal burn meet all eligibility criteria would qualify for this study. 
 
TEST PRODUCT 
StrataGraft skin tissue contains an epidermal layer comprising differentiated, multilayered, 
epidermal keratinocytes from a single human donor grown on a collagen matrix embedded with 
fibroblasts from a second human donor.  StrataGraft skin tissue is not a patient-specific product 
but an allogeneic human skin substitute.  StrataGraft skin tissue is produced from well-
characterized cell banks of pathogen-free human keratinocytes and fibroblasts.  StrataGraft skin 
tissue reproduces many of the structural and biological properties of normal human skin and is 
intended to provide immediate wound coverage, barrier function, and sustained expression of 
wound healing factors to promote the healing of complex skin defects. 

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TEST PRODUCT ROUTE OF ADMINISTRATION AND DOSE REGIMEN 
Following excision of nonviable tissue, 2 treatment sites that contain intact dermal elements 
and are up to 1,000 cm2 each on the upper or lower extremities or torso will be prospectively 
identified.  The treatment sites should be of comparable depth and have similar potentials for 
experiencing mechanical shear forces post-grafting.  Prior to randomization, the 2 identified 
treatment sites must be labeled as sites A and B.  Treatment site A will always be anterior, 
superior/proximal, lateral or to the subject’s right.  Treatment site B will always be posterior, 
inferior/distal, medial or to the subject’s left.  After identification, the sites will be randomized 
to receive up to 1,000 cm2 StrataGraft skin tissue or up to 1,000 cm2 autologous skin graft.  
Though sites A and B need not be contiguous to each other, each individual treatment site must 
be a single, contiguous area.  The StrataGraft treatment site may be the same size as or up to 
twice the area of the autograft control site.  Any remaining wound outside the identified study 
treatment sites will be treated according to the institutional SOC for that type of wound. 
 
REGULATORY INFORMATION AND QUALITY STATEMENT 
The study will be conducted under an active investigational new drug application (IND) which 
has been prepared and submitted to the Center for Biologics Evaluation and Research (CBER), 
United States Food and Drug Administration (FDA) to support the evaluation of safety and 
efficacy of StrataGraft skin tissue in the management of complex skin defects. 
 
This study will be conducted in compliance with applicable regulation and guidance related to 
Good Clinical Practice (GCP) and in compliance with this protocol.