Open-label, Controlled, Randomized, Multicenter, Dose Escalation Study Evaluating the Safety, Tolerability, and Efficacy of Single or Multiple Applications of StrataGraft® Skin Tissue as an Alternative to Autografting Full-thickness Complex Skin Defects
Phase: PHASE2
Conditions: Trauma-related Wound, Burns, Skin Wound
Sponsor: Stratatech, a Mallinckrodt Company

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 1 of 56 
  
 
 
 
AN OPEN-LABEL, CONTROLLED, RANDOMIZED, MULTICENTER, DOSE 
ESCALATION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND EFFICACY 
OF SINGLE OR MULTIPLE APPLICATIONS OF STRATAGRAFT® SKIN TISSUE AS AN 
ALTERNATIVE TO AUTOGRAFTING FULL-THICKNESS COMPLEX SKIN DEFECTS  
 
 
 
 
STRATA2014 
PHASE II CLINICAL PROTOCOL 
 
 
 
Version 3 
March 23, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document is a confidential communication of Stratatech Corporation.  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document constitutes the agreement by the recipient that no unpublished information contained 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 

Stratatech@ Corporation, a Mallinckrodt Company - Confidential
STRATA20 14 Clinical Study Protocol
Page 2 of 56
Corporation, except that this document may be disclosed to appropriate institutional review
boards/ethical committees so long as they are requested to maintain its confidentiality.
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
Investigator Statement (FORM FDA-1572), the Clinical Investigators agree to abide by US
federal regulations and the study protocol during the course of the clinical trial conducted under
an IND application.
SPONSOR:
STRATATECH CORPORATION,
a Mallinckrodt Company
510 Charmany Drive
Suite 150
Madison, WI 53719
Approved by:
tatez A3lryqe?tlfl
Vice President of Regenerative Medicine

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 3 of 56 
LIST OF ABBREVIATIONS/DEFINITIONS 
 
AE 
Adverse event 
ALT 
Alanine transaminase/SGPT 
Allograft 
Transplant from one person to another person 
AST 
Aspartate transaminase/SGOT 
Autograft 
Transplant from one anatomical location to another within the same person 
BSA 
Bovine serum albumin 
BSE 
Bovine spongiform encephalopathy 
CBC 
Complete blood count 
CBER 
Center for Biologics Evaluation and Research 
CFR 
Code of Federal Regulations 
CMP 
Comprehensive metabolic panel 
CRF 
Case report form 
CRO 
DoD 
Contract research organization 
Department of Defense 
DSMB 
Data and safety monitoring board  
FDA 
Food and Drug Administration 
FPRS 
Wong-Baker FACES pain rating scale  
GCP 
Good clinical practice 
HgB 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act 
HRPO 
Human Research Protection Office 
IB 
Investigator’s brochure  
ICH 
International Conference on Harmonisation 
IND 
Investigational new drug 
IRB 
Institutional review board 
MHC  
Major histocompatibility complex  
MM  
Medical monitor 
NIKS® 
Near-diploid human keratinocytes 
ORP 
Office of Research Protections 
PHI 
Protected health information 
POSAS 
Patient and observer scar assessment scale 
PRA 
Panel reactive antibodies 
QA 
Quality assurance 
QC 
Quality control 
SAE 
Serious adverse event 
SD 
Standard deviation 
SOC 
Standard of care 
TBSA 
UPIRTSO 
Total body surface area 
Unanticipated problem involving risks to subjects or others 
USAMRMC 
U. S. Army Medical Research and Materiel Command 
WBC 
White blood cells 
 
 
 
 
 
 
 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 4 of 56 
SUMMARY OF STRATA2014 PROTOCOL 
TITLE OF STUDY 
Open-label, controlled, randomized, multicenter, dose escalation study evaluating the safety, 
tolerability, and efficacy of single or multiple applications of StrataGraft® skin tissue as an 
alternative to autografting full-thickness complex skin defects  
 
CLINICAL PHASE 
Phase II 
 
STUDY OBJECTIVE 
The objective of this study is to assess the safety, tolerability, and efficacy of increasing dosages 
of a single or multiple applications of StrataGraft skin tissue in the treatment of full-thickness 
complex skin defects on the arms, legs, and torso. 
 
STUDY RATIONALE  
The current standard of care (SOC) for severe burns and other complex skin defects is surgical 
harvesting of a sheet of healthy skin from an uninjured site on the patient and transplantation of 
this autologous skin graft to the wound after excision of non-viable tissue.  While this process can 
be effective in providing closure of the original wound, it has significant limitations related to the 
iatrogenic donor site wounds created during surgical removal of autologous skin tissue.  These 
donor site wounds are extremely painful, prone to infection and scarring, and can themselves 
convert to full-thickness wounds that must then be managed to promote healing.  In addition, the 
amount of healthy skin available for harvesting is frequently limited in large burns, necessitating 
sequential re-harvesting of available donor sites.  As a result, there is an urgent need for alternatives 
to donor site harvesting for treatment of severe burns and other complex skin defects.  
 
This range-finding study is designed to evaluate StrataGraft skin tissue as an alternative to 
autografting in promoting autologous tissue regeneration of the full-thickness component of 
complex skin defects resulting from acute traumatic skin loss (e.g., burn or degloving injuries).  
StrataGraft skin tissue is an off-the-shelf, biologically active human skin substitute which is 
anticipated to provide immediate wound coverage and aid in wound bed conditioning and tissue 
regeneration.  Based on over 25 years of clinical experience with human skin substitutes containing 
living allogeneic cells,1 as well as prior clinical experience with StrataGraft skin tissue, 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.   
 
Stratatech has completed STRATA2001, a first-in-human, dose escalation trial evaluating the 
safety of StrataGraft skin tissue in subjects with complex skin defects of 5-73% total body surface 
area (TBSA) resulting from thermal injury, trauma, or necrotizing fasciitis.  This study showed 
that autograft take in wound beds temporized with StrataGraft skin tissue was comparable to 
autograft take in wounds temporized with cadaver allograft.  No product-related adverse events 
(AE) were seen following application of StrataGraft skin tissue to the full-thickness component of 
these complex skin defects for seven days.  There was no change in the types of AE as the total 
                                                 
1 Rennert RC, Rodrigues M, Wong VW, et al. Biological therapies for the treatment of cutaneous wounds: phase III 
and launched therapies. Expert Opin Biol Ther. 2013;13(11):1523-1541. 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 5 of 56 
dosage of StrataGraft skin tissue increased 5-fold across the three cohorts from 44 cm2 to 220 cm2.  
StrataGraft skin tissue remained intact and viable throughout the seven day placement period, 
suggesting the potential for continued biological activity during longer exposure. 
 
The STRATA2011 study, a follow-up to the STRATA2001 trial, has been conducted as an open-
label, dose-escalation, multicenter study evaluating the safety, tolerability, and efficacy of 
prolonged exposure to increasing dosages of a single application of StrataGraft skin tissue in 
promoting the healing of complex skin defects with intact dermal elements.  In STRATA2011, a 
single application of StrataGraft tissue was applied to the deep partial-thickness portion of thermal 
burns and left in place to evaluate whether StrataGraft could promote autologous tissue 
regeneration thereby reducing or eliminating the need for the surgical harvesting of a donor site 
for autografting.   
 
The STRATA2011 study included subjects with complex skin defects whose total injury areas 
range from 3-43% TBSA due to thermal injury.  Each subject had two comparable wound areas 
containing intact dermal elements that were identified and randomized to receive StrataGraft or an 
autologous skin graft.  Thirty subjects were enrolled in this dose escalation study and those in 
cohort 1 received up to 220 cm2 while those in cohorts 2 and 3 received up to 440 cm2 of 
StrataGraft skin tissue.  None of the study sites treated with StrataGraft skin tissue required 
autografting by day 28 (primary efficacy endpoint).  No safety signal was seen following 
application of StrataGraft skin tissue, and 27 of the 28 per-protocol subjects had complete wound 
closure of treatment sites at the 3 month study session (primary safety endpoint).  The presence of 
DNA from StrataGraft tissue was assessed after three months to evaluate whether StrataGraft 
tissue had permanently engrafted.  Molecular analysis of patient biopsy samples found no evidence 
of DNA from cells of StrataGraft tissue.   
 
The STRATA2001 and STRATA2011 studies provided several important clinical findings that 
have informed the development of this phase II STRATA2014 protocol: 
 StrataGraft remains intact, adherent, and viable in complex skin defects for at least seven 
days, during which time it is anticipated to act as a continuous source of factors that are 
involved in promotion of autologous tissue regeneration. 
 StrataGraft tissue does not permanently engraft and is replaced by the patient’s own cells 
by three months. 
 None of the complex skin defects containing intact dermal elements treated with 
StrataGraft tissue required autografting by day 28 eliminating the need for autografting. 
These results exceeded the expectations established prior to the study that a 50% reduction 
in the StrataGraft-treated area that ultimately requires autografting would be clinically 
meaningful. 
 The absence of donor site harvest for areas treated with StrataGraft tissue resulted in 
significantly less pain and other morbidities as well as improved cosmesis associated with 
the prospective donor site wounds. 
      
The STRATA2014 study builds upon the data generated in the STRATA2001 and STRATA2011 
studies in the same patient population as that for STRATA2001.  The proposed study is designed 
as an open-label, controlled, randomized, multicenter, dose-escalation study evaluating the safety, 
tolerability, and efficacy of single or multiple applications of StrataGraft skin tissue as an 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 6 of 56 
alternative to donor site harvesting and autografting in promoting the healing of full-thickness 
complex skin defects.  The proposed study population will include subjects with up to 49% TBSA 
complex skin defects including a full-thickness component.  Targeted enrollment for this study is 
up to 20 subjects with full-thickness complex skin defects requiring surgical excision and 
autografting.  Subjects will be sequentially enrolled in two cohorts of increasing dosage of 
StrataGraft skin tissue (treatment area per surgical application).  Subjects will be eligible to receive 
up to three applications of StrataGraft skin tissue in the treatment of full-thickness skin defects.  In 
the first cohort, up to 10 subjects will receive an initial surgical application of up to 200 cm2 of 
StrataGraft skin tissue.  The second cohort will enroll up to 10 subjects who will receive an initial 
treatment of up to 400 cm2 of StrataGraft skin tissue.  The treatment site will be evaluated to assess 
the progress of wound healing.  Per the clinical judgment of the Clinical Investigator and as 
necessary to promote complete wound closure, wounds may be treated with up to two additional 
applications StrataGraft tissue.  The cumulative study dosage for cohort 1 may be up to 600 cm2 
and for cohort 2 may be up to 1200 cm2. 
 
Two comparable wounds in each subject will be identified and the wounds randomized to receive 
StrataGraft skin tissue or a surgically harvested autologous skin graft.  The intrapatient comparator 
design allows for a matched control to eliminate significant underlying immunologic, physiologic, 
and scarring variables inherent in this population.  Two donor sites will be prospectively 
designated to provide a source of autograft skin for the control treatment site and, if needed, the 
StrataGraft treatment site.  Both the StrataGraft skin tissue and autograft control will be placed on 
the treatment sites immediately following surgical excision of non-viable tissue.  After the fifth 
subject in cohort 1 reaches the three month study session, an interim safety report will be generated 
and reviewed by the Data and Safety Monitoring Board (DSMB).  Progression to cohort 2 will 
take place only after a favorable review of the safety information by the DSMB.   
 
Efficacy will be assessed by evaluating the percent area of the StrataGraft treatment site requiring 
autografting by 3 months, pain of the donor sites through day 28, and the incidence of complete 
wound closure at three months supported by clinical photography.  Cosmesis of the treatment sites 
will be evaluated at 3, 6, and 12 months.  Additional assessments will include persistence of 
allogeneic DNA in the StrataGraft-treated sites as well as cosmesis and pain of the donor sites.  
Safety assessments will include monitoring of AE, vital signs, laboratory safety values, incidence 
of wound infection, and immunologic responses to StrataGraft tissue.   
 
In addition to routine safety monitoring by the study’s medical monitor (MM) and the DSMB, the 
study will have a Department of Defense (DoD) research monitor whose sole responsibility will 
be to assess safety.  The decision to advance to cohort 2 will be based on an interim safety analysis 
by the DSMB after the fifth subject in the first cohort has completed the 3 month visit.  This time 
frame will allow for the evaluation of acute, sub-acute, and early chronic AE resulting from 
prolonged exposure and multiple applications of StrataGraft skin tissue in these subjects.  
Enrollment into the second cohort will begin only after the DSMB has reviewed the interim safety 
data and recommended progression. A copy of the interim analysis will also be submitted to the 
Investigational New Drug (IND) on file for StrataGraft skin tissue.   
 
STUDY DESIGN 
Primary clinical endpoints 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 7 of 56 
 Percent area of the StrataGraft treatment site requiring autografting by 3 months  
 Wound closure of the treatment sites at 3 months 
 
Secondary clinical efficacy assessments 
 Percent of subjects requiring autografting of the StrataGraft treatment site by 3 months 
 Incidence of complete wound closure of the treatment sites at 3, 6, and 12 months 
 Percent wound closure at 3, 6, and 12 months 
 Cosmesis of treatment sites at 3, 6, and 12 months  
 Cosmesis of donor sites at 3, 6, and 12 months  
 Pain of donor sites measured at days 3, 7, 14, 21, and 28  
 
Secondary clinical safety assessments 
 Treatment-emergent AE assessed throughout study duration 
 Incidence of infection assessed at all study sessions 
 Vital signs assessed at all study sessions 
 Safety laboratory values at baseline, day 7, and day 28 
 Immunology assessments at baseline, day 28, and 3 months 
 Archival plasma and leukocyte collection at baseline and 3 months 
 Persistence of allogeneic DNA at 3 months  
 
Statistical methods 
 Standard statistical measures 
 SAS statistical program 
 
Study Assessments (efficacy) 
 
Assessments 
Methods
Schedule of Assessments
Percent area of treatment site 
requiring autografting 
Clinician assessment supported 
by photodocumentation 
Days 3, 7, 14, 21, 28 and 3 
months 
Wound closure of treatment 
sites  
Clinician assessment supported 
by  photodocumentation
3, 6, and 12 months 
Cosmesis of treatment sites 
POSAS supported by 
photodocumentation
3, 6, and 12 months 
Cosmesis of donor sites  
POSAS supported by 
photodocumentation
3, 6, and 12 months 
Pain of donor sites  
Wong-Baker FACES pain rating 
scale (FPRS)
Days 3, 7, 14, 21, and 28 
 
 
 
 
Study Assessments (safety) 
Assessments 
Methods
Schedule of Assessments
Blood chemistry and safety 
laboratory parameters  
CMP and CBC with differential
Baseline, 7 and 28 days and as 
per SOC 
Vital signs 
Blood pressure, temperature and 
pulse
Every study session 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 8 of 56 
Immunological evaluations 
Panel reactive antibodies (PRA)
Baseline, 28 days, and 3 months
Anti-bovine serum albumin 
(BSA) antibodies  
Baseline and 3 months 
Incidence of infection 
Clinical signs and symptoms; 
laboratory evidence as necessary
Every study session 
Presence of allogeneic DNA  
PCR of short tandem repeats 
Baseline and 3 months 
Adverse events 
Standard
Throughout study duration
 
NUMBER OF SUBJECTS 
Targeted enrollment for this study is up to 20 study subjects who have full-thickness complex skin 
defects.   
 
ESTIMATED DURATION OF CLINICAL STUDY 
Open Enrollment Period 
18 months
Planned Subject Conduct Duration 
12 months
 
Screening period (up to 7 days prior to treatment) 
Subjects with full-thickness complex skin defects who meet all inclusion and exclusion criteria 
would qualify for this study. 
 
INCLUSION CRITERIA 
Subject-specific criteria 
Study site-specific criteria 
 
Men and women aged 18-65 years, inclusive 
 
Written informed consent  
 
Sufficient healthy skin identified and reserved as a 
donor site in the event that the StrataGraft treatment 
site requires autografting  
 
Complex skin defects of up to 49% TBSA requiring 
excision and autografting  
o Total skin defect may consist of more than one 
wound area  
 
Full-thickness complex skin defect(s) requiring 
excision and autografting 
 
Study treatment sites on the torso and limbs may 
be up to 200 cm2 in cohort 1 and 400 cm2 in cohort 
2 
 
For thermal burns only, first excision and grafting 
of treatment sites  
 
 
 
 
 
 
 
 
 
 
EXCLUSION CRITERIA 
Subject-specific criteria 
Study site-specific criteria 
 
Pregnant women and prisoners  
 
Subjects receiving systemic immunosuppressive 
therapy  
 
Subjects with a known history of malignancy  
 
Chronic wounds  
 
The face, head, neck, hands, feet, buttocks, 
perineum, and area over joints  

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 9 of 56 
 
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 < 3 months  
 
Participation in the treatment group of an 
interventional study within the 90 days prior to 
enrollment 
 
Treatment sites with exposed tendon or bony 
prominences 
 
Chemical and electrical burns  
 
Treatment sites directly adjacent to unexcised 
eschar  
 
Clinical determination of infection at the 
anticipated treatment sites 
 
TEST PRODUCT 
StrataGraft skin tissue contains an epidermal layer comprised of 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 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.  
  
TEST PRODUCT ROUTE OF ADMINISTRATION AND DOSE REGIMEN 
Two full-thickness wound areas of comparable depth and area (contiguous or non-contiguous with 
each other) on the arms, legs, or torso in subjects with complex skin defects will be prospectively 
identified as treatment 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 excision, the two sites will be randomized to be treated with 
StrataGraft skin tissue or autograft.  Each treatment site must be a single contiguous full-thickness 
wound area.  Any wound outside the study treatment sites will be treated according to the 
institutional standard of care for that wound.   
 
Subjects in cohort 1 may receive an initial dosage of up to 200 cm2 each of StrataGraft skin tissue 
and autograft.  Subjects in cohort 2 may receive an initial dosage of up to 400 cm2 each of 
StrataGraft skin tissue and autograft.  StrataGraft skin tissue is to be meshed 1:1 prior to 
application.  Autograft may be meshed up to 4:1 as per SOC prior to application. 
 
Subjects in both cohorts are eligible to receive up to two additional applications of StrataGraft skin 
tissue days 6 through 31, inclusive at the discretion of the Clinical Investigator as deemed clinically 
necessary to promote complete wound closure.  The subsequent applications of StrataGraft tissue 
will be applied to wounds after surgical or non-surgical debridement of the wound areas consistent 
with standard practice.   
 
 
REGULATORY INFORMATION AND QUALITY STATEMENT 
This study will be conducted under an active IND application 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.   
 

Stratatech® Corporation, a Mallinckrodt Company - Confidential  
STRATA2014 Clinical Study Protocol 
Page 10 of 56 
This study will be conducted in compliance with applicable regulation and guidance related to 
Good Clinical Practice (GCP).