A Prospective Multicenter Randomized Controlled Clinical Study to Investigate the Safety and Effectiveness of RES (Regenerative Epidermal Suspension) Prepared With the RECELL® Device Compared to Conventional Care for Healing of Donor Sites in Infants, Children and Adolescents (Aged 1-16 Years)
Phase: NA
Conditions: Skin; Deformity
Sponsor: Avita Medical

 
 
 
 
 
 
 
A Prospective Multicenter Randomized Controlled Clinical Study to Investigate the 
Safety and Effectiveness of RES (Regenerative Epidermal Suspension) Prepared 
with the RECELL® Device Compared to Conventional Care for Healing of Donor 
Sites in Infants, Children and Adolescents (Aged 1–16 Years)  
 
 
 
Investigational Plan 
 
Study Number:  
 
CTP006-1 
Device:  
 
 
RECELL Autologous Cell Harvesting Device 
Study Type: 
 
Pivotal Study 
IDE Reference Number: 
13053 
Issue Date/Version:  
October 30, 2018 / Revision 3 
Sponsor:  
 
 
AVITA Medical Americas, LLC 
28159 Avenue Stanford, Suite 220 
Valencia, CA 91355 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR’S STATEMENT 
This statement is to certify that I have received the above-referenced investigational plan, which has 
been approved for initiation at my investigational site by the Institutional Review Board on the date of 
____________.  As Principal Investigator, I will ensure that all personnel who have been delegated 
responsibilities for this study will be trained on the investigational plan and associated responsibilities 
prior to study participation.  I agree to conduct this clinical study in compliance with the investigational 
plan and applicable requirements of the U.S. Code of Federal Regulations (21 CFR Parts, 50, 54, 56, 
812 and 45 CFR Part 46). 
 
Signature: ____________________________________ 
Date: _______________ 
 
                 Principal Investigator                   
 
 

 
 
PROTOCOL SYNOPSIS 
Title 
A Prospective Multicenter Randomized Controlled Clinical Study to Investigate the Safety 
and Effectiveness of RES (Regenerative Epidermal Suspension) Prepared with the 
RECELL® Device Compared to Conventional Care for Healing of Donor Sites in Infants, 
Children and Adolescents Aged 1–16 Years  
Protocol No. 
CTP006-1 
Sponsor 
AVITA Medical Americas, LLC 
28159 Avenue Stanford, Suite 220 
Valencia, CA 91355 
Funding 
Funded by the Biomedical Advanced Research and Development Authority (BARDA) 
within the Office of the Assistant Secretary for Preparedness and Response in the U.S. 
Department of Health and Human Services 
Investigational Donor 
Site Treatment 
Application of RES prepared using the RECELL® Autologous Cell Harvesting Device + 
Telfa™ Clear primary and Xeroform™ secondary wound dressings 
Control Donor Site 
Treatment 
Telfa™ Clear primary and Xeroform™ secondary wound dressings 
Phase of Study 
Pivotal Study 
Proposed Indication 
The RECELL Device is indicated for use to aid healing of split-thickness donor sites 
created in treatment of complex skin defects requiring autografting in patients 1 year of 
age or greater. 
Primary Objectives 
To evaluate whether time to complete closure is superior for RECELL-treated split-
thickness donor sites, compared with Control (standardized dressings only).  The mean 
time to donor site healing will be compared between treatments.  
Planned Enrollment 
Randomized Accrual: It is anticipated that a minimum of 50 randomized subjects will be 
enrolled in the study to evaluate the primary endpoint and to gain additional RECELL 
device experience for the proposed indication.  
 
Roll-In, Non-Randomized Accrual: Additionally, up to 2 roll-in subjects may be treated 
with the RECELL device at each of up to 5 investigational sites prior to commencement 
of randomization at that site to assure proficiency with the investigational device and study 
procedures. Thus, up to 10 roll-in subjects may be enrolled in addition to the randomized 
subjects. All roll-in subjects must meet the same eligibility criteria and will undergo the 
same follow-up assessment as the randomized subjects; however, data from this cohort of 
subjects will be analyzed separately from the randomized cohort. 
 
Therefore, the total planned subject accrual within this study including both the non-
randomized and randomized cohorts is anticipated to be a minimum of 60 subjects.  
 
This study utilizes an adaptive design with sample size re-estimation. The maximum 
enrollment in the randomized phase will be set to 100 subjects, thus the total maximum 
enrollment in the study with inclusion of the non-randomized cohort will be 110 subjects. 
Trial Design 
This is a prospective, within-subject, paired, randomized (1:1), blinded evaluator, 
multicenter trial to investigate whether application of RES can be safely and effectively 
used to promote wound healing of donor sites created when harvesting skin for 
autografting. Additionally, the impact of the use of RECELL will be investigated with 
respect to pain, itching, subject and investigator treatment preference and donor site scar 
outcomes, and RECELL device safety. 
 
Infants, children and adolescents aged from 1 through 16 years, both males and females, 
with complex skin defects over a total body surface area (TBSA) of between 5% and 25% 
(inclusive) which require autografting will be considered for participation in this study. 
Subject consent, and assent (as applicable), will be obtained prior to conduct of any study-
related procedures. This study utilizes a matched pairs design, where each subject will 
have two designated donor sites of similar surface area (representing a minimum of 1% 

 
 
TBSA each) randomized to receive treatment with RECELL or control dressing. The 
primary and secondary dressing for each study donor site (RECELL and Control) should 
be distinct, without any overlap. 
 
In addition to the study donor sites, other areas (partial-thickness defects, meshed 
autografts and non-study donor sites) may have RES applied at the discretion of the 
investigator. Only the randomized donor sites (designated study donor sites) will be part 
of the study area for evaluation of all endpoints.  Subjects and their parent/guardian will 
be blinded to treatment assignment.  
 
Subjects should be seen 2 days post-treatment for secondary dressing changes, as clinically 
indicated. Follow-up visits will be scheduled Monday, Wednesday and Friday until 
complete healing is confirmed. The first follow-up visit will be on Friday for subjects who 
are treated Monday or Tuesday, on Monday for subjects treated Wednesday, Thursday or 
Friday, and on Wednesday for subjects who are treated Saturday or Sunday. Study donor 
sites will also be evaluated at Week 4. Longer-term follow-up visits will be performed at 
Weeks 8, 16, 24, 36 and 52.  
 
Study donor site healing will be evaluated via direct visualization by the treating 
investigator (non-blinded investigator) and by a qualified clinical investigator blinded to 
treatment allocation (i.e., Blinded Evaluator). The blinded assessment will serve as the 
primary healing assessment. During the early assessments, pain, itching, and subject and 
investigator treatment preference will be documented. Study donor sites will be 
documented using digital photography. At longer term visits, study donor site scar 
outcomes will be rated using the Patient and Observer Scar Assessment Scale (POSAS) 
questionnaire which includes components for both the Blinded Evaluator and the subject 
(or parent/guardian as appropriate). 
 
A sample size re-estimation will be conducted after approximately 50% of total 
randomized enrollment has completed the primary effectiveness endpoint (i.e., 25 subjects 
have reached the healing endpoint) and the sample size adjusted upwards as necessary.  
Number of Trial 
Centers 
It is planned that eight (8) US trial centers with a specialty in pediatric burn/injury care 
will participate. No site will contribute more than 30% of the total randomized subjects 
without written Sponsor permission. 
Duration of 
Participation 
Each subject will participate in the trial for 52 weeks post-treatment. 
 
Primary Effectiveness 
Endpoint 
The primary effectiveness endpoint is time (in days) to complete closure of study donor 
sites confirmed at two consecutive visits. It is anticipated that time to complete closure 
will be superior for application of RES on donor sites compared to conventional treatment 
(Control). 
 
Wound closure will be defined as complete when ≥95% epithelialization has been 
achieved as assessed by the blinded evaluator. This definition for donor site healing (i.e., 
complete closure), is consistent with FDA guidance1 and consensus standards established 
by the American Burn Association (ABA)2. 
Safety Endpoints 
All treatment-related adverse events will be documented. 
 
Safety variables compared between the two treatments are: incidence of donor site specific 
adverse events including but not limited to infection, allergic reaction, delayed healing, 
pain, and scars requiring intervention. 
 
 
 
1 Guidance for Industry: Chronic Cutaneous Ulcer and Burn Wounds – Developing Products for Treatment (June 2006). 
2 Singer, Adam J., et al. "Burn Wound Healing Outcomes." Journal of Burn Care & Research 34.4 (2013): 381-385. 

 
 
Secondary Effectiveness 
Endpoints 
The following secondary endpoints will be evaluated for superiority of RECELL over 
Control: 
1. Donor Site Treatment Preference at Week 4 (reported by subjects 8 years of age 
or older, or by parent/guardian if subject is less than 8 years of age). 
2. Investigator Donor Site Treatment Preference at Week 4. 
3. Comparative Itching of study donor sites during 1st week post-treatment (Day 7 
± 1 day). 
4. Comparative Pain of study donor sites during 1st week post-treatment (Day 7 ± 1 
day). 
5. Blinded Evaluator Overall Opinion POSAS Score of study donor sites at Week 
24. 
6. Patient Overall Opinion POSAS Score of study donor sites at Week 24 (reported 
by subjects 8 years of age or older, or by parent/guardian if subject is less than 8 
years of age). 
Each endpoint will be tested in a fixed hierarchical method at a one-sided 0.025 
significance level in the above order.  These secondary endpoints/hypotheses will only be 
evaluated if the null hypothesis for the primary endpoint is rejected in the appropriate 
direction, and each secondary endpoint will only be evaluated if the null hypothesis of 
equality, for the endpoint preceding it in the list above, is rejected in the appropriate 
direction. 
Tertiary Endpoints/ 
Data Collection 
Other tertiary endpoints: 
1. Investigator’s (unblinded) assessment of healing at all RECELL-treated areas 
including study donor sites will be documented for all visits. 
2. Subject (or parent/guardian) reported study donor site pain prior to and during 
dressing changes.  
3. Subject (or parent/guardian) reported study donor site itching score prior to 
dressing changes (Itch Man Scale). 
4. Pain score associated with dressing changes at study donor sites assessed by the 
health care provider performing the dressing change using the Face, Legs, 
Activity, Cry, Consolability (FLACC) scale. 
5. Blinding effectiveness at Week 4 and Week 24. 
Inclusion Criteria 
 
Subjects must meet all the follow criteria to be eligible: 
1. Male or female patients aged 1 through 16 years (inclusive) with a skin defect for 
which split-thickness autografting is indicated.  
2. The area of total injury or planned defect (excluding donor sites) is 5% to 25% 
Total Body Surface Area (TBSA), inclusive. 
3. Two discrete split-thickness donor sites of similar size (±25%) can be created in 
a similar non-articulating location (excluding the scalp) with each donor site 
representing a minimum of 1% TBSA. 
4. The patient and family member/parent/guardian are able to complete all follow-
up evaluations required by the study protocol. 
5. In the opinion of the investigator, the patient and/or parent/guardian must be able 
to: 
a. 
Understand the full nature and purpose of the study, including possible 
risks and adverse events, and 
b. Provide informed consent/assent as appropriate for study participation. 
6. The patient and/or parent/guardian agrees to abstain from any other treatment of 
the wound(s) for the duration of the study unless medically necessary and comply 
with all compulsory study procedures. 
7. The patient and/or parent/guardian agrees to abstain from enrollment in any other 
interventional clinical trial for the duration of the study. 
8. The patient and/or parent/guardian can understand instructions and give 
informed, voluntary, written consent. 
9. Life expectancy greater than 52 weeks. 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible for participation in the 
study: 

 
 
1. 
Prior autograft harvest at planned study donor sites. 
2. 
Patients with sepsis or hemodynamic instability. 
3. 
The patient has an infection under active management or other dermatologic 
condition at the planned donor sites or treatment areas. 
4. 
Patient (of reasonable age) or parent/guardian is unable to follow the protocol 
requirements. 
5. 
The patient has other concurrent conditions that in the opinion of the investigator 
may compromise patient safety or study objectives. 
6. 
Patients with a known hypersensitivity to trypsin or compound sodium lactate 
for irrigation.   
7. 
In post-pubescent girls, pregnant or breast-feeding (pregnancy test should be 
performed in accordance with local institutional requirements). 
8. 
Enrollment in a concurrent study in which the study treatment may confound the 
endpoints of this study. 
Statistical 
Consideration 
As the primary effectiveness outcome is an acute outcome and it is anticipated that healing 
data will be available for all (if not most) subjects, the sample size calculation is based on 
the paired t-test for inequality rather than a survival method.  Survival estimates are 
generally applicable to longer-term wound healing studies such as studies of chronic 
wounds where there is the expectation for missing outcomes (wounds not healing) and 
where the follow-up to observe the primary outcome of interest is prolonged raising 
concerns for a greater number of withdrawals; which is not the case for this study. 
 
After approximately 50% of the subjects have achieved healing on both wounds, a sample 
size re-estimation will be performed by an independent statistician and will be presented 
to the independent data monitoring committee (DMC). The sample size re-estimation 
analysis will be performed according to the Mehta & Pocock Promising Zone approach 
and the DMC may recommend adjusting the sample size upwards as indicated by the 
sample size re-estimation analysis, as long as the conditional power for success by the 
protocol-specified final sample size is in the promising zone (38% - 80%).  
 
The standard deviation is based on literature in which it is reported that the standard 
deviation for time to re-epithelialization of partial thickness injuries in children was four 
days. Thus, the standard deviation of the treatment difference could be as large as 5.6 days 
depending on the within-patient correlation on the primary endpoint (the lower the 
correlation, the larger the standard deviation). Assuming the true mean difference is 2.8 
days and conservatively assuming the standard deviation is 5.6 days, then with a sample 
size of 37 subjects, there is an 80% probability that the null hypothesis will be rejected at 
a significance level of 0.025 (one-sided). The randomized sample size will be increased to 
50 subjects primarily to gain additional RECELL device experience for the proposed 
indication as well as to account for missing endpoint data which is anticipated to be 
minimal. 
 
The primary effectiveness endpoint is time (in days) to complete closure of study donor 
sites. It is anticipated that RECELL treatment of donor sites will be superior to 
conventional treatment (Control) for the primary effectiveness endpoint. 
 
The Intent to Treat (ITT) population will consist of all enrolled subjects who are 
randomized with data analyzed according to randomized treatment assignment. This 
population will be utilized as a primary analysis population for the effectiveness endpoints. 
 
The Per Protocol (PP) population will consist of ITT subjects who do not have major 
protocol deviations with data analyzed according to treatment received.  This population 
will be utilized as a secondary analysis population for the primary effectiveness endpoints.