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 Standard of Care Dressings for Treatment of Partial-thickness Burns in Infants, Children and Adolescents (Aged 1-16 Years)
Phase: NA
Conditions: Burns
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 Standard of Care Dressings 
for Treatment of Partial-thickness Burns in Infants, Children and Adolescents 
(Aged 1 – 16 Years) 
 
 
 
Investigational Plan 
 
Study Number:  
 
CTP006-2 
Device:  
 
 
RECELL® Autologous Cell Harvesting Device 
Study Type: 
 
Pivotal Study 
IDE Reference Number: 
13053 
Issue Date/Version:  
December 11, 2020 / Revision 5 
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.  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). 
 
 
Print Name: __________________________________ 
Principal Investigator 
 
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 Standard of Care Dressings for Treatment 
of Partial-thickness Burns in Infants, Children and Adolescents (Aged 1–16 Years) 
Protocol No. 
CTP006-2 
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 Treatment 
Application of RES® prepared using the RECELL® Autologous Cell Harvesting 
Device to partial-thickness burns (dressed with Telfa™ Clear primary and 
Xeroform™ secondary wound dressings) 
Control Treatment 
Mepilex® Ag Wound Dressing (Mölnlycke Health Care) is a standardly employed 
dressing for second-degree/partial-thickness burns due to its non-adherent and 
antimicrobial properties. The layered dressing includes a flexible, absorbent 
polyurethane foam pad embedded with silver sulfate compound and vapor 
permeable film backing with a silicone layer covered with a polyethylene release 
film.  
Phase of Study 
Pivotal Study 
Proposed Indication for 
Use 
The RECELL Device is indicated for treatment of partial-thickness burns in patients 
1 year of age or greater. 
Primary Objectives 
To demonstrate that RECELL treatment of partial-thickness burn injuries, can safely 
and effectively increase the incidence of Day 10 healing compared with a 
standardized wound dressing. Also, the effects of both treatments on the incidence 
of conventional autografting, pain, itching, scarring, health-related quality of life and 
resource utilization will be investigated. 
Planned Enrollment 
To evaluate the primary endpoint, enrollment of 160 subjects is planned. 
 
This study utilizes an adaptive design with interim analysis for early stopping due to 
futility or positive outcome and, if necessary, sample size re-estimation in order to 
maintain adequate condition power. The maximum enrollment will be 300 subjects. 
Trial Design 
This is a prospective, parallel-arm, randomized (1:1), blinded evaluator, multicenter 
trial. Infants, children, and adolescents (aged from 1 through 16 years), male and 
female, with a burn injury that is no more than 30% of their total body surface area 
(TBSA) and no more than 10% TBSA is full-thickness burn injury, will be 
considered for participation.  
 
Randomization and assigned treatment must be performed within 72 hours of the 
burn injury for a subject to be treated within this study. 
 
Qualifying subjects will be randomized 1:1 either to treatment with RECELL or to 
Control (Mepilex® Ag Wound Dressing). Randomization will be stratified by 
investigational site and total burn area (<10% TBSA and ≥10% TBSA).  If there is 
more than one partial-thickness burn wound, the largest partial-thickness burn 
wound meeting eligibility requirements will be identified as the Index Burn (the burn 
wound that will be compared for effectiveness outcomes). The Index Burn will be a 
contiguous area at least 160 cm2 that excludes the face, hands, feet and genitalia.  
 

 
In order to evaluate the impact of study treatment on quality of life and health 
economic outcomes, unless clinical circumstances dictate otherwise, all of the 
subject’s partial-thickness burn wounds, including any non-index burn(s), should be 
treated at the initial procedure according to the randomized treatment assignment.  
 
For subjects randomized to RECELL, skin sample harvesting and treatment should 
be performed in accordance with the RECELL Instructions for Use. Prior to 
application of RES, necrotic tissue is to be excised. The skin sample size required 
for processing is approximately 1/80th of the area to be treated. RES may be applied 
to the RECELL donor site at the investigator’s discretion.  
 
For subjects randomized to Control, burn wounds should be cleaned per local 
standard practice prior to application of Mepilex® Ag Wound Dressing.   
Mepilex® Ag Wound Dressing will be applied in accordance with the 
manufacturer’s Instructions for Use. 
 
Subjects should be seen for dressing changes as clinically indicated.  
 
Primary Effectiveness Assessments: Day 10 and Day 28 post-treatment, the Index 
Burn will be evaluated via direct visualization by a qualified local clinical 
investigator blinded to treatment allocation (Blinded Evaluator) to assess Index Burn 
healing, unless the Index Burn has been autografted. 
 
At all follow-up visits, the Index Burn will be photographically documented using 
standardized digital imaging. From these images, the percent re-epithelialization 
will be determined via photographic planimetry by a third-party centralized image 
vendor. A random selection of digital tracings will be reviewed by an Independent 
Medical Monitor to confirm the correct tracing of re-epithelialized areas reported by 
a third-party centralized image vendor.  
 
During the acute follow-up period, the investigator will determine whether 
autografting of the Index Burn is required. Autografting is typically indicated when 
there are no signs of improvement or healing, when the investigator expects no 
further wound healing in the next 7 to 11 days, or when a contiguous area greater 
than 0.5% TBSA is unhealed. Index Burns requiring conventional autografting will 
be evaluated as clinically indicated. 
 
Standardized digital images of Index Burns taken during acute follow-up, including 
images taken the day the investigator made a decision to autograft will be presented, 
out of time sequence, to an Independent Medical Monitor (blinded to treatment 
allocation and investigator’s determination) to review. 
 
Longer-term follow-up visits will be performed at Weeks 8, 16, 24, 36 and 52 post-
treatment (irrespective whether a subject had conventional autografting of the Index 
Burn). 
 
At the Week 16, 24, 36 and 52 post-treatment visits, scar outcomes and disease-
specific quality of life will be assessed. Scar outcomes will be measured 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). Patient- and family-reported quality of life 
outcomes will be captured via the age-specific Burn Outcomes Questionnaire 
(BOQ). The BOQ evaluates several domains specific to longer-term burn outcomes 
including physical function, appearance, satisfaction and emotional health among 
others. Investigator treatment preference will be documented for each treating 
investigator, at each burn center, following the investigator’s last subject’s last visit. 

 
 
During the longer-term follow-up visits, the preferred method is in-person clinical 
visits, however (if necessary), these follow-up visits may be conducted remotely 
(e.g., via telemedicine) with the exception of the Week 52 visit.  
 
Treatment-related adverse events (e.g., infection, wound breakdown, etc.) are to be 
recorded for the Index and Non-Index Burn wounds as well as for donor sites. 
 
An interim analysis will be conducted after approximately 50% of total enrollment 
has reached the primary effectiveness endpoint (i.e., 80 subjects have completed the 
primary endpoint evaluation including confirmation of healing at Day 28).  At that 
time, study enrollment may be discontinued due to futility or demonstration of 
effectiveness.  If enrollment continues, a sample size re-estimation will be 
performed, and the sample size may be adjusted upwards to at most 300 subjects. 
 
Safety data will be reviewed and adjudicated by an Independent Medical Monitor. 
A Data Monitoring Committee will be responsible for interim review of safety and 
effectiveness data and will be responsible for reviewing data from the interim and 
sample size re-estimation analyses. 
Number of Trial Centers 
Up to 25 US trial centers with a specialty in pediatric burn care will participate. No 
center will contribute more than 25% 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 incidence of Index Burns with Day 10 healing 
post-treatment, evaluated by an observer blinded to treatment allocation, with 
confirmation at Day 28. If the Index Burn undergoes a secondary surgical treatment 
for closure (including conventional autografting) prior to the Day 28 visit, this will 
be considered an endpoint failure. 
 
The hypothesis to be evaluated is whether the incidence of Day 10 healing post-
treatment is greater (superior) with RECELL treatment vs. Control treatment. 
Safety Endpoints 
Safety will be evaluated in terms of treatment-related adverse events and serious 
device-related adverse events. 
Secondary Effectiveness 
Endpoints 
Specific secondary endpoints to be investigated for potential labeling claims include 
the following: 
1. Incidence of Index Burn Day 21 post-treatment healing (confirmed on Day 28). 
2. Percent area of Index Burn requiring autografting.  
3. Incidence of conventional autografting to achieve Index Burn healing.  
 
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 
1. Absolute area (cm2) of Index Burn requiring autografting. 
2. Index Burn pain scores at dressing changes assessed by the health care provider 
performing the dressing change using the Face, Legs, Activity, Cry, 
Consolability (FLACC) Scale.  
3. Subject reported Index Burn pain scores at dressing changes. 
4. Percent epithelialization of the Index Burn per digital planimetry. 
5. Index Burn POSAS scar ratings. 
6. BOQ Outcomes (raw scores and recovery curves for all domains), with baseline 
at Day 10. 

 
7. Investigator treatment preference. 
8. Health economics/medical resource utilization (determined using CRF data in 
conjunction with UB-04/CMS-1500 and/or similar hospital and physician claim 
forms for billing purposes to collect data associated with the initial hospital care 
and readmissions during follow-up as applicable). 
9. Index Burn Itch Man Scale ratings. 
Pre-Randomization 
Inclusion Criteria  
 
1. Male or female patients aged 1 through 16 years (inclusive) with a partial-
thickness thermal burn injury. 
2. The patient has a thermal burn injury that is: 
a. 
≤ 30% TBSA (exclusive of superficial areas) and 
b. ≤ 10% TBSA is a full-thickness burn. 
3. The Index Burn must be a clean partial-thickness burn injury ≥160 cm2 and 
between 2-20% BSA (inclusive). 
4. The Index Burn may not cover the face, hand, foot or the perineum/genitalia 
(Note: a patient with wounds in these areas may be enrolled but the Index Burn 
Area may not include these areas). 
5. The patient and/or parent/guardian agrees to comply with all compulsory study 
procedures and visit schedule. 
6. The patient and/or parent/guardian agrees to abstain from any other treatment 
for closure of the Index Burn for the duration of the study unless medically 
necessary. 
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. 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,  
b. Understand instruction, and  
c. Provide voluntary informed written consent/assent as appropriate for 
study participation.  
Pre-Randomization 
Exclusion Criteria  
1. Not able to understand English or Spanish. 
2. Burns caused by chemicals, electricity or radiation. 
3. Patients presenting with only 3rd-degree/full-thickness wounds which require 
immediate autografting. 
4. Burn injury has had prior treatment for definitive closure. 
5. Patients for whom use of sedation/general anesthesia is not medically 
appropriate. 
6. Superficial/trivial burns or burns that in the investigator’s opinion appear to be 
healing sufficiently such that care under this protocol would be inappropriate. 
7. Patient requires immediate or staged surgical procedures for closure of their 
partial-thickness burns. 
8. Conditions, e.g., previous burn injury to study area, poor nutritional status, 
poorly controlled diabetes mellitus (HbA1c >9%), that in the investigator’s 
opinion may compromise subject safety or trial objectives.  
9. Current use of medications, e.g., immunosuppressive agents (excluding inhaled 
corticosteroids), that in the investigator’s opinion may compromise subject 
safety or trial objectives. 
10. Inhalation injury. 
11. Active infection, cellulitis or need for immediate grafting at the planned 
treatment areas. 
12. Concerns for parent/guardian’s ability to provide appropriate follow-up care. 
13. Subjects with a known hypersensitivity to trypsin or compound sodium lactate 
for irrigation solution.   
14. Subjects with a known sensitivity to silver. 

 
15. In post-pubescent girls, pregnant or breast-feeding (pregnancy test should be 
performed in accordance with local institutional requirements). 
16. Immediate life-threatening condition or life expectancy less than one year. 
17. Previous randomization within this investigation. 
Post-Randomization 
(Prior to treatment) 
Eligibility Criteria 
Post-Randomization Inclusion: 
1. Patient randomized (and will be treated) within 72 hours from the time of the 
burn injury. 
2. Patient continues to meet all pre-randomization inclusion criteria. 
 
Post-Randomization Exclusion: 
1. Incidental finding of any pre-randomization exclusion criteria.  
 
Consented subjects who do not meet the post-randomization eligibility criteria and 
did not receive study treatment will be followed through the Day 28 visit and then 
withdrawn from the study.  The criteria for which exclusion was based will be 
documented. 
Statistical Considerations 
Based on medical input, the estimated proportion of subjects with confirmed day 10 
healing is anticipated to be approximately 75% for the Control group. It is estimated 
that the proportion of RECELL subjects with confirmed day 10 healing will be 
92.5%. Assuming power of 80%, using a one-sided z-test of proportions and one-
sided alpha of 0.025 requires 69 subjects per group (138 subjects total). The total 
sample size has been increased by 12% to 160 subjects to adjust for missing data. 
 
The hypothesis to be evaluated is whether the incidence of Day 10 healing post-
treatment (confirmed at Day 28 post-treatment) is greater (superior) with RECELL 
treatment vs. Control treatment. 
 
A formal unblinded interim analysis comparing treatments on the primary endpoint 
will be conducted once 50% of total enrollment has completed the primary 
effectiveness endpoint follow-up (i.e., 80 subjects have been randomized and 
reached the Day 28 healing confirmatory visit or would have reached the Day 28 
visit had they not prematurely withdrawn). 
 
The unblinded interim analysis will be based on O’Brien-Fleming stopping rules. At 
the interim look, the one-sided p-value will need to be less than or equal to 0.00153 
with results favoring RECELL in order to stop the study for reasons of 
overwhelming effectiveness of RECELL; the one-sided p-value will need to exceed 
0.45604 to stop the study for futility. The one-sided p-value at the final analysis 
needs to be less than or equal to 0.02496, rather than the usual 0.025 required for a 
study without an interim analysis.  This interim analysis will be based on patients 
with available primary endpoint data; there will no imputation of missing data at this 
interim analysis. 
 
The Intent to Treat (ITT) population will consist of all enrolled subjects who are 
randomized, with data analyzed according to randomized treatment assignment.  
 
The Modified Intent to Treat (mITT) Population will consist of all enrolled subjects 
who are randomized and treated, with data analyzed according to randomized 
treatment assignment. This population will be utilized as a primary analysis 
population for the primary and secondary effectiveness endpoints. 
 
Per Protocol (PP) Population will consist of mITT 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 and 
secondary effectiveness endpoints. 

 
The primary effectiveness endpoint is incidence of Index Burns with Day 10 healing, 
evaluated by an observer blinded to treatment allocation, with confirmation at Day 
28. If the Index Burn undergoes a secondary surgical treatment for closure (including 
conventional autografting) prior to the Day 28 visit, this will be considered an 
endpoint failure.