A Prospective Blinded Within-Subject Randomized Controlled Clinical Study to Investigate the Safety and Effectiveness of RECELL for Repigmentation of Stable Vitiligo Lesions
Phase: NA
Conditions: Vitiligo
Sponsor: Avita Medical

  
 
 
A Prospective Blinded Within-Subject Randomized Controlled Clinical Study 
to Investigate the Safety and Effectiveness of RECELL for Repigmentation of 
Stable Vitiligo Lesions 
 
Investigational Plan 
Study Number:  
 
CTP009 
Device:  
 
 
RECELL® Autologous Cell Harvesting Device 
Study Type:  
 
Pivotal Study 
Date / Revision:  
 
July 8, 2021 / Rev 4 
Sponsor:  
 
 
AVITA Medical  
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 

 
 
 
 
1.0 
PROTOCOL SYNOPSIS 
Title 
A Prospective Blinded Within-Subject Randomized Controlled Clinical Study to 
Investigate the Safety and Effectiveness of RECELL for Repigmentation of Stable 
Vitiligo Lesions 
Protocol No. 
CTP009 
Phase of Study 
Pivotal Study 
Proposed Indication 
for Use 
The RECELL® Autologous Cell Harvesting Device is intended for use at the 
patient’s point-of-care for the safe and rapid preparation of Spray-On Skin™ Cells 
from a small sample of a patient’s own skin. The cell suspension prepared using 
the RECELL System is suitable for application to a prepared treatment area for 
repigmentation of stable vitiligo lesions. 
Primary Objective 
To evaluate the application of Spray-On Skin™ Cells, prepared using the 
RECELL® Device, for safe and effective repigmentation of ablated stable vitiligo 
lesions. 
Study Population 
Pivotal Cohort 
The pivotal cohort will consist of no fewer than 23 subjects. This study utilizes an 
adaptive design with an interim analysis planned for the purposes of sample size 
re-estimation (to achieve adequate conditional power). There will be a maximum 
of 46 subjects in the pivotal cohort. 
 
Roll-in Cohort  
Up to two roll-in cohort patients may be randomized at each investigational site for 
purposes of ensuring proficiency with the investigational device and study 
procedures prior to advancing to enrollment in the pivotal cohort. Any subject 
randomized prior to Rev 3 of the investigational plan will be considered a roll-in 
cohort subject. All roll-in subjects must meet the same eligibility criteria, will 
undergo the same study procedures and follow-up assessments as the pivotal cohort 
subjects; however, data from the roll-in cohort of subjects will be analyzed 
separately from the pivotal cohort. A maximum of 35 subjects total roll-in cohort 
subjects (including those randomized prior to Rev 3) are anticipated in addition to 
the planned pivotal cohort subjects. Subjects in the roll-in cohort may not re-enroll 
in the pivotal cohort. 
 
There will be a maximum of 81 subjects from both cohorts.  
Number of Trial Centers 
The study will be executed at no more than 15 centers in the United States. 
Clinical 
Justification/Clinical 
Benefit 
The RECELL® Autologous Cell Harvesting Device has been safely and effectively 
used to prepare and apply cell suspension that includes pigment-producing cells 
(melanocytes) for treatment of burn wounds. Patients without functional 
melanocytes and who are candidates for application of skin cells to depigmented 
areas of skin may benefit from point of care use of the RECELL Device. 
Investigational Treatment 
Skin cell suspension at 1:20 expansion ratio (donor area : recipient area), prepared 
using the RECELL System, will be applied to an ablated (de-epithelialized) area of 
depigmentation, followed by targeted phototherapy using NB-UVB.   
Control 
Each subject will serve as their own Control, with a depigmented area receiving no 
RECELL treatment but receiving the same targeted NB-UVB as the investigational 
treatment area. 

 
 
 
 
Study Design 
This is a prospective blinded randomized within-subject controlled study to 
evaluate the clinical performance of RECELL for repigmentation of stable, 
depigmented lesions in subjects 18 years or greater. The trial will evaluate matched 
pairs of stable depigmented study areas. After identification of two study areas, one 
study area will be randomly assigned to RECELL, and the other will serve as the 
Control. 
 
Follow-up visits during the effectiveness period will be at Weeks 1, 4, 12 and 24 
post-treatment followed by a durability period that will include follow-up visits at 
Weeks 36 and 52 post-treatment. Acute healing, pigmentation, and compliance 
with phototherapy will be evaluated. Treatment-related and serious adverse events 
will be documented throughout the duration of the study. For all study subjects and 
visits, study areas will be documented using standardized digital photography. 
 
Pigmentation of all study areas will be determined via centralized image 
interpretation by an expert dermatological panel blinded to treatment allocation 
(i.e., Central Review Committee, CRC) to decrease variability. In addition to the 
CRC, an assessment of pigmentation and study area Vitiligo Area Scoring Index 
(VASI) will be performed by the investigator for each study area. To assess 
durability of responding RECELL-treated study areas at Week 52, the investigator 
and the CRC will confirm that ≥ 80% of the pigmentation remains relative to the 
subject’s Week 24 photograph. 
 
Patient reported outcomes will be captured using the Vitiligo Noticeability Scale 
(VNS), Patient Global Impression of Change-Vitiligo (PaGIC-V), and a subject 
global treatment success assessment.  
 
After completion of the Week 24 (non-responders) or Week 52 (responders) visit, 
the subject may be given the option for RECELL treatment of their depigmented 
study area(s). 
Primary Effectiveness 
Endpoint 
The primary effectiveness endpoint is the proportion of Responders for RECELL-
treated areas versus Control at Week 24. Responders are defined as study areas 
achieving ≥ 80% pigmentation as determined by the Central Review Committee. 
Secondary Effectiveness 
Endpoints 
1. Central Review Committee categorization of repigmentation (0-25%, 26-50%, 
51-79% and 80-100%) at Week 24 
2. Central Review Committee assessment of color matching for the study areas 
at Week 24  
Tertiary (Exploratory) 
Measures 
1. Subject and investigator global treatment success and donor site satisfaction  
2. Subject-reported Vitiligo Noticeability Score vs baseline (based on 
photographs) 
3. Investigator assessment of pigmentation responder (≥ 80% pigmentation) for 
the study areas at Week 24 
4. Investigator assessment of repigmentation category (ordinal data) for the study 
areas 
5. CRC and investigator assessment of pigmentation for the study areas at Weeks 
36 and 52 
6. Investigator study area VASI scores, change from baseline  
7. Investigator assessment of color matching for the study areas  
8. CRC assessment of color matching for the study areas at Weeks 36 and 52 
9. Patient Global Impression of Change-Vitiligo (PaGIC-V)  
10. Repigmentation durability at Week 52 as assessed by the investigator and CRC 

 
 
 
Safety Evaluations 
Safety will be evaluated in terms of healing and scar outcomes, and treatment-
related adverse events. 
 
Safety variables that will be evaluated at the study areas and donor sites: 
1. Incomplete healing (<100%) at Week 4 
2. Infection 
3. Koebnerization 
4. Donor and recipient site scar requiring surgical treatment 
5. Milia requiring medical intervention 
6. Other treatment-related and serious adverse events 
Inclusion Criteria 
 
Subjects must meet all the following criteria to be eligible: 
1. Focal, segmental or generalized (i.e., nonsegmental) stable vitiligo, defined as 
no new depigmented areas nor any depigmented areas that have expanded in 
size within the preceding 12 months, regardless of whether the areas are 
intended to be used as study areas.  
1a.  Photo documentation (current and at least 12 months prior) of the patient’s 
depigmented areas have been evaluated as stable by an independent Screening 
Committee. 
2. The patient has not undergone topical treatment (e.g., steroids, tacrolimus) for 
the study areas within the past 90 days. 
3. The patient has not undergone phototherapy (e.g., NB-UVB) for the study 
areas within the past 90 days. 
4. The patient is a candidate for surgical intervention of a depigmented area, 
defined as a patient who has previously been compliant with but has not 
satisfactorily responded to both: 
a. 
topical therapy and  
b. a minimum of 3 months of phototherapy. 
5. The patient must have two study areas available for treatment that: 
a. 
are of similar size (±50%), 
b. are between 16cm2 and 456cm2 (contiguous), 
c. 
are similarly sun exposed, 
d. have the same extent of leukotrichia, and  
e. 
are judged clinically as ≥90% depigmented (by area).   
6. The patient is 18 years of age or older. 
7. The patient is willing and able to comply with post-treatment at-home 
phototherapy and all follow-up evaluations required by the study protocol. 
8. The patient agrees to abstain from any other treatment of the study areas for 
the duration of his/her participation in the study (52 weeks). 
9. The patient agrees to abstain from enrollment in any other interventional 
clinical trial for the duration of his/her participation in the study (52 weeks). 
10. In the opinion of the investigator, the patient must be able to: 
a. 
Understand the full nature and purpose of the study, including 
possible risks and adverse events, 
b. Understand instructions, and  
c. 
Provide voluntary written informed consent. 

 
 
 
 
Exclusion Criteria 
Subjects who meet any of the following criteria are not eligible: 
1. The study areas selected have concomitant dermatologic conditions other than 
vitiligo. 
2. The study area selected for treatment includes the lips, eyelids, plantar surface 
of feet, palmar surface of hands, fingertips, wrists, ankles, elbows, or knees. 
3. The patient is unable to undergo the treatment area preparation. 
4. Patients who are pregnant. 
5. Patients with any of the following: 
a. 
universalis vitiligo, 
b. depigmented areas over >30% of their body surface area,  
c. 
depigmented lips and fingertips (lip-tip vitiligo), or 
d. > 3 depigmented fingertips, defined as depigmentation of the dorsal 
aspect of the fingertip from the distal interphalangeal joint to the tip 
of the digit. 
6. Patients with recent history (within previous 12 months) of: 
a. 
Koebnerization,  
b. confetti-like, or  
c. 
trichrome lesions. 
7. Patients with a history of keloid formation. 
8. Patients who have used a tanning salon in the past 60 days. 
9. The patient has other concurrent conditions that in the opinion of the 
investigator may compromise patient safety or study objectives. 
10. Current use of medications (e.g., anticoagulants such as heparin or warfarin) 
that in the investigator’s opinion may compromise patient safety or trial 
objectives. 
11. The patient has a known hypersensitivity to trypsin or compound sodium 
lactate for irrigation (Hartmann’s) solution. 
12. Life expectancy is less than 1 year. 
Study-specific procedure 
highlights 
• 
Two depigmented study areas will be outlined and labeled (A and B). 
• 
Randomization to assign area A or B to RECELL will be performed in the 
EDC. 
• 
Donor skin will be harvested under local anesthetic sufficient to prepare 
suspension for both the recipient and donor sites. 
• 
The RECELL-assigned study area will be ablated to a sufficient depth to 
remove the epidermis and expose the papillary dermis. 
• 
Spray-On Skin™ Cells will be applied to the RECELL-assigned study area 
using a 1:20 expansion ratio.  
• 
Standardized dressings will be applied to the RECELL-treated study area and 
donor site. 
• 
 NB-UVB phototherapy 
 will 
commence on both study areas after dressings are no longer in place.  

 
 
 
 
Screening Committee (SC) 
Post-consent and prior to randomization, investigational sites must submit 
photographic evidence (with date stamp or other evidence of date of image 
acquisition) of stable vitiligo for each subject that includes: 
1) Current photos of the subject’s depigmented areas obtained during 
screening  
2) Current photos of the subject’s dorsal hands displaying all fingertips 
obtained during screening  
3) Historic photos ≥ 12 months prior of the subject’s depigmented areas  
 
The independent SC will consist of a minimum of 3 board-certified dermatologists. 
Each patient being considered for treatment will have the photographic evidence 
outlined above in addition to other relevant medical history reviewed by a minimum 
of 3 committee members. Two (2) of 3 members must concur the photographs are 
of stable vitiligo prior to the investigational site proceeding with randomization and 
treatment. The SC will be blinded to which investigational site the photographs 
originated from. 
Central Review Committee 
(CRC) 
Three independent board-certified dermatologists (Central Review Committee, 
CRC) will be selected based on specific selection criteria for the purpose of 
providing blinded adjudication to determine whether successful repigmentation of 
the study areas (≥ 80%) have been achieved and if not, then to determine 
categorization of repigmentation. The CRC will be blinded to the study site, 
treatment assignment, and the investigator’s determination of repigmentation for 
each study area. The adjudicated results will be used in the primary analysis.  
 
The CRC will be governed under a charter that will be approved by the committee, 
and that will contain the guidance and rules under which they will review and 
adjudicate data. Assessments of repigmentation at 24 weeks post- treatment 
(relative to baseline) will be assessed by all three members of the CRC. If two CRC 
members agree, adjudication of that subject’s timepoint will be deemed complete. 
If there are any discordant cases (i.e., agreement not achieved between two CRC 
members), the committee will review the case together with the majority ruling (2/3 
CRC members in agreement) serving as the final adjudication. The CRC members 
will record their review independently. Panel assessments will be conducted 
consistent with consensus guidance published by the Vitiligo Global Issues 
Consensus Group (VGICG) for the evaluation of patients with vitiligo using a 
reference atlas developed by the VGICG depicting vitiligo repigmentation patterns 
and color match. 

 
 
 
 
Statistical considerations 
The sample size for this trial was determined based on the primary effectiveness 
endpoint of responders at 24 weeks. The trial is designed to test if RECELL 
treatment using an expansion ratio of 1:20 is superior to Control. An alpha level of 
0.025 is utilized for hypothesis testing. The trial will incorporate an unblinded 
interim analysis for purposes of sample size re-estimation after approximately half 
the planned subjects reach 24 weeks. The interim analysis will be conducted 
according to the promising zone method of Mehta and Pocock (2011), allowing for 
up to twice the original planned sample size. 
 
Assuming 5% responders in Control and 60% responders for RECELL, 20 subjects 
yields 90% power, one-sided 0.025 level of significance to demonstrate RECELL 
superiority versus Control. This assumes a 10% superiority margin relative to 
Control.  
 
Anticipating 10% lost to follow-up, 23 subjects are planned. An interim analysis 
for purposes of sample size re-estimation will occur when 11 subjects have 24-
week follow-up data. The sample size may be increased based on the results of this 
interim analysis to a maximum of 46 subjects. 
 
Note that it is possible that, depending on rate of subject accrual, the interim 
analysis of 24-week data may not occur until after 23 subjects have already been 
enrolled.