A Pilot Study to Evaluate a Temporary Skin Substitute (Spincare® Matrix) for Wound Healing in RDEB Patients
Phase: NA
Conditions: Recessive Dystrophic Epidermolysis Bullosa
Sponsor: Stanford University

 
 
 
 
A Pilot Study to Evaluate a Temporary Skin Substitute 
(Spincare® Matrix) for Wound Healing in RDEB Patients 
 
Study Protocol and Statistical Analysis Plan 
NCT05944250   
June 5, 2024 

Protocol Number IRB-69575 
Confidential
 
 
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A Pilot Study to Evaluate a Temporary Skin Substitute 
(Spincare® Matrix) for Wound Healing  
in RDEB Patients 
 
 
Jean Y Tang 
Clinical Research Protocol 
 
A Pilot Study to Evaluate a Temporary Skin Substitute (Spincare™ Matrix) for 
Wound Healing in RDEB patients 
 
Protocol Number: 
IRB-69575 
Version Date: 
05 JUNE 2024  
Investigational Device: 
Spincare  
Study Phase: 
Phase 1 (pilot study) 
Sponsor-Investigator: 
Jean Y Tang  
450 Broadway St,  
Stanford School of Medicine North Campus, 
  
Redwood City 
CA 94063 
Funding Organization: 
EB Research Partnership 
Site Investigator:  
Jean Y Tang  
650-725-7152 
 
 
tangy@stanford.edu 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1.0 
PURPOSE OF THE INVESTIGATION .................................................. 10 
1.1  Name of investigational device .............................................................. 10 
1.2 
Intended use of the investigational device ............................................. 10 
1.3 
Objectives of the clinical investigation ................................................... 10 
1.3.1 
Primary objective ................................................................................................................. 10 
1.3.2 
Secondary objective(s) ........................................................................................................ 10 
1.4 
Anticipated duration of the clinical investigation .................................... 10 
2.0 
CLINICAL PROTOCOL ........................................................................ 11 
2.1 
Protocol number and title ....................................................................... 11 
2.2 
Protocol version number and date ......................................................... 11 
2.3 
Study design .......................................................................................... 11 
2.3.1 
General study design ........................................................................................................... 11 
2.3.2 
Study design schematic ....................................................................................................... 12 
2.4 
Subject selection ................................................................................... 12 
2.4.1 
General characteristics of the proposed subject population(s) ............................................ 12 
2.4.2 
Anticipated number of research subjects ............................................................................. 12 
2.4.3 
Inclusion criteria ................................................................................................................... 13 
2.4.4  
Exclusion criteria ................................................................................................................. 13 
2.5 
Study procedures .................................................................................. 13 
2.5.1 
Screening procedures.......................................................................................................... 13 
2.5.2 
Study treatment or diagnostic product procedures .............................................................. 13 
2.5.3 
Allocation to treatment ......................................................................................................... 15 
2.5.4  
Unblinding ............................................................................................................................ 15 
2.5.5 
Treatment/matrix adherence ................................................................................................ 16 
2.5.6 
Withdrawal of subjects due to non-compliance .................................................................... 16 
2.5.7 
Procedures to assess efficacy ............................................................................................. 16 
2.5.8 
Procedures to assess safety ................................................................................................ 16 
2.5.9 
Schedule of study visits ....................................................................................................... 17 
2.6 
Study outcome evaluations ................................................................... 19 
2.6.1 
Study endpoints ................................................................................................................... 19 
2.6.2 
Sample size determination .................................................................................................. 19 
2.6.3 
Outcome data and data analysis ......................................................................................... 20 
3.0 
RISK ANALYSIS ................................................................................... 20 
3.1 
Anticipated risks. ................................................................................... 20 
3.2 
Adverse event reporting ........................................................................ 20 
3.2.1 
Adverse event definitions ..................................................................................................... 20 

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3.2.2  
Eliciting adverse effect information ...................................................................................... 20 
3.2.3  
Recording and assessment of adverse effects .................................................................... 20 
3.2.5 
Causality and severity assessment...................................................................................... 21 
3.2.6 
Reporting adverse effects to the FDA .................................................................................. 21 
3.2.5 
Reporting adverse effects to the responsible IRB ................................................................ 21 
3.3 
Withdrawal of subjects due to adverse effects ...................................... 21 
4.0 
DESCRIPTION OF THE INVESTIGATIONAL DEVICE ........................ 22 
5.0 
MONITORING PROCEDURES ............................................................. 22 
6.0 
LABELING ............................................................................................ 22 
7.0 
INFORMED CONSENT ......................................................................... 22 
8.0 
IRB INFORMATION .............................................................................. 23 
9.0 
ADDITIONAL RECORDS AND REPORTS .......................................... 23 
9.1 
Data handling and record-keeping ........................................................ 23 
9.2 
Record maintenance and retention ....................................................... 23 
 
 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
QC 
Quality Control 
PI 
Principal Investigator 
UADE 
Unanticipated Adverse Device Effect 
 
 
 

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PROTOCOL SYNOPSIS 
TITLE 
A Pilot Study to Evaluate a Temporary Skin Substitute 
(Spincare™ Matrix) for Wound Healing in RDEB patients 
 
REGULATORY 
SPONSOR 
Jean Y Tang, MD, PhD 
FUNDING 
ORGANIZATION 
EB Research Partnership 
NUMBER OF SITES 
Single site 
RATIONALE 
Of the various EB subtypes, it is well known that 
recessive dystrophic epidermolysis bullosa (RDEB) 
patients suffer from the most severe skin wounds. In this 
pilot study we will enroll RDEB patients due to their need 
for specialized wound care, which is typically more 
complex and frequent than other types of EB. Therapies 
that reduce pain and the size and severity of wounds 
have also been reported as the main priorities for RDEB 
patients and caregivers. There are limited therapies 
approved in the US for the treatment of EB and there has 
been an exponential rise in EB-related studies. The 
mainstay of treatment is supportive with non-adhesive 
wound dressings.  
With the lack of therapies available to address the 
multitude of RDEB needs and the slow pace of EB 
research, we propose to evaluate the matrix device as a 
suitable and safe device for application of a matrix wound 
dressing to EB wounds. This study is looking at 
preliminary wound efficacy signals and tolerability. 
Results of this pilot study would inform the design of 
larger trials evaluating the suitability of the device as a 
vehicle in delivering COL7A1 gene-corrected skin cells for 
healing of RDEB wounds. This is currently under 
research development by Dr Anthony Oro’s Lab at 
Stanford.  
 
STUDY DESIGN 
This is a single-center, randomized feasibility study that 
offers an Open-Label Phase upon completion of the 
Randomized Phase. 
PRIMARY OBJECTIVE To assess the preliminary efficacy of matrix treatment in 
RDEB wound 
To assess safety profile of matrix treatment in RDEB 
wound 
 

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SECONDARY 
OBJECTIVES 
To assess improvement in wound pain with matrix 
treatment in RDEB wound 
To assess improvement in wound itch with matrix 
treatment in RDEB wound 
To assess caregiver responses on wound dressing ease 
of use with matrix treated wounds  
To compare the change in wound cultures between 
matrix treated wounds vs control wounds  
NUMBER OF 
SUBJECTS 
6-10 subjects for enrollment of at least 20 wound pairs  
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
Clinical and/or genetic diagnosis of RDEB by a 
dermatologist, age 6 years or older willing and able to 
give consent/assent and have at least 6 wounds (3 
wound pairs) each with an area of 10cm2 or greater 
located at any site (excluding face and genital skin). The 
first patient that will be enrolled is an adult patient before 
the recruitment of pediatric patients.  Wounds must be 
present for at least 4 weeks and able to be classified as 
recurrent wounds (wounds that heal within 12 weeks but 
then re-blister) vs chronic open (older than 12 weeks).  
 
Exclusion Criteria: 
Actively infected wounds with pus (colonized wounds are 
eligible), areas that have had squamous cell carcinoma 
(SCC), areas on the face and genitals, and areas that 
have been treated with investigational therapies in the 
past 3 months. 
INVESTIGATIONAL 
DEVICE / INTENDED 
USE 
Spincare  
 
The Spincare matrix is delivered from a portable, hand-
held device that produces an electrospun healing matrix 
made of biocompatible materials that attaches directly to 
the wound bed. 
CONTROL GROUP 
OR OTHER STUDY 
ARMS (if applicable) 
Standard of care non-adhesive wound dressings and 
bandage changes currently used. 
 
DURATION OF 
SUBJECT 
PARTICIPATION AND 
DURATION OF 
STUDY 
Subjects will be on study for up to 4 months 
Screening:  performed over phone and then virtually (up 
to 30 days before Day 0 treatment day) 
Treatment:  1-3 days (subjects to attend clinic) 
Follow-up:  4 months 
Open-Label Phase:  4 months 
The total duration of the study is expected to be 1 year. 4 
months for subject recruitment and 6 months for final 
subject follow-up is anticipated. 

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CONCOMMITANT 
MEDICATIONS 
Allowed: current EB medications (i.e., pain meds, 
vitamins, iron infusions, antibiotic ointments, oral 
antibiotics if needed). 
 
Prohibited: none 
Efficacy Evaluations 
Greater than 90% wound closure, patient reported 
outcomes in pain and itch sensation  
Primary endpoint 
Comparison of the duration of wound closure (weeks) of 
matrix treated wounds vs control wounds from baseline to 
Month 4. Wound photos will be captured at least every 2 
weeks by the patient and/or caregivers. The matrix will be 
applied initially in clinic and afterwards patients/caregivers 
are allowed to apply the Spincare treatment (up to once a 
week) to the designated treatment wounds if required. 
They will receive adequate training at the in-person 
and/or remotely visits before applying it. 
Secondary endpoints 
1. Comparison of application site adverse events (burning, 
erythema, pain) between matrix treated wounds vs 
control wounds after application. 
 
2. Comparison of wound pain (Wong-Baker FACES scale) 
between matrix treated wounds vs control wounds at 
Month 1, Month 2, Month 3, Month 4 (prior to 
application). More frequent timepoints may be 
requested. 
 
3. Comparison of wound itch [Itch Severity Scale (adults) / 
Itchy Man scale (minors)] between matrix treated 
wounds vs control wounds at Month 1, Month 2, Month 
3, Month 4 (prior to application). More frequent 
timepoints may be requested. 
 
4. Comparison of wounds that reach >50% healing from 
baseline in matrix vs control wounds at month 1, 2, 3, 4. 
 
5. Comparison of wounds that reach >70% healing from 
baseline in matrix vs control wounds at month 1, 2, 3, 4. 
 
Other Evaluations 
1. Comparison of caregiver responses on wound 
dressing ease of use on matrix treated wounds vs 
control wounds with the Caregiver Global Impression 
of Change survey (CaGI-C) at Month 3 and Month 4. 
 

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2. Comparison of change in wound cultures between 
matrix treated wounds vs control wounds at Month 2 
and Month 4.  
Safety Evaluations 
Wound evaluation e.g. presence of infection or skin 
cancer and documentation of adverse events. 
Planned Interim 
Analyses  
None. 1 adult subject to be enrolled first to ensure 
tolerability and safety before treating pediatric EB 
subjects > 6 years of age. 
STATISTICS 
Primary Analysis Plan 
Sample size calculation:  
We calculated that a sample size of 40 wounds (20 
matrix-treated vs 20 untreated) would give us 90% power 
to detect a difference of 8.5 vs 6 weeks (SD=3) of wound 
closure duration between matrix treated vs untreated 
wounds with a two-sided alpha of 0.05.  
Recruitment plan:  
We will recruit our cohort of 6-10 patients from various 
settings including the Stanford EB clinic (~100 RDEB 
patients), our clinical research database (75 RDEB 
patients), and the Epidermolysis Bullosa Clinical 
Research Consortium (EBCRC) (290 RDEB patients). 
Many of these patients have already received a clinical 
and/or genetic diagnosis of RDEB and have detailed 
medical and wound histories recorded 
Rationale for Number 
of Subjects 
This sample size calculation is based on our prior natural 
history study of 720 RDEB wounds for 6 months in 13 
RDEB adult and pediatric participants. We anticipate that 
the majority of pediatric wounds will be the recurrent type. 
If the Spincare matrix decreases the duration of wound 
closure, then this clinical trial would show a novel wound 
healing device that may improve wound closure duration 
in difficult to heal RDEB wounds. We would assess the 
secondary endpoints to determine if a 2.5 week longer 
wound closure is clinically meaningful and associated 
with wound specific decreases in pain and itch.  
 
 

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1.0 
PURPOSE OF THE INVESTIGATION 
 
1.1  
Name of investigational device 
Spincare matrix 
 
1.2 
Intended use of the investigational device 
The Spincare device, developed by Nanomedic, is the first portable tool that 
delivers an electrospun, nanofibrous matrix dressing to wounds to promote 
healing that is approved in Europe. The aim of this pilot study is to determine the 
suitability of this device in RDEB wounds and assess its wound healing 
properties, safety and tolerability, particularly in the EB population. 
 
1.3 
Objectives of the clinical investigation 
1.3.1 Primary objective 
1. Evaluate the efficacy and safety of the device on wounds in patients 
with recessive dystrophic epidermolysis bullosa. 
1.3.2 Secondary objective(s) 
2. To evaluate the improvement in patient reported pain and itch 
sensation with the matrix treatment. 
 
3. To evaluate patient and caregiver responses on wound dressing ease 
of use on matrix treated wounds vs control wounds with the Caregiver 
Global Impression of Change survey (CrGI). 
 
4. To compare the change in wound cultures between matrix treated 
wounds vs control wounds at Month 2 and Month 4.  
 
1.4 
Anticipated duration of the clinical investigation: 10 months  

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2.0 
CLINICAL PROTOCOL 
 
2.1 
Protocol number and title  
IRB-69575: A Pilot Study to Evaluate a Temporary Skin Substitute (Spincare™ 
Matrix) for Wound Healing in RDEB patients 
 
2.2 
Protocol version number and date  
Version 4.0, 05 June 2024 
   
2.3 
Study design 
2.3.1 General study design 
Pilot study in 6-10 subjects where wounds will be randomized 1:1 to matrix or no 
treatment (control): Patients will be asked to review and sign the informed 
consent form. The matrix will be applied to randomized treatment wounds 
(computer generated randomization), along with a non-adhesive bandage as a 
protective layer. At the time of matrix application, the investigator will score 
amount of wound burning, pain, or other adverse events. Non-treated wounds 
will have the patient’s standard of care, and the non-adhesive bandage applied. 
Reapplication of matrix treatment may be required soon after the initial 
application depending on how well the matrix has propagated with the first 
application. Subjects and caregivers will be trained on how to take photos. We 
will ensure that photos of the face are NOT included to protect patients' 
confidentiality. One day after a wound examination will be performed in clinic. 
The investigator will assess the adherence of the matrix, and any adverse events 
(AEs).  
Thereafter a caregiver may travel to the participants home to apply the matrix 
device to randomized, treated wounds once a month or more frequently if 
required (up to once-a-week application is allowed, the patient will record when 
they have applied the matrix treatment at home and the reason). Spray 
application(s) may be skipped at the discretion of the PI to address any concerns 
or adverse events.  Investigators will perform remote monitoring (via phone call 
or virtual platform) at Week 1, Week 2, Month 1, Month 2, Month 3 and Month 4 
(additional interim visits may be required) to assess for adverse events and track 
progress. Additional photographs will be taken, and investigators will use 
Telehealth to monitor for healing and safety reporting. Compliance is verified by 
bi-weekly photographs. Wound swabs of treated and untreated wounds will be 
taken prior to spray treatment and at Month 2 and Month 4. After Month 1, 
patients are given the option to not put any dressings on their wounds if this is 
medically acceptable and in line with the patient preference. Throughout the visit 
wound closure assessments may not be always possible if the Spincare matrix is 
still intact and this will be indicated on the source document. No Spincare 
treatment is to be applied 2 weeks prior to the end of the visit to allow for wound 
size measurement.  

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After the completion of the 4-month randomized phase, patients will be allowed 
to choose to enroll in an Open-Label Phase for an additional 4 months. 
Investigators will conduct remote monitoring on a monthly basis to assess 
adverse events and wound healing.
2.3.2 Study design schematic
2.4
Subject selection
2.4.1 General characteristics of the proposed subject population(s)
Patients aged 6-65 years old with a clinical and/or genetic diagnosis of recessive 
dystrophic epidermolysis bullosa. This target population was chosen as they
suffer from large painful wounds usually resistant to conventional treatment and
would benefit the most from matrix treatment with the Spincare device.
2.4.2 Anticipated number of research subjects
6-10 patients are planned to be recruited in the study.
Open-Label Phase (optional)
1. Selection of up to 10 wounds (previously randomized and/or new wounds)
2. Caregiver/Participant will assist with reapplication if needed (up to once a week application) 
3. Telehealth visits to assess efficacy and safety endpoints
Remote Visits
1. Caregiver will assist with reapplication if needed (up to once a week application) 
2.Telehealth to assess efficacy and safety endpoints
Spincare matrix is applied
1. Randomized wounds will be treated with Spincare matrix by investigator on Day 0
2. On Day 1 wounds are reassessed, Day 2  (optional, if needed at the discretion of the PI)
Screening
Patients will be screened over the phone to enquire about eligibility and interest in participation followed by a virtual 
meeting to assess eligibility of wounds 

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2.4.3 Inclusion criteria 
1. 
Subject has a clinical and/or genetic diagnosis of RDEB by a 
dermatologist; 
2. 
Subject is age 6 years or older willing and able to give consent/assent;  
3. 
Subject has at least 6 wounds (3 wound pairs) each with an area of 10cm2 
or greater located at any site (excluding face and genital skin);  
4. 
Subject wounds must be present for at least 4 weeks.  
2.4.4  Exclusion criteria 
1. 
Actively infected wounds with pus (colonized wounds are eligible); 
2. 
Wound areas that have had squamous cell carcinoma (SCC); 
3. 
Wound areas on the face and genitals; 
4. 
Wound areas that have been treated with investigational therapies in the 
past 3 months. 
 
2.5 
Study procedures 
2.5.1 Screening procedures 
Patients will be screened based on the inclusion and exclusion criteria. This will 
be initially performed over the phone. If eligible a virtual meeting will be 
organized, and patients will be asked to review and sign the informed consent 
form after which the wounds would be assessed in terms of suitability. 
2.5.2 Study treatment or diagnostic product procedures 
The Spincare device produces a wound dressing matrix that is sprayed to the 
wound bed. It uses a laser system to help with correct distance position to 
produce a uniform matrix that is electrospun to the wound bed. The device is 
currently available in Israel and 11 European countries but is not FDA-approved 
or cleared on any indications. In the current literature the main indications are 
acute and chronic wounds, partial thickness burns and ulcers and the matrix 
treatment has been used in more than 20 countries so far. A case study of 
Spincare treatment in EB has been described. 
 
A full body wound examination will be performed by the investigator and 
target wound areas will be identified. All eligible wound sites will be randomized 
for matrix treatment versus standard of care wound dressings (6 wounds, or 3 
wound pairs). The matrix will be applied to randomized treatment wounds, along 
with a non-adhesive bandage (e.g. Telfa, Mepitel, Rylon, etc.) as a protective 
layer. At the time of matrix application, the investigator will ask about any 
potential wound burning sensations, pain, or other adverse events. Non-treated 
wounds will have the patient’s standard of care and non-adhesive bandage 
applied. Subjects and caregivers will be trained on how to take photos. Wound 
pain and itch are captured at least every 2 weeks.  
 
The matrix treatment will be applied on Day 0 in clinic. Day 1 visit will be 
mandatory to assess for any adverse events (Day 2 is optional and may be 
required particularly if AEs have occurred and this will be at the discretion of the 

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PI). Subsequent applications will be performed by a caregiver if needed up to 
once a week.  
 
Detailed Schedule: 
 
Randomized phase: 
Day 0 – Spincare would be applied to wounds after randomization process and 
covered with a non-adhesive dressing. Reapplication of matrix treatment may be 
required depending on how well the matrix has adhered with the first application. 
The need for this will be assessed by the investigators.  
Day 1 – A wound examination will be performed in clinic one day after the initial 
application. The investigator will assess the adherence of the matrix, and any 
adverse events (AEs).  
Day 2 is optional and may be required if medically indicated at the discretion of 
the PI. 
Week 1, Week 2, and Months 1, 2, 3, 4 – Investigators will arrange telehealth 
assessment at Week 1, Week 2, Month 1, Month 2, Month 3 and Month 4 
(additional interim phone call visits/telehealth assessment at Week 6, Week 10 
and Week 14, or more frequently, if deemed necessary). A caregiver may travel 
to the participants home to apply the matrix device to randomized, treated 
wounds (up to once a week if needed, they will record the date of application and 
the reason). Additional photographs will be taken, and investigators will use 
Telehealth to monitor for healing and safety reporting. At the time of matrix 
application, the caregiver will score amount of wound burning, pain, or other 
adverse events. Matrix will not be applied after Week 14 to ensure the final 
wound assessment at Month 4. 
Month 4 – Telehealth (End of Randomized Phase) Visit: The investigator will 
virtually assess wound healing compared to baseline photographs in the treated 
and control wounds. Digital photographs of the treatment and control wounds will 
be taken with a ruler by the caregiver/participant and sent to the investigator. All 
wound photos will be stored and reviewed on the REDCap. The participant’s 
preference to enroll on the Open-Label Phase will be assessed. 
 
Open-Label Phase: 
Participants who are eligible for the Open-Label Phase, at the discretion of the 
investigators (taking into consideration participant’s prior documented adverse 
events, current medical status, and adherence to trial protocol), and who choose 
to participate, will be provided with the Spincare matrix and will be instructed to 
apply it once a week at most. Participant will be allowed to treat previously 
randomized wounds (treated and control wounds) and new wounds, up to a max 
of 10 individual wounds; there won’t be control nor randomized wounds. The 
wounds would be selected at the Open-Label Baseline remote visit and will need 
to meet the same wound criteria as the Randomized phase. At minimum during 
each monthly visit, participants will be required to provide digital photos taken 
with a ruler before and after the application of the Spincare matrix. Additionally, 
they will complete surveys regarding their pain and itch, offer updates on their 

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medical history, provide information about concurrent medications, and report 
any adverse events. No blood draws, wound cultures and in person visits will be 
required during the Open-Label phase.  
 
This extension phase will be 4 months long and will take place after the 
participants complete the Randomized phase. 
  
Participants who elect to participate in the Open-Label Phase will undergo 
remote visits at Open-Label Baseline (could be done during the Month 4 of the 
Randomized Phase), Open-Label Month 1, Open-Label Month 2, Open-Label 
Month 3, and Open-Label Month 4. 
 
Open-Label Baseline visit – Telehealth visit. Participant will have up to two 
weeks after the end of the Randomized Phase to enroll in the Open-Label Phase. 
At the Open-Label Baseline visit the Investigator will select up to 10 wounds from 
previously randomized (treated and control) wounds and new wounds (that meet 
the initial wound criteria). Medical history, con-medications, and adverse events 
will be reviewed. Spincare matrix will be applied on the new wounds, digital 
photographs of the wounds from before and after will be taken with a ruler by the 
caregiver/participant and sent to the research team. Participant will complete 
baseline pain and itch surveys. 
 
Open-Label Months 1, 2, 3, 4 – Investigators will arrange telehealth assessment 
visits at Open-Label Month 1, Open-Label Month 2, Open-Label Month 3 and 
Open-Label Month 4 (additional interim remote assessments if deemed 
necessary). A caregiver may travel to the participant’s home to apply the matrix 
device to the treated wounds (up to once a week if needed, they will record the 
date of application and the reason). Photographs will be taken, and investigators 
will use Telehealth to monitor for wound healing and safety reporting. At the time 
of matrix application, the caregiver will notate any wound burning sensations, 
pain, or other adverse events. Matrix will not be applied after Open-Label Week 
14 to ensure the final wound assessment at Open-Label Month 4. 
 
Open-Label Month 4 – Telehealth (End of Open-Label Phase) visit. The 
investigator will virtually assess wound healing compared to baseline 
photographs in the treated wounds. Photos of the treated wounds will be 
collected by the caregiver/participant and sent to the research team. All wound 
photos will be stored and reviewed on the REDCap. 
2.5.3 Allocation to treatment 
Intra-patient randomization and allocation of treatment is planned. Wounds will 
be matched according to wound characteristics e.g. size, severity, and location. 
Randomization will be computer generated.  
2.5.4  Unblinding 
Clinical study is not blinded. 

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2.5.5 Treatment/matrix adherence  
Treatment will be applied by investigator (initial application and reapplication on 
Day 0). Subsequent treatment will be applied by caregiver during the scheduled 
visit for Week 1, Week 2, Months 1, 2 and 3 if needed. More frequent application 
to the treatment wounds is allowed (up to once a week). 
2.5.6 Withdrawal of subjects due to non-compliance 
Subjects are allowed to withdraw at any time during the entire study period. They 
should contact the PI directly and attend an early study termination clinic visit to 
assess for adverse events and discuss ongoing treatment. 
Subjects may withdraw from study participation due to non-compliance or 
patients may choose to discontinue. Recruitment of subjects will continue until 
the minimum number of wounds is met (20 treated and 20 control wounds). 
2.5.7 Procedures to assess efficacy 
Wounds will be assessed by investigator review of photographs for achievement 
of >90% healing from baseline every two weeks for a total of 16 weeks (4 
months). Wound photos will be captured every two weeks by the subject or 
caregiving using mobile phone photographs uploaded into REDCap. Patient 
reported pain and itch surveys (Wong-Baker FACES scale and Itch Severity 
Scale (adults) / Itchy Man scale (minors) will be analyzed.  
 
The aim is to analyze all data using an intention to treat analysis method. Further 
sub-analysis will be undertaken e.g. analyze data from patients who have applied 
the Spincare matrix 80% of the expected number of times or greater.  
 
2.5.8 Procedures to assess safety 
Safety assessments for dermal tolerability such as erythema, inflammation and 
ulceration will be made by investigators. Adverse events will be documented and 
analyze. 

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2.5.9 Schedule of study visits 
 
 
Randomized Phase 
Open-Label Phase 
 
Day 0 Day 1 Week 1 Week 2 Month 1 Week 6 Month 2 Week 10 Month 3 Week 14 Month 4a 
Baselineb 
Month 1 Month 2 Month 3 Month 4 
 
Clinic Visit 
Phone Call 
Phone Call 
Medical History 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Direct Skin 
examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGA grading 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Wound selection 
and randomization 
X 
 
 
 
 
 
 
 
 
 
 
Xc 
 
 
 
 
Application of 
matrix in clinic 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Application of 
matrix at home 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
Wound culture 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
Itch and pain scores 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Caregiver survey 
 
 
 
 
 
 
 
 
X 
 
X 
 
 
 
 
 
Wound size 
measurements  
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
Photographs by 
investigator 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Photographs at 
home 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Study timeline:  
Randomized Phase: 
Day 0: in person visit; randomization of wounds with wound photography, application of matrix and monitoring of adverse events (matrix application within 30 days 
of screening).  
Day 1: in person assessment of wounds.  
Day 2 (optional): review of wounds with photographs.   
Telehealth assessment at Week 1, Week 2, Month 1, Month 2, Month 3 and Month 4 (a window of ±7 days for the monthly scheduled visits is expected).  
Participant will provide pain and itch surveys and photographs every two weeks.  
Additional visits (over secure video platform or phone calls), and reapplication of matrix by caregiver may be scheduled if deemed necessary. 
Open-Label Phase:  
Baseline Open-Label: telehealth assessment; selection of wounds and baseline wound photography, application of matrix and monitoring of adverse events.    
Telehealth assessment at Open-Label Month 1, Open-Label Month 2, Open Label Month 3 and Open-Label Month 4 (a window of ±7 days for the monthly 
scheduled visits is expected). Participant will provide pain and itch surveys and photographs at every Open-Label Month visit. Participants can reapply up to once 
a week. Additional visits (over secure video platform or phone calls), and reapplication of matrix by caregiver may be scheduled if deemed necessary. 
 
a The Baseline Open-Label visit could be done during the Randomized Phase Month 4.  
b The Baseline Open-Label visit could be done up to two weeks after the Randomized Phase Month 4 visit. 
c During the Baseline Open-Label visits the investigator will select the wounds to be treated during the Open-Label Phase. No randomization will be required.  
 

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2.6 
Study outcome evaluations 
2.6.1 Study endpoints 
 
Primary endpoint:  
Comparison of the duration of wound closure (weeks) of matrix treated wounds 
vs control wounds from baseline to Month 4. Wound photos will be captured bi-
weekly by caregivers. 
 
Secondary endpoints:  
1. Comparison of application site adverse events (burning, erythema, pain) 
between matrix treated wounds vs control wounds after application; 
2. Comparison of wound pain (Wong-Baker FACES scale) between matrix 
treated wounds vs control wounds at month 1, month 2, month 3, month 4 
(prior to matrix application);  
3. Comparison of wound itch (Itch NRS/Itchy Man scale) between matrix treated 
wounds vs control wounds at month 1, month 2, month 3, month 4 (prior to 
matrix application;  
4. 
Comparison of wounds that reach >50% healing from baseline in matrix vs 
control wounds at month 1, 2, 3, 4; 
5. 
Comparison of wounds that reach >70% healing from baseline in matrix vs 
control wounds at month 1, 2, 3, 4. 
 
 
Exploratory endpoints:  
1. Comparison of caregiver responses on wound dressing ease of use on matrix 
treated wounds vs control wounds with the Caregiver Global Impression of 
Change (CrGI); 
2. Comparison of change in wound cultures between matrix treated wounds vs 
control wounds at Month 2 and Month 4, 
 
 
2.6.2 Sample size determination 
We calculated that a sample size of 40 wounds (20 matrix-treated vs 20 
untreated) would give us 90% power to detect a difference of 8.5 vs 6 weeks 
(SD=3) of wound closure duration between untreated vs matrix treated wounds 
respectively a two-sided alpha of 0.05. This sample size calculation is based on 
our prior natural history study of 720 RDEB wounds for 6 months in 13 RDEB 
adult and pediatric participants. We anticipate that the majority of pediatric 
wounds will be the recurrent type. If the Spincare matrix reduces the duration of 
wound closure, then this clinical trial would show a novel wound healing device 
that may improve wound closure duration in difficult to heal RDEB wounds. We 
would assess the secondary endpoints to determine if a 2.5-week shorter wound 
closure is clinically meaningful and associated with wound specific decreases in 
pain and itch.  

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2.6.3 Outcome data and data analysis 
We anticipate that a higher number of wounds achieving >90 % wound closure 
would be achieved with the matrix treatment. Furthermore, we anticipate that 
patient reported wound pain and itch will be reduced with matrix treatment. This 
study would also provide pivotal data in designing future larger studies e.g. 
determination of wound type, wound location, wound size suitable for matrix 
treatment.  
3.0 
RISK ANALYSIS 
 
3.1 
Anticipated risks. 
1. 
Irritation including burning, pain and itch when the matrix treatment is 
applied to the wound bed; 
2. 
Potential allergic reaction to the matrix material.  
 
3.2 
Adverse event reporting  
3.2.1 Adverse event definitions 
Unanticipated adverse device effect (UADE): Any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated 
with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
 
Associated with the investigational device: There is a reasonable possibility 
that the adverse effect may have been caused by the investigational device. 
 
Serious adverse effect: An adverse effect is considered “serious” if, in the view 
of either the investigator or the sponsor, it results in any of the following 
outcomes:  
1. 
Death;  
2. 
A life-threatening AE; 
3. 
Inpatient hospitalization or prolongation of existing hospitalization; 
4. 
A persistent or significant disability/incapacity; 
5. 
A congenital anomaly/birth defect; 
6. 
Required intervention to prevent permanent impairment or damage. 
3.2.2  Eliciting adverse effect information 
Clinical study subjects will be questioned about adverse effects at each study 
visits including clinic visit. 
3.2.3  Recording and assessment of adverse effects 
All adverse effects (serious or non-serious) will be recorded in the subjects’ case 
report forms.  For all adverse effects, sufficient information will be pursued and/or 

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obtained to permit 1) an adequate determination of the outcome of the effect (i.e., 
whether the effect should be classified as a serious adverse effect) and; 2) an 
assessment of the casual relationship between the adverse effect and the 
investigational device. 
3.2.5 Causality and severity assessment 
The sponsor-investigator will promptly review documented adverse effects to 
determine if there is a reasonable possibility that the adverse effect was caused 
by the investigational device or other study treatments; and if the adverse effect 
meets the criteria for a serious adverse effect. 
3.2.6 Reporting adverse effects to the FDA 
For any adverse event that is determined to be a UADE, the sponsor-investigator 
will submit a safety report to the FDA.  
The completed Form FDA 3500A will be submitted to the FDA as soon as 
possible and, in no event, later than 10 working days after the sponsor-
investigator first receives notice of the adverse event. 
Subsequent to the initial submission of a completed Form FDA 3500A, the 
sponsor-investigator will submit additional information concerning the reported 
adverse effect as requested by the FDA. 
3.2.5 Reporting adverse effects to the responsible IRB 
For any adverse event determined to be a UADE, the sponsor-investigator will 
submit the completed Form FDA 3500A to the IRB as soon as possible and, in 
no event, later than 10 working days after the sponsor-investigator first receives 
notice of the adverse event. 
Other events and information that will require prompt reporting to the IRB using 
the eProtocol form include:  
(1) Unanticipated problems involving risks to participants and others (UPs) as 
defined by Stanford University’s HRPP Policy Guidance (GUI-P13, 07/22) 
(2) New Information that indicates a change to the risks or potential benefits of 
the research in terms of severity or frequency or impacts the subjects’ willingness 
to participate 
(3) Noncompliance of the investigator, study staff or others that are possible 
serious and possibly continuing 
(4) Complaint unresolved by the research team 
(5) Incarceration when in the opinion of the PD it is in the best interest of the 
participant to remain on the study 
Items 1 to 5 will be reported by the PD directly to the IRB within 10 days working 
days from when the PD learns of the event or new information. Unexpected 
deaths or life-threatening experiences related to the research will be reported to 
the IRB within 5 working days from PD learning of the event. 
 
3.3 
Withdrawal of subjects due to adverse effects 
Adverse events that are deemed serious or life-threatening will be reasons for 
withdrawal at the discretion of the investigator. Subjects will not be replaced and 
patients will be assessed as per intention to treat analysis.  

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4.0 
DESCRIPTION OF THE INVESTIGATIONAL DEVICE 
The Spincare System is comprised of a hand-held, battery-operated, portable 
device and a pre-filled, sterile, disposable, single patient, single use ampule; it 
contains a sterile, biocompatible, biodegradable polyester-based polymer 
solution. The matrix is created and applied using the help of an electrode and 
laser pointers that will guide with the appropriate distance that is required 
between the device and wound to achieve uniform matrix. No changes to the 
device are anticipated. 
5.0 
MONITORING PROCEDURES 
Monitoring of the study for compliance with the clinical protocol will be conducted 
every 4 months or when the first subject completes the trial. Monitoring will be 
done by a qualified staff of Stanford (e.g. Stanford Dermatology Project Manager 
of clinical trials with Dr. Peter Marinkovich, EB investigator not affiliated with this 
study). Dr. Marinkovich will also review the wound healing and AE results after 
the first 2 adult subjects complete the trial before any pediatric subjects will be 
enrolled. 
The sponsor-investigator will permit direct access of the study monitors and 
appropriate regulatory authorities to the study data and to the corresponding 
source data and documents to verify the accuracy of this data. 
6.0 
LABELING 
 
The labeling will contain the statement "CAUTION - Investigational Device.  
Limited by Federal (or United States) Law to Investigational Use." [§ 812.5(a))]. 
7.0 
INFORMED CONSENT 
Informed consent will be obtained in accordance with the Declaration of Helsinki, 
ICH GCP, US Code of Federal Regulations for Protection of Human Subjects (21 
CFR 50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance 
Portability and Accountability Act (HIPAA, if applicable), and local regulations. 
The Sponsor-Investigator will prepare the informed consent form and HIPAA 
authorization and provide the documents to IRB for approval.  The Sponsor-
Investigator will retain an IRB-approved copy of the Informed Consent Form in 
the study master file. A properly executed, written, informed consent will be 
obtained from each subject prior to entering the subject into the trial.  Information 
should be given in both oral and written form and subjects (or their legal 
representatives) must be given ample opportunity to inquire about details of the 
study.  A copy of the signed consent form will be given to the subject or legal 
representative of the subject and the original will be maintained with the subject’s 
records (EPIC). 

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8.0 
IRB INFORMATION 
The protocol, consent form, and other study documents including patient 
recruitment material will be reviewed and approved by Stanford IRB before the 
study is initiated.  UADEs will be reported to the IRB in accordance with the 
standard operating procedures and policies of the IRB, and the Investigator will 
keep the IRB informed as to the progress of the study.   
9.0 
ADDITIONAL RECORDS AND REPORTS   
 
9.1 
Data handling and record-keeping 
A paper Case Report Form (CRF) will be completed for each subject enrolled 
into the clinical study. The sponsor-investigator will review, approve and 
sign/date each completed CRF; the sponsor-investigator’s signature serving as 
attestation of the sponsor-investigator’s responsibility for ensuring that all clinical 
data entered on the CRF are complete, accurate and authentic.  
Subjects will have the option to complete documents and upload photos 
electronically to Stanford REDCap. Data collected at remote visits may be 
entered directly into Stanford REDCap. 
 
9.2 
Record maintenance and retention  
The sponsor-investigator will retain the study records and reports as per the local 
and federal regulatory requirements.