A Phase 3, Multi-center, Randomized, Double-Blind, Placebo Controlled Study of the Efficacy and Safety of SD-101 Cream in Patients With Epidermolysis Bullosa
Phase: PHASE3
Conditions: Epidermolysis Bullosa
Sponsor: Scioderm, Inc.

A Phase 3, Multi-center, Randomized, Double-Blind, 
Placebo Controlled Study of the Efficacy and Safety of 
SD-101 Cream in Patients with Epidermolysis Bullosa 
(ESSENCE Study) 
 
Unique Protocol ID: 
SD-005 
NCT Number: 
NCT02384460 
Date of Protocol:  
20 March 2017 
 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 1 of 50  
 
 
A Phase 3, Multi-center, Randomized, Double-Blind, Placebo Controlled Study of 
the Efficacy and Safety of SD-101 Cream in Patients with Epidermolysis Bullosa 
(ESSENCE Study) 
IND No: 107480  
Protocol No: SD-005 
Version No: 4 
Date of Protocol: May 20, 2014 
Amendment 1:  November 12, 2014 
Amendment 1.1 US:  7 May 2015 
Amendment 1.2 US:  3 August 2015 
Amendment 2:  19 September 2016 
Amendment 3:  10 March 2017 
Sponsor: Scioderm, INC. 
An Amicus Therapeutics Company 
4601 Creekstone Drive 
Suite 160 
Durham, NC  27703 
 
Author(s): 
 
 
Confidentiality Statement:   
This protocol contains information which is the property of Scioderm, INC. and therefore 
is provided to you in confidence for review by you, your staff, an applicable ethics 
committee / institutional review board and regulatory authorities. It is understood that this 
information will not be disclosed to others without written approval from Scioderm, INC. 
 
This study will be conducted in compliance with Good Clinical Practice (GCP), the 
Declaration of Helsinki (with amendments), in accordance with local legal and 
regulatory requirements and in compliance with the applicable parts of the United 
States Code of Federal Regulations. 
 
 
 
PPD

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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1. 
PROTOCOL SYNOPSIS 
PROTOCOL TITLE 
A Phase 3, Multi-center, Randomized, Double-Blind, 
Placebo Controlled Study of the Efficacy and Safety of 
SD-101 Cream in Patients with Epidermolysis Bullosa 
(ESSENCE Study) 
 
 
PROTOCOL No. 
SD-005 
 
 
VERSION No. 
4 
 
 
SPONSOR 
Scioderm, INC. 
An Amicus Therapeutics Company 
4601 Creekstone Drive 
Suite 160 
Durham, NC  27703 
 
 
INVESTIGATIONAL 
PRODUCT 
SD-101-6.0 cream administration (containing 6% 
allantoin) compared with placebo (SD-101-0.0 cream 
containing 0% allantoin).  
 
 
PHASE OF 
DEVELOPMENT 
Phase 3 
 
 
INDICATION AND 
RATIONALE 
The aim is to assess the efficacy and safety of 
SD-101-6.0 cream vs. SD-101-0.0 (placebo) in the 
treatment of patients with Epidermolysis Bullosa. 
 
 
STUDY DESIGN 
This is a Phase 3, multi-center, randomized, double-blind, 
placebo-controlled, study to assess the efficacy and safety 
of SD-101-6.0 cream vs. placebo (SD-101-0.0) on lesions 
in patients with Simplex, Recessive Dystrophic, or 
Junctional non-Herlitz Epidermolysis Bullosa. 
SD-101-6.0 cream or placebo (SD-101-0.0) will be 
applied topically, once a day to the entire body for a 
period of 90 days. Patients will be randomized on a 1:1 
basis. Patients will have 1 target wound selected at 
baseline by the Investigator. Selected target wound must 
be at least 21 days old (size 10 to 50 cm2). Photographic 
confirmation of the target wound location will be 
collected at baseline, and the picture saved from the first 
visit will be used to confirm location of the target wound 
at subsequent visits.  
The patient will return to the study site for Visit 2 
(14 days ±5 days from baseline), Visit 3 (30 days ±7 days 
from baseline), Visit 4 (60 days ±7 days from baseline), 
and Visit 5 (90 days ±7 days from baseline) to have the 

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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target wound, previously identified at baseline, 
re-assessed for the level of healing. In addition, itching, 
pain, body surface area index (BSAI), and scarring of 
healed target wound will also be assessed at each visit. 
The ARANZ SilhouetteStar™ will be used to measure 
the target wound at all visits. 
 
 
STUDY OBJECTIVE 
The primary objective is to compare the efficacy and 
safety of SD-101-6.0 vs. SD-101-0.0 (placebo) in patients 
with Simplex, Recessive Dystrophic, or Junctional 
non-Herlitz Epidermolysis Bullosa.  
 
 
STUDY EFFICACY 
ENDPOINTS 
Primary Efficacy Endpoints 
The primary efficacy endpoints for this study are:  
• Time to complete target wound closure within 
3 months   
• The proportion of patients experiencing complete 
closure of their target wound within 3 months 
 
Key Secondary Efficacy Endpoints 
The key secondary measures of efficacy include: 
• Proportion of patients experiencing complete closure 
of their target wound within 2 months 
• Proportion of patients experiencing complete closure 
of their target wound within 1 month 
• Change in lesional skin based on BSAI at Month 3, 
compared to Baseline 
•  Change in Total Body Wound Burden based on 
BSAI at Month 3, compared to Baseline 
• Change in itching assessed at Day 7, compared to 
Baseline 
• Change in pain assessed at Day 7, compared to 
Baseline 
 
Other Secondary Efficacy Endpoints 
• Change in Total Body Wound Burden based on 
BSAI at Week 2 and Months 1 and 2, compared to 
Baseline 
• Percent change from Baseline in Total Body Wound 
Burden based on BSAI at Week 2 and Months 1, 2, 
and 3 
• Change in lesional skin based on BSAI at Week 2 
and Months 1 and 2, compared to Baseline 
• Percent change in lesional skin based on BSAI at 
Week 2 and Months 1, 2, and 3, compared to 
Baseline  

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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• Presence of scarring of healed target wound at the 
visit where the complete closure is documented 
• Change in target wound characteristics (ie, 
inflammation, blistering, granulation tissue, 
erythema, exudate) at Week 2 and Months 1, 2, and 
3, compared to Baseline 
• Change in itching and pain at Days 1 to 6, Week 2, 
Months 1, 2, and 3, compared to Baseline 
• Proportion of patients experiencing target wound 
closure within Week 2 
  
 
PLANNED SAMPLE SIZE  Approximately 150 patients will be enrolled. 
 
 
PATIENT POPULATION 
Inclusion Criteria 
1. Informed Consent form signed by the patient or 
patient's legal representative; if the patient is under 
the age of 18 but capable of providing assent, signed 
assent from the patient. 
2. Patient (or caretaker) must be willing to comply with 
all protocol requirements. 
3. Diagnosis of Simplex, Recessive Dystrophic, or 
Junctional non-Herlitz EB.  
4. Patient must have 1 target wound (size 10 to 50 cm2). 
5. Patients 1 month and older.   
6. Target wound must be present for 21 days or more. 
 
 
PATIENT POPULATION 
Exclusion Criteria 
1. Patients who do not meet the entry criteria outlined 
above. 
2. Selected target wound cannot have clinical evidence 
of local infection.  
3. Use of any investigational drug within the 30 days 
before enrollment.  
4. Use of immunotherapy or cytotoxic chemotherapy 
within the 60 days before enrollment.  
5. Use of systemic or topical steroidal therapy within the 
30 days before enrollment. (Inhaled steroids and 
ophthalmic drops containing steroids are allowed) 
6. Use of systemic antibiotics within the 7 days before 
enrollment.  
7. Current or former malignancy.  
8. Arterial or venous disorder resulting in ulcerated 
lesions.  
9. Pregnancy or breastfeeding during the study. (A urine 
pregnancy test will be performed at screening and 
every 30 days until the final visit for female patients 
of childbearing potential) 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 5 of 50  
 
 
10. Females of childbearing potential who are not 
abstinent and not practicing a medically acceptable 
method of contraception.  
 
 
FORMULATION/DOSE 
SD-101 cream will be applied topically, once a day to the 
entire body for a period of 90 days. Application will 
consist of blinded SD-101-6.0 or SD-101-0.0 (placebo). 
 
 
ROUTE OF 
ADMINISTRATION 
Topical administration of SD-101-6.0 dermal cream or 
SD-101-0.0 (placebo). 
 
 
DURATION/FREQUENCY 
OF TREATMENT 
Topical application of SD-101 once daily over the entire 
body surface for 90 days. 
 
 
SAFETY ASSESSMENTS 
The safety of SD-101-0.0 and SD-101-6.0 will be 
assessed by monitoring tolerability, adverse events (AEs), 
and physical examinations. 
 
 
STATISTICAL METHODS 
Primary Efficacy Parameters: 
The primary efficacy endpoints for this study are time to 
complete target wound closure within 3 months and the 
proportion of patients experiencing complete closure of 
their target wound within 3 months. These variables will 
be compared between SD-101-6.0 and SD-101-0.0 
(placebo), and tested via a step-down procedure 
beginning with the time to complete target wound 
closure. 
 
Time to event analyses will be performed using a 
Kaplan-Meier approach, where the event is target wound 
closure measured from the date of randomization (study 
day 0) to the date of wound closure. The two treatment 
groups will be compared with respect to the two primary 
endpoints using Cox Proportional Hazards model and 
Logistic Regression, respectively. Covariates will be 
included in the Cox Proportional Hazards and Logistic 
Regression models. The approach to evaluating these and 
secondary variables will be summarized in a fully 
detailed Statistical Analysis Plan. 
 
Assumptions underlying the sample size estimation are 
that 35% of placebo patients will experience complete 
closure of their target wound at or before the 3-month 
follow-up visit and at least 60% of patients treated with 
SD-101-6.0 will experience complete closure of their 
target wound by this time (hazard ratio approximately 
2.127, assuming exponential hazards over time). Using 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 6 of 50  
 
 
these assumptions and a 1-sided overall alpha of 0.025, 
approximately 150 patients will be required (75 in each 
group) to provide approximately 86% power for time to 
complete target wound closure. There is estimated 85% 
power for proportion of patients with complete target 
wound closure.   
 
 
 
Safety Parameters: 
Adverse events will be coded using MedDRA. The 
number of events, incidence, and percentage of 
treatment-emergent AEs (TEAE) will be calculated 
overall, by system organ class (SOC), and by preferred 
term. Treatment-emergent AEs will be further 
summarized by severity and relationship to 
investigational product. Adverse events related to 
investigational product, AEs leading to withdrawal, 
serious AEs (SAEs), and deaths will be 
summarized/listed. 
 
Baseline and Month 3 physical examination results, 
together with changes during the study period, will be 
described using summary statistics. 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 7 of 50  
 
 
2. 
TABLE OF CONTENTS   
PAGE 
1. 
PROTOCOL SYNOPSIS ......................................................................................................... 2 
2. 
TABLE OF CONTENTS ......................................................................................................... 7 
3. 
LIST OF ABBREVIATIONS .................................................................................................. 9 
4. 
ADMINISTRATIVE STRUCTURE ...................................................................................... 10 
5. 
BACKGROUND INFORMATION ....................................................................................... 11 
5.1. 
Overview of Active Ingredient and Drug Product (SD-101) ..................................... 11 
5.2. 
Summary of Animal and Human Studies with SD-101 ............................................. 12 
6. 
RATIONALE FOR STUDY .................................................................................................. 13 
7. 
STUDY OBJECTIVE AND PURPOSE ................................................................................ 13 
7.1. 
Objective .................................................................................................................... 13 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS .......................................................... 14 
8.1. 
Patient Numbers ........................................................................................................ 14 
8.2. 
Inclusion Criteria ....................................................................................................... 14 
8.3. 
Exclusion Criteria ...................................................................................................... 14 
8.4. 
Withdrawal Criteria/Study Discontinuation .............................................................. 15 
8.5. 
Handling of Withdrawals........................................................................................... 15 
9. 
STUDY DESIGN ................................................................................................................... 16 
9.1. 
Primary Efficacy Endpoints ....................................................................................... 16 
9.2. 
Key Secondary Efficacy Endpoints ........................................................................... 16 
9.3. 
Other Secondary Efficacy Endpoints ........................................................................ 21 
9.4. 
Study Design ............................................................................................................. 21 
9.4.1. 
ARANZ SilhouetteStar™: ........................................................................ 22 
10. STUDY MEDICATION AND ADMINISTRATION ........................................................... 23 
10.1. 
Study Medication and Administration ....................................................................... 23 
10.2. 
Selection of Doses in the Study ................................................................................. 23 
10.3. 
Allocation to Treatment ............................................................................................. 24 
10.4. 
Duration of Patient Participation ............................................................................... 24 
10.5. 
Treatment Accountability and Compliance Checks .................................................. 24 
10.6. 
Treatment Blinding Code .......................................................................................... 24 
10.7. 
Concurrent Therapy ................................................................................................... 25 
10.7.1. 
Prohibited Medications ............................................................................. 25 
11. STUDY SCHEDULE ............................................................................................................. 26 
11.1. 
Efficacy Assessments ................................................................................................ 27 
11.2. 
Safety Assessments ................................................................................................... 27 
11.3. 
Adverse Events .......................................................................................................... 28 
11.4. 
Definitions ................................................................................................................. 28 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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11.4.1. 
Assessment of Causality ........................................................................... 30 
11.4.2. 
Adverse Event Reporting .......................................................................... 30 
11.5. 
Concomitant Medications .......................................................................................... 31 
12. STATISTICAL CONSIDERATIONS ................................................................................... 31 
12.1. 
Estimated Sample Size .............................................................................................. 31 
12.2. 
Study Populations ...................................................................................................... 32 
12.3. 
Demographics and Baseline Characteristics .............................................................. 33 
12.4. 
Statistical Methods for Efficacy Parameters.............................................................. 33 
12.5. 
Statistical Methods for Safety Parameters ................................................................. 34 
13. END OF THE STUDY ........................................................................................................... 35 
14. ETHICAL CONDUCT OF THE STUDY .............................................................................. 35 
14.1. 
Independent Ethics Committee (IEC) and Relevant Authorities ............................... 36 
14.2. 
Informed Consent ...................................................................................................... 36 
15. STUDY AND DATA MANAGEMENT ............................................................................... 37 
15.1. 
Protocol Amendments ............................................................................................... 37 
15.2. 
Monitoring ................................................................................................................. 37 
15.3. 
Quality Assurance ..................................................................................................... 37 
15.4. 
Data Recording .......................................................................................................... 37 
15.5. 
Data to be Considered as Source Data ....................................................................... 38 
15.6. 
Confidentiality ........................................................................................................... 38 
15.7. 
Retention of Study Data ............................................................................................ 39 
15.8. 
Communication and Publication of Results .............................................................. 39 
16. SIGNATURES AND AGREEMENT WITH THE PROTOCOL .......................................... 41 
17. APPENDICES ........................................................................................................................ 42 
17.1. 
Appendix 1:  EB Subtypes......................................................................................... 43 
17.2. 
Appendix 2:  Itch Man Pruritus Assessment Tool ..................................................... 45 
17.3. 
Appendix 3:  FLACC Behavioral Scale .................................................................... 46 
17.4. 
Appendix 4:  Wong-Baker FACES Pain Rating Scale .............................................. 50 
 
 

Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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3. 
LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
BSA 
Body Surface Area 
BSAI 
Body Surface Area Index 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
EB 
Epidermolysis Bullosa 
EBS 
Epidermolysis Bullosa Simplex 
ET 
Early Termination 
FDA 
Food and Drug Administration 
FLACC 
Face, Legs, Activity, Cry, Consolability 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ISC 
Independent Statistical Center 
ITT 
Intent-to-treat 
IWRS 
Interactive Web Response Services 
MEDRA 
Medical Dictionary for Regulatory Activities 
PP 
Per Protocol 
RDEB  
Recessive Dystrophic Epidermolysis Bullosa 
SAE 
Serious Adverse Event 
SD-101-0.0 
SD-101 cream containing 0% allantoin (placebo) 
SD-101-1.5 
SD-101 cream containing 1.5% allantoin 
SD-101-3.0 
SD-101 cream containing 3% allantoin  
SD-101-6.0 
SD-101 cream containing 6% allantoin 
SD-101-9.0 
SD-101 cream containing 9% allantoin 
TEAE 
Treatment Emergent Adverse Event 
U.S. 
United States 
WMA 
World Medical Association 
 

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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4. 
ADMINISTRATIVE STRUCTURE 
Medical Expert (Sponsor) 
 
1 Cedar Brook Drive 
Cranbury, NJ 08512 
 
 
1 Cedar Brook Drive 
Cranbury, NJ 08512 
 
 
Contract Research 
Organization 
Monitors 
Chiltern Inc. 
1016 West Ninth Ave. 
King of Prussia, PA 19406-1221 
 
QUINTILES 
Suite 2, Level 10, 606 St Kilda Road 
Melbourne, VIC 3004 
Australia 
 
HungaroTrial CRO 
Fehérvári út 89 95 
1119 Budapest, Hungary 
PPD
PPD

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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5. 
BACKGROUND INFORMATION 
Epidermolysis Bullosa (EB) is a rare group of inherited disorders that typically manifest 
at birth as blistering and lesion formation on the skin and, in some cases, the epithelial 
lining of other organs, in response to little or no apparent trauma. In consequence, the 
skin is extremely fragile which can result in shearing of the skin, causing a high risk of 
infection. All forms of EB are both debilitating and life threatening. In some EB 
subtypes, high mortality occurs before the age of 1 (Junctional Herlitz), and others in 
adolescences to early adulthood, typically due to infection or failure to thrive. In addition, 
children surviving into their 20’s and 30’s are also at risk for development of a virulent 
form of squamous cell carcinoma, which is in many cases fatal. 
There are no standard of care products available to treat the dermal manifestations of EB, 
and there is no approved drug for EB in either Europe or the United States. There have 
been numerous studies published on potential treatments for skin manifestations 
associated with EB, including vitamin E therapy, systemic phenytoin, topical 
nonsteroidal agents, cyproheptadine, tetracycline, and dapsone. No controlled studies 
showed clinical benefit of any therapy. Newer exploratory treatments including skin 
grafts, bioengineered skin products, and gene therapy have been unsuccessful to date. 
5.1. 
Overview of Active Ingredient and Drug Product (SD-101) 
Pharmacology of Allantoin 
The precise mechanism of action of allantoin in wound healing has not yet been defined. 
There are many animal wound and EB models, however, no product to date effective in 
any of these models has demonstrated effectiveness in humans. SD-101 was tested in the 
current appropriate wound model in EB, which is EB patients, and is the first product that 
has produced beneficial effects in healing of lesional skin, and appears to reduce the 
outbreaks of blistering. Data from the literature suggest that allantoin does not work via a 
single activity, but rather appears to affect multiple aspects of the processes involved in 
wound healing. These include reduction of inflammation, induction of growth of healthy 
tissue, stimulation of collagen as well as stimulation of granulation in ulcers, including 
tissue differentiation and epithelialization. In addition, allantoin has demonstrated 
bacteriostatic and bactericidal effects, and appears to aid in removing necrotic tissue. 
Pharmacokinetics of Allantoin 
Allantoin is a compound that is found endogenously in rats, rabbits, pigs, dogs, monkeys, 
in addition to a lower extent in humans. Allantoin is the main end product of purine 
metabolism in most mammals, and is produced from metabolism of uric acid via the 
enzyme, uricase. In rats and other mammals, uricase is present within peroxisomes of 
liver parenchymal cells. In man and great apes, uricase is not present, so that the primary 
end product of purine metabolism is uric acid. However, small amounts of allantoin are 
produced in great apes and humans via non-enzymatic conversion of uric acid. 

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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SD-101 Topical Cream 
Allantoin is the active ingredient contained within SD-101 skin cream, which is a 
commercially viable formulation with demonstrated stability of allantoin for several years 
at concentrations up to 9%. The capability to deliver the active moiety to the target in 
skin is key in topical products, since the skin is an effective barrier to penetration. In a 
series of flux studies with SD-101 containing allantoin ranging from 0.5 to 9%, 
penetration across the various skin barriers was dose-related. 
SD-101 has been developed to overcome the inherent limited solubility and stability of 
allantoin, allowing the ability to formulate allantoin at higher concentrations. In 
consequence, allantoin concentrations as high as 9% can be achieved in a topical product 
whereas the amount in existing cosmetics as an inactive excipient is typically less than 
0.2%. 
SD-101 cream is currently being developed as a new topical therapy for the treatment of 
lesional skin in patients with EB. The same product is foreseen for adult and pediatric 
patients. 
5.2. 
Summary of Animal and Human Studies with SD-101 
Toxicology studies assessing topical administration of SD-101-9.0 in multiple species 
demonstrated the lack of local or systemic effects with this active in the current 
formulation. The lack of systemic effects with allantoin in animals administered SD-101 
topically was further supported by additional safety information obtained with 
intravenous administration of allantoin in the monkey. Peak intravenous blood levels in 
the monkeys were achieved that were approximately 700 times higher than endogenous 
levels measured in published healthy human subject pharmacokinetic studies, without 
any demonstrated clinical chemistry abnormalities or organ toxicity at either the 
macroscopic or microscopic level. Additional toxicology studies with SD-101-9.0 
demonstrated that this product was non-sensitizing in the guinea pig and did not produce 
ocular irritation in the rabbit. Lastly, from examination of the excipients and the active 
ingredient, allantoin, for the ability to absorb light in the UV-A and / or UV-B ranges, 
there were no demonstrated concerns of potential phototoxicity with use of this product. 
Studies in normal volunteers with topical use of SD-101 (SD-101-0.0, SD-101-3.0, 
SD-101-6.0, and SD-101-9.0), and in EB Patients with topical usage of SD-101 
(SD-101-1.5, and SD-101-3.0) demonstrate to date that allantoin at these concentrations 
(in this formulation) has not produced any local or systemic adverse effects of concern. In 
addition, topical administration of SD-101 (SD-101-1.5) was found to be non-sensitizing 
in healthy subjects. 
An open-label study using SD-101-3.0 was previously conducted. Eight EB patients with 
a diagnosis of EB (Simplex, Recessive Dystrophic, or Junctional) based on diagnostic 
immunomapping or electron microscopy, were treated with SD-101-3.0 cream once 
applied daily to their entire skin surface, for a period up to 3 months. Application of the 

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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cream was non-irritating and did not produce any discomfort when applied to either 
unblistered areas or open lesions. The patients treated with SD-101-3.0 for three months 
showed significant improvements in the complete healing of lesions (typified by the 
results with the target wounds), clinically meaningful reductions in the extent of total skin 
surface involvement with active disease (body surface area [BSA]), and reduced pain and 
itching. Daily use of SD-101-3.0 cream in treatment up to 3 months was well tolerated by 
all patients in the study, with no related adverse events (AEs) noted. There were no 
serious AEs (SAEs) that occurred in any patient during the 3 month treatment period. In 
addition, there was good compliance on usage of the product on the entire skin surface, 
based on the soothing and non-irritating effects of the SD-101 creams. 
A Phase 2B study (SD-003) was completed with two strengths of SD-101 (containing 3% 
and 6% allantoin: identified as SD-101-3.0 and SD-101-6.0) with a matching vehicle 
control (SD-101-0.0). The primary endpoint of this study was the complete closure of the 
patient’s target chronic wound within one month. Secondary endpoints comprised effects 
on improvement in body coverage in lesional skin (including blistering), pain, and 
itching. In addition, patients from study SD-003 were offered to roll-over into an 
open-label extension study (Study SD-004) to continue treatment with SD-101-6.0 to 
collect long term safety data as well. The results of Study SD-003 support that 
SD-101-6.0 is the most efficacious concentration and provided good safety and will be 
the concentration used in this registration study (SD-005), and compared against the 
placebo group receiving SD-101-0.0. 
The design of studies SD-003 (Phase 2B) and SD-005 (Phase 3) are essentially identical, 
with differences in number of treatment arms and sample size, and minor modification of 
the minimum target wound size at study entry. Patients completing SD-005 will also be 
offered a roll-over option (Study SD-006) to receive SD-101-6.0. 
6. 
RATIONALE FOR STUDY 
SD-005 is a Phase 3 study to evaluate the efficacy and safety of SD-101-6.0 relative to a 
placebo cream in the treatment of EB patients. This confirmatory study follows the 
demonstration in a Phase 2B study that SD-101-6.0 stimulated wound closure and had an 
acceptable safety profile. 
The aim is to assess the safety and efficacy of SD-101-6.0 cream vs. placebo in the 
treatment of patients with Epidermolysis Bullosa. 
7. 
STUDY OBJECTIVE AND PURPOSE 
7.1. 
Objective 
The primary objective is to compare the efficacy and safety of SD-101-6.0 vs. 
SD-101-0.0 (placebo) in patients with Simplex, Recessive Dystrophic, or Junctional 
non-Herlitz Epidermolysis Bullosa.  

Investigational product: 
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Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
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8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Patient Numbers 
Approximately 150 patients will be enrolled at study sites worldwide. 
8.2. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for enrollment into 
the study. 
1. 
Informed Consent form signed by the patient or patient's legal representative; 
also, if the patient is under the age of 18 but capable of providing assent, signed 
assent from the patient. 
2. 
Patient (or caretaker) must be willing to comply with all protocol requirements. 
3. 
Diagnosis of Simplex, Recessive Dystrophic, or Junctional non-Herlitz EB.  
4. 
Patient must have 1 target wound (size 10 to 50 cm2). 
5. 
Patients 1 month and older.   
6. 
Target wound must be present for 21 days or more. 
8.3. 
Exclusion Criteria 
Patients with any of the following exclusion criteria will not be eligible for enrollment 
into the study. 
1. 
Patients who do not meet the entry criteria outlined above. 
2. 
Selected target wound cannot have clinical evidence of local infection.  
3. 
Use of any investigational drug within the 30 days before enrollment.  
4. 
Use of immunotherapy or cytotoxic chemotherapy within the 60 days before 
enrollment.  
5. 
Use of systemic or topical steroidal therapy within the 30 days before 
enrollment. (Inhaled steroids and ophthalmic drops containing steroids are 
allowed) 
6. 
Use of systemic antibiotics within the 7 days before enrollment.  
7. 
Current or former malignancy.  
8. 
Arterial or venous disorder resulting in ulcerated lesions.  
9. 
Pregnancy or breastfeeding during the study. (A urine pregnancy test will be 
performed at screening and every 30 days until the final visit for female 
patients of childbearing potential)  
10. Females of childbearing potential who are not abstinent and not practicing a 
medically acceptable method of contraception.  

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8.4. 
Withdrawal Criteria/Study Discontinuation 
Patients may withdraw from the study at any time without stating a reason and without 
prejudice to further treatment. The Investigator may withdraw a patient from the study 
and discontinue study treatment and assessments at any time due to safety concerns or 
concerns about the patient’s compliance with study requirements and procedures. Full 
skin examination will be performed at each visit. If SD-101 causes any significant rash 
that has not occurred previously in the patient, the Investigator should consider 
discontinuing the patient. In addition, if lesions appear to significantly worsen above the 
normal cycle seen in the patient, with use of SD-101, the Investigator should consider 
discontinuing the patient. If a patient discontinues treatment at any time after entering the 
study, the Investigator will make every effort to ensure the patient returns for all study 
visits. 
Early discontinuation of any patient who has given informed consent/assent to participate 
will be recorded including the reason for discontinuation. The primary reason for a patient 
withdrawing prematurely will be selected from the following standard categories of early 
discontinuations. 
1. Adverse Event (Adverse Reaction): Clinical events occurred or laboratory results 
are reported that in the medical judgment of the Investigator are grounds for 
discontinuation in the best interests of the patient. 
2. Withdrawal of Consent: The patient desired to withdraw from further participation 
in the study. The patient is not obligated to provide any reason for withdrawal of 
consent, but where a reason is given this will be recorded on the eCRF. 
3. Protocol Violation: The patient failed to adhere to the protocol requirements, at the 
Investigator’s discretion. 
4. Lost to Follow-Up: The patient stopped coming for visits and study personnel 
were unable to contact the patient. 
5. Other: The patient was terminated for a reason other than those listed above, such 
as, termination of study by Sponsor or enrolled in the study by error when they 
did not meet inclusion/exclusion criteria. 
8.5. 
Handling of Withdrawals 
Although a patient is not obligated to give his/her reason for withdrawing prematurely, 
the Investigator will make a reasonable effort to obtain the reason while fully respecting 
the patient’s rights. Every effort will be made to ensure the patient returns for all study 
visits, as a safety measure. If there is a medical reason for withdrawal, the patient will 
remain under the supervision of the study physician until in satisfactory health. In the 
case of withdrawal due to an AE the patient will be followed as per Section 11.3. 
Reasonable efforts will be made to contact a patient who fails to attend any follow-up 
appointments, in order to ensure that he/she is in satisfactory health.  

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9. 
STUDY DESIGN 
9.1. 
Primary Efficacy Endpoints 
The primary efficacy endpoints are: 
• The time to complete target wound closure within 3 months 
• The proportion of patients experiencing complete closure of the target wound 
within 3 months 
Complete target wound closure is defined as skin re-epithelialization without drainage.    
9.2. 
Key Secondary Efficacy Endpoints 
The key secondary efficacy endpoints are:   
• Proportion of patients experiencing complete closure of their target wound within 
2 months 
• Proportion of patients experiencing complete closure of their target wound within 
1 month 
• Change in lesional skin based on BSAI at Month 3, compared to Baseline  
This change will be measured using the following: 
Body Surface Area Index (BSAI) is a global measure of disease “spread” with 
weighting factors. The BSA affected with lesional skin will be calculated at 
baseline and at each visit to assess the total affected area before and after using 
the product.    
Definition of Lesional Skin for Assessment and Calculation of BSA Coverage 
• Consists of area(s) that contain any of the following: blisters, erosions, 
ulcerations, scabbing, bullae, and eschars, as well as areas that are 
weeping, sloughing, oozing, crusted, and denuded.   
- 
Percent of this area recorded for each defined body region 
(number from 0-100% assigned for each region) – BSA 
Note:  Coloration should not lead to misinterpretation of whether a 
lesion is active. Erythema and hyper- or hypo-pigmentation does not 
necessarily indicate that a lesion is active, and in fact can be found in 
healed or scarred skin that would not be added to BSAI calculation of 
lesional skin coverage, unless it meets the definition above. 
• Other areas categorized as skin that is either healed or scarred are not 
considered lesional skin. 

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• The BSAI will be assessed per the definition above by a study 
physician. The same study physician will perform this assessment for 
each patient visit. 

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Body Surface Area Index (BSAI) of Lesional Skin 
(Check only one box and complete the appropriate sections for each region) 
1  Ages 1 month to 7 years                                                                                               
Column 1 
Column 2 
Column 3 
Column 4 
Column 5 
Region 
Number 
Region 
Description 
Regional BSA % 
that is affected* 
Weighting 
Factor 
Total BSA %  
that is affected ** 
1 
Head / Neck 
 
x .2 
 
2 
Upper Limbs 
 
x .2 
 
3 
Trunk  
(includes groin) 
 
x .3 
 
4 
Lower Limbs 
 
x .3 
 
 
 
 
TOTAL 
 
2  Age 8 years or greater 
Column 1 
Column 2 
Column 3 
Column 4 
Column 5 
Region 
Number 
Region 
Description 
Regional BSA % 
that is affected* 
Weighting 
Factor 
Total BSA %  
that is affected ** 
1 
Head / Neck 
 
x .1 
 
2 
Upper Limbs 
 
x .2 
 
3 
Trunk  
(includes groin) 
 
x .3 
 
4 
Lower Limbs 
 
x .4 
 
 
 
 
TOTAL 
 
 
* 
For each region, enter the % of BSA that is affected with lesional skin. Score each 
region separately from 0% - 100%. 
** Multiply the value in column 3 by the factor in column 4. The Total value at the 
bottom of the table is the sum of Column 5 values for each region. 

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• Change in Total Body Wound Burden based on BSAI at Month 3, compared to 
Baseline 
Change in total body wound coverage based on BSAI estimates at each visit, 
compared to baseline will be measured using the following: 
A common measure is the Body Surface Area Index (BSAI). It is a global 
measure of disease “spread” with weighting factors. Using the same principles 
that underlie the BSAI estimates of lesional skin, the percentage of the total BSA 
affected by open wounds will be calculated at baseline and at each visit to assess 
the total wound area before and after using the product.    
Calculation of Total Body Wound Burden  
• The BSAI of wounds will be assessed by a study physician. The same 
study physician will perform this assessment for each patient visit. 
• A wound is defined as an open area on the skin (epidermal covering is 
disrupted). 

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Body Surface Area Index (BSAI) of Total Body Wound Burden 
(Check only one box and complete the appropriate sections for each region) 
1  Ages 1 month to 7 years                                                                                               
Column 1 
Column 2 
Column 3 
Column 4 
Column 5 
Region 
Number 
Region 
Description 
Regional BSA % 
that is affected* 
Weighting 
Factor 
Total BSA %  
that is affected ** 
1 
Head / Neck 
 
x .2 
 
2 
Upper Limbs 
 
x .2 
 
3 
Trunk  
(includes groin) 
 
x .3 
 
4 
Lower Limbs 
 
x .3 
 
 
 
 
TOTAL 
 
2  Age 8 years or greater 
Column 1 
Column 2 
Column 3 
Column 4 
Column 5 
Region 
Number 
Region 
Description 
Regional BSA % 
that is affected* 
Weighting 
Factor 
Total BSA %  
that is affected ** 
1 
Head / Neck 
 
x .1 
 
2 
Upper Limbs 
 
x .2 
 
3 
Trunk  
(includes groin) 
 
x .3 
 
4 
Lower Limbs 
 
x .4 
 
 
 
 
TOTAL 
 
 
* 
For each region, enter the % of BSA that is affected with open wounds. Score each 
region separately from 0% - 100%. 
** Multiply the value in column 3 by the factor in column 4. The Total value at the 
bottom of the table is the sum of Column 5 values for each region. 

Investigational product: 
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• Change in itching assessed at Day 7, compared to Baseline 
Change in itching assessed at Week 1 (Day 7), compared to baseline will be 
measured using the “Itch Man Pruritus Assessment Tool”. For patients 1 month to 
5 years of age itching will be assessed using caretaker’s response and patients 
6 years of age and older will self-report their itching assessments. See 
Section 17.2, Appendix 2 for the Itch Man Pruritus Assessment Tool. 
• Change in pain assessed at Day 7, compared to Baseline 
Change in pain assessed at Week 1 (Day 7), compared to baseline will be 
measured using the “FLACC scale” for patients 1 month to 3 years of age and for 
patients 4 years of age and older the “Wong Faces Pain Scale” will be utilized. 
See Section 17.3, Appendix 3 for the FLACC Behavioral Scale and Section 17.4, 
Appendix 4 for the Wong Faces Pain Scale. 
9.3. 
Other Secondary Efficacy Endpoints 
• Change in Total Body Wound Burden based on BSAI at Week 2 and Months 1 
and 2, compared to Baseline 
• Percent change from Baseline in Total Body Wound Burden based on BSAI at 
Week 2 and Months 1, 2, and 3 
• Change in lesional skin based on BSAI at Week 2 and Months 1 and 2, compared 
to Baseline 
• Percent change in lesional skin based on BSAI at Week 2 and Months 1, 2, and 3, 
compared to Baseline 
• Presence of scarring of healed target wound at the visit where the complete 
closure is documented 
• Change in target wound characteristics (ie, inflammation, blistering, granulation 
tissue, erythema, exudate) at Week 2 and Months 1, 2, and 3, compared to 
Baseline 
• Change in itching and pain at Days 1 to 6, Week 2, and Months 1, 2, and 3, 
compared to Baseline 
• Proportion of patients experiencing target wound closure within Week 2 
9.4. 
Study Design 
This is a Phase 3, multi-center, randomized, double-blind, placebo controlled, study to 
assess the efficacy and safety of SD-101-6.0 cream vs. SD-101-0.0 (placebo) in the 
treatment of lesions in approximately 150 patients with Simplex, Recessive Dystrophic, 
or Junctional non-Herlitz Epidermolysis Bullosa. 
Patients will be randomized on a 1:1 basis to either SD-101-6.0 cream or placebo 
(SD-101-0.0). SD-101-6.0 or placebo will be applied topically, once a day to the entire 
body for a period of 90 days.   

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Patients will have 1 target wound selected at baseline by the Investigator. The 
Investigator should identify a target wound per the ARANZ SilhouetteStar™ system 
manuals and training provided. At screening, multiple wounds on the subject can be 
assessed against study inclusion/exclusion criteria. The selected target wound must be at 
least 21 days old (size 10 to 50 cm2). Photographic confirmation of the target wound 
location will be collected at baseline, and the picture saved from the first visit will be 
used to confirm location of the target wound at subsequent visits. Once the target wound 
is identified, it should be followed during the subsequent study visits 2, 3, 4 and 5. It 
should be ensured that only 1 wound  is selected for the study and followed within the 
ARANZ system. 
Patients who have an eligible target wound and meet all other inclusion/exclusion criteria 
will be randomized. Patients who screen fail may be rescreened. The first dose of 
treatment will be administered during the office visit. Patients randomized will initially 
be given one-month supply of study medication. 
The patient will return to the study site for Visit 2 (14 days ±5 days from baseline), 
Visit 3 (30 days ±7 days from baseline), Visit 4 (60 days ±7 days from baseline), and 
Visit 5 (90 days ±7 days from baseline) to have the target wound, previously identified at 
baseline, re-assessed for the level of healing. In addition, itching, pain, body surface area 
index (BSAI), and scarring of healed target wound will also be assessed at each visit. The 
ARANZ SilhouetteStar™ will be used to measure the target wound area at all visits.  
All females of childbearing potential must have a negative urine pregnancy test prior to 
enrolling in the study and must agree to use some form of birth control or agree to remain 
abstinent until the study is completed. In addition, a urine pregnancy test will be 
performed at the screening visit and every 30 days until the final visit. 
Safety assessments will include monitoring of tolerability, AEs, and physical 
examinations.   
Patients who complete the study will be eligible to enroll into an open-label study 
(SD-006).   
9.4.1. 
ARANZ SilhouetteStar™: 
The ARANZ measurement device is a portable device that easily allows capture of 
information about a patient’s target wound. This information is analyzed, managed, and 
stored in a database on a secure device. Information captured includes photographic 
images, quantitative measures and other target wound assessment data input to the device 
by the clinician, all obtained with no contact with the patient’s skin. ARANZ then builds 
that into an electronic record for printing and archiving. Information about the target 
wound’s measurement history is available on this system so that the serial progression of 
the target wound status can also be calculated and presented.   

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The ARANZ measurement device has FDA 510(k) approval and is not being assessed for 
safety and efficacy in this study. The device is only being utilized to perform 
measurements. 
 
 
Figure 9-1 
ARANZ SilhouetteStar™ 
 
10. 
STUDY MEDICATION AND ADMINISTRATION 
10.1. 
Study Medication and Administration 
SD-101-6.0 or SD-101-0.0 (placebo) creams will be supplied in 8 ounce plastic tubes, to 
be reclosed after use and stored at room temperature. 
SD-101-6.0 or SD-101-0.0 will be applied topically once a day to the entire body for a 
period of 90 days. The first dose of study treatment will be administered during the first 
study visit upon randomization and after completion of the physical examination, 
baseline BSAI, itching, and pain assessments. 
The patient diary will be returned at visits 3, 4 and 5 to evaluate compliance.   
Additional information on the composition of the SD-101 dermal cream is contained in 
the SD-101 Investigator’s Brochure. 
10.2. 
Selection of Doses in the Study 
SD-101-6.0 dermal cream or SD-101-0.0 (placebo) will be applied topically once a day to 
the entire body.  

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10.3. 
Allocation to Treatment 
Approximately 150 patients will be randomized using Interactive Web Response System 
(IWRS) to 1 of 2 dose-concentration groups: SD-101-0.0 (placebo) or SD-101-6.0.  
10.4. 
Duration of Patient Participation 
It is anticipated that each eligible patient will participate in the trial for approximately 
90 days.  
Patients who successfully complete the study will be eligible to enroll into an open-label 
study (SD-006).   
10.5. 
Treatment Accountability and Compliance Checks 
The Sponsor or Designee will be responsible for performing drug accountability for the 
dermal cream. The medication provided for this study is for use only as directed in the 
protocol. It is the Investigator/Institution’s responsibility to establish a system for 
handling study treatments, including investigational medicinal products, so as to ensure 
that: 
• Deliveries of such products are correctly received by a responsible person 
• Such deliveries are recorded 
• Study treatments are handled and stored safely and properly as stated on the label 
• Study treatments are only dispensed to study patients in accordance with the 
protocol 
• Any unused products may be destroyed by the site or returned to the 
investigational product distribution center for destruction. 
At the end of the study, it must be possible to reconcile delivery records with records of 
usage and destroyed stock. Records of usage should include the identification of the 
person to whom the study treatment was dispensed, the quantity of the study cream and 
date of dispensing. This record is in addition to any drug accountability information 
recorded on the electronic case report form (eCRF). Any discrepancies must be 
accounted for on the appropriate forms. Certificates of initial and any subsequent 
deliveries and destruction must be signed, preferably by the Investigator or a pharmacist, 
and copies retained in the Investigator Site File. 
10.6. 
Treatment Blinding Code 
The medical care of the trial subjects includes medical decisions such as whether to start 
or stop treatment or institute alternative treatment if required. In emergency situations, 
the Investigator may need to break the treatment code immediately, or as quickly as 
possible if he/she finds it is in the best interest of the trial subject. If the blinding is 

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prematurely broken, it is the responsibility of the Investigator to promptly document and 
explain any unblinding to the Sponsor. 
10.7. 
Concurrent Therapy 
Administration of the following medications is acceptable and will not result in the 
withdrawal of patient. 
• Oral and topical antihistamines 
• Topical antibiotics  
• Systemic antibiotics  
• Inhaled steroids and ophthalmic drops containing steroids 
• Non-steroidal anti-inflammatory drugs (NSAIDs)  
• Limited steroid use is acceptable for planned medical procedures, including but 
not limited to, esophageal dilatation 
• Morphine or other narcotic pain relievers 
• Vitamins 
Medications considered necessary for the patient’s welfare (intercurrent illness or AEs) 
may be given at the discretion of the Investigator. The Investigator should consider the 
necessity of any therapy before prescribing it to the patient. Subjects must be instructed 
not to take any medications without prior consultation with the Investigator, as feasible. 
The administration of all such medication / therapy must be recorded in the appropriate 
section of the eCRF and will be assessed at each visit.  
10.7.1. 
Prohibited Medications 
The use of immunosuppressive agents or corticosteroids (oral, rectal, intravenous, 
and topical) are prohibited (however, limited steroid use is acceptable for planned 
medical procedures, including but not limited to, esophageal dilatation). Use of 
prohibited medications during the trial may result in the withdrawal of the subject based 
on the assessment by the Investigator and medical monitor.  

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11. 
STUDY SCHEDULE 
Procedure 
Visit 
1  
Screening/ 
Baseline 
2 
Week 2 
3 
Month 1 
4 
Month 2 
5 
Month 3  
Final Visit/  
ET 
Study Day  
(-7) to (0) 
14 (±5d) 
30 (±7d) 
60 (±7d) 
90 (±7d) 
Informed consent /assent signed 
X 
 
 
 
 
Inclusion/Exclusion assessment  
X 
 
 
 
 
Demographic, medical and medication 
history 
X 
 
 
 
 
Physical examination a 
X 
 
 
 
X 
Height, weight, and temperature 
X 
 
 
 
X 
Identify and document location of one 
target wound.  
X 
 
 
 
 
Assess target wound with ARANZ. If 
healed, assess for scarring 
X 
X 
X 
X 
X 
Assess overall itching c 
X 
X 
X 
X 
X 
Assess overall pain with age-
appropriate scale c 
X 
X 
X 
X 
X 
Assess BSA of lesional skin 
X 
X 
X 
X 
X 
Assess BSA of wound burden 
X 
X 
X 
X 
X 
Urine pregnancy test (females only) b 
X 
 
X 
X 
X 
Administer first dose of SD-101 cream 
X 
 
 
 
 
Dispense pain and itching scales for 
completion during next 7 days of at 
home treatment c 
X 
 
 
 
 
Collect and review pain and itching 
scales completed at home c 
 
X 
 
 
 
Dispense diaries 
X 
 
X 
X 
 
Collect and review diaries 
 
 
X 
X 
X 
Dispense SD-101 cream 
X 
 
X 
X 
 
Collect SD-101 cream for the purpose 
of drug accountability 
 
 
X 
X 
 
Collect all SD-101 cream for final 
drug accountability 
 
 
 
 
X 
Monitor adverse events  
 
X 
X 
X 
X 
Monitor use of concomitant 
medications 
X 
X 
X 
X 
X 
a. A complete physical examination will be performed at Visits 1 and 5.  
b. Urine pregnancy test will be performed at Visits 1, 3, 4, and 5. 
c. Itching will be assessed using the “Itch Man Pruritus Assessment Tool”. For patients up to 5 years of age itching 
will be assessed using caretaker’s response and patients 6 years of age and older will self-report their itching 
assessments. Pain will be assessed using the “FLACC scale” for patients up to 3 years of age and for patients 
4 years of age and older the “Wong Faces Pain Scale” will be utilized. 

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11.1. 
Efficacy Assessments 
Time to complete target wound closure within 3 months and the proportion of patients 
experiencing complete target wound closure within 3 months are the primary measures of 
efficacy.  
The key secondary measures of efficacy include: 
• Proportion of patients experiencing complete closure of their target wound within 
2 months 
• Proportion of patients experiencing complete closure of their target wound within 
1 month 
• Change in lesional skin based on BSAI  at Month 3, compared to Baseline 
• Change in Total Body Wound Burden based on BSAI at Month 3, compared to 
Baseline 
• Change in itching assessed at Week 1 (Day 7), compared to Baseline 
• Change in pain assessed at Week 1 (Day 7), compared to Baseline 
Other secondary measures of efficacy include: 
• Change in Total Body Wound Burden based on BSAI at Week 2 and Months 1 and 
2, compared to Baseline 
• Percent change from Baseline in Total Body Wound Burden based on BSAI at 
Week 2 and Months 1, 2, and 3 
• Change in lesional skin based on BSAI at Week 2 and Months 1 and 2, compared to 
Baseline 
• Percent change in lesional skin based on BSAI at Week 2 and Months 1, 2, and 3, 
compared to Baseline 
• Presence of scarring of healed target wound at the visit where the complete closure 
is documented 
• Change in target wound characteristics (ie, inflammation, blistering, granulation 
tissue, erythema, exudate) at Week 2 and Months 1, 2, and 3, compared to Baseline 
• Change in itching and pain at Days 1 to 6, Week 2, and Months 1, 2, and 3, 
compared to Baseline 
• Proportion of patients experiencing target wound closure within Week 2 
11.2. 
Safety Assessments 
The safety of SD-101-0.0 and SD-101-6.0 dermal creams, applied daily to the entire skin 
surface, will be assessed by monitoring tolerability, AEs, and physical examinations. 

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For timing of individual measurements, refer to Section 11, Study Schedule. 
Physical Examination Including Height/Length, Weight, and Temperature 
Physical examinations will be done by a physician. The following sites will be examined: 
head, eyes, ears, nose, throat, neck, chest, lungs, heart, abdomen, skin, and lymph nodes; 
and the following systems will be assessed: musculoskeletal and neurological. Weight, 
height/length, and temperature will be recorded. 
Urinalysis 
Urine pregnancy tests will be performed for female patients of child bearing potential 
(sensitivity at least 25 mIU/mL) at Visits 1, 3, 4, and 5. 
11.3. 
Adverse Events 
Adverse events (AEs) may be volunteered spontaneously by the patient or discovered as 
a result of general, non-leading questioning. All AEs should be recorded in the eCRF. 
Adverse events will be collected after signing the informed consent/assent through Visit 5 
and these AEs will be followed up to 30 days after the last dose of study drug has been 
administered. This follow up is not required for subjects who enter the SD-006 study.  
In the case of withdrawal due to an AE/SAE, the patient will be followed until resolution 
of the AE, or until in the opinion of the Investigator, the event has stabilized, or the 
Investigator does not expect any further improvement or worsening of the subject’s 
condition, and the patient is referred to their primary physician for appropriate 
management of the ongoing event. Reasonable efforts will be made to contact a patient 
who fails to attend any follow-up appointments, in order to ensure that he/she is in 
satisfactory health. 
11.4. 
Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a patient, administered a medicinal product and 
which does not necessarily have to have a causal relationship with this treatment. An AE 
can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product. AEs may 
include the onset of new illness and the exacerbation of pre-existing conditions. 
The routine evolution of the disease condition under treatment according to the protocol 
will be evaluated as part of the disease symptoms assessments. Changes in the disease 
condition may not qualify as AEs. However, if there is a clinically relevant worsening of 
a sign or symptom of the condition under treatment and the outcome fulfills the definition 
of an AE, it must be reported as directed in the protocol. 

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Adverse Drug Reaction (ADR) 
All events considered to be noxious and unintended responses to a medicinal product 
related to any dose should be considered adverse drug reactions. The phrase “responses to 
a medicinal product” means that a causal relationship between a medicinal product and 
an AE is at least a reasonable possibility, ie, the relationship cannot be ruled out. 
Serious Adverse Event (SAE) 
An AE that at any dose: 
• Results in death 
• Is life-threatening (ie, the patient was at risk of death at the time of the event; it 
does not refer to an event which hypothetically might have caused death if it was 
more severe) 
• Results in hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly / birth defect 
• Is considered to be an important medical event 
Based upon medical and scientific judgment, important medical events that may not be 
immediately life-threatening, or result in death or hospitalization, but may jeopardize the 
patient or may require intervention to prevent one of the other outcomes listed in the 
definition above may be considered an SAE. 
Hospitalizations are defined as initial or prolonged admissions that include an overnight 
stay. Hospitalization or prolonged hospitalization for technical, practical, or social 
reasons, in the absence of an AE is not an SAE. 
Pregnancy 
Pregnancy itself is not considered an AE. Pregnancies will be reported and documented 
on a separate pregnancy report form provided to the sites. However, any pregnancy 
complication, spontaneous or elective abortion, still birth, neonatal death, or congenital 
anomaly will be recorded as an SAE. 
Unexpected Adverse Drug Reaction 
An adverse reaction, the nature or severity of which is not consistent with applicable 
product information (eg, Investigators Brochure for an unapproved investigational 
medicinal product). 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A SUSAR is an SAE that is suspected to be related to the administered medicinal product 
and the nature or severity of which is not consistent with applicable product information. 

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11.4.1. 
Assessment of Causality 
Severity 
The severity (intensity) of each AE will be classified by the Investigator as: 
• Mild: 
Awareness of sign of symptom, but easily tolerated 
• Moderate: Sign or symptom causes discomfort, but does not interfere with 
normal activities 
• Severe: 
Sign or symptom of sufficient intensity to interfere with normal 
activities 
Causality 
The likely relationship of each AE to the medicinal product will be assessed by the 
Investigator and reported according to the definitions below: 
• Unrelated  ○ 
Event occurred before dosing or 
○ 
Event or intercurrent illness due wholly to factors other than 
drug treatment. 
• Possibly 
○ 
Reasonable temporal relationship with drug treatment. 
○ 
Event could be explained by patient’s clinical state or other 
factors. 
• Probably 
○ 
Reasonable temporal relationship with drug treatment. 
○ 
Likely to be known reaction to agent or chemical group, or 
predicted by known pharmacology. 
○ 
Event cannot easily be explained by patient’s clinical state or 
other factors. 
• Definitely 
○ 
Distinct temporal relationship with drug treatment. 
○ 
Known reaction to agent or chemical group, or predicted by 
known pharmacology. 
○ 
Event cannot be explained by patient’s clinical state or other 
factors. 
11.4.2. 
Adverse Event Reporting 
The Investigator shall immediately report any serious adverse event that occurs to the 
Sponsor. Immediate reporting allows the Sponsor to take the appropriate measures to 
address potential new risks in a clinical trial. Therefore, the immediate report should be 
made by the Investigator within a very short period of time and under no circumstances 
should this exceed 24 hours following knowledge of the serious adverse event 
The Sponsor is required to expedite the reporting to all concerned Investigators / 
Institutions, to the Institutional Review Boards (IRBs), where required, and to the 
regulatory authorities of all ADRs that are serious unexpected and reasonably associated 

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with the investigational product as assessed by the Sponsor. Such expedited reports 
should comply with the applicable regulatory requirements and with the ICH Guideline 
for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting 
(E2A). The Sponsor should submit to the regulatory authorities all safety updates and 
periodic reports, as required by applicable regulatory requirements. 
The Sponsor will submit to the regulatory authorities all safety updates and periodic 
reports, as required by applicable regulatory requirements. 
11.5. 
Concomitant Medications 
All concomitant medications will be recorded.   
12. 
STATISTICAL CONSIDERATIONS 
This section outlines the general statistical considerations for the study. Details regarding 
study statistics are described in the Statistical Analysis Plan. 
12.1. 
Estimated Sample Size 
The primary efficacy endpoints for this study are the time to complete target wound 
closure within 3 months and the proportion of patients experiencing complete closure of 
their target wound within 3 months. These variables will be compared between 
SD-101-6.0 and SD-101-0.0 (placebo) via step-down testing to control type 1 error at 
overall level of 0.025 1-sided. Time to complete target wound closure is the first endpoint 
to be tested. Complete target wound closure is defined as skin re-epithelialization without 
drainage. The two treatment groups will be compared with respect to the primary 
endpoints using Cox Proportional Hazards model and Logistic Regression, respectively. 
Both models will be adjusted for covariates. For time to complete target wound closure, 
which is the first primary endpoint to be tested, the data will be right censored at 
3 months or at the time of withdrawal from the study. If the first primary endpoint is 
significant, then the successful evidence of efficacy of SD-101-6.0 will be concluded and 
testing will proceed further to the second primary endpoint and then to the key secondary 
endpoints.  
For the second primary endpoint and for relevant secondary endpoints, missing data will 
be imputed using Multiple Imputation (MI) method with the Missing At Random (MAR) 
assumption. Details will be described in the Statistical Analysis Plan. 
To assess the robustness of the missing data, imputation methodology sensitivity analyses 
will also be conducted including an approach that subjects with missing wound healing 
data within month 3 will be considered ‘failures’ for the wound healing rate. Details will 
be provided in the Statistical Analysis Plan. 
Assumptions underlying the sample size estimation are that 35% of placebo patients will 
experience complete closure of their target wound at or before the 3-month follow-up 

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visit and at least 60% of patients treated with SD-101-6.0 will experience complete 
closure of their target wound by this time (hazard ratio approximately 2.127, assuming 
exponential hazards over time). Note that ALL wounds are open at baseline; hence, the 
survival endpoint is an open wound. It is expected that fewer wounds will stay open on 
test treatment than on placebo; hence, the expected proportions of open wounds at 
3 months are 65% on placebo and 40% on test treatment, which corresponds to a 
HR=2.127. These yield the 35% expected wound closures for placebo (35% = 100% - 
65% surviving open), and 60% for SD-101-6.0 (60% = 100% - 40% surviving open). 
Using these assumptions and a 1-sided overall alpha of 0.025, approximately 150 patients 
will be required (75 in each group) to provide at least 86% power for time to complete 
target wound closure. There is estimated 85% power for the proportion of patients with 
complete target wound closure.  
 
Therefore, approximately 150 patients are to be enrolled.  
12.2. 
Study Populations 
Analysis Populations 
The Intent-to-Treat (ITT) population will be used for all efficacy analyses. The Safety 
population (SAF) will be used for all safety analyses. The Per Protocol (PP) population 
will be used for supportive analyses of the efficacy endpoints. 
If the SAF and ITT populations are identical, then the safety analyses will be performed 
using the ITT population only. 
Intent-to-Treat (ITT) Population 
The intent-to-treat (ITT) population will be defined as all patients who have been 
randomized to study treatment. These patients will be analyzed according to the assigned 
treatment. 
Safety (SAF) Population 
The Safety (SAF) population is defined as all randomized patients who applied/were 
administered the study medication at least once. These patients will be analyzed 
according to the treatment actually received. 
Per Protocol (PP) Population  
The per protocol (PP) population will be defined as the ITT patients who have no major 
protocol deviations and have target wound data at baseline and from ≥1 post-baseline 
assessment.  
Major protocol deviations include but are not limited to: 
1. Entry criterion deviations that impact primary endpoint analyses 

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2. Non-compliance to study drug (as defined by compliance to study drug <70% as 
per patient diary) 
3. Administrative dispensing errors 
A final list of major protocol deviation criteria and patients who have any major protocol 
deviations will be documented before  final database lock. A listing will also be created. 
12.3. 
Demographics and Baseline Characteristics 
Descriptive summaries of demographic and baseline characteristics will be presented for 
the ITT Population and Safety Populations by treatment group.  
Continuous variables such as patient age, weight, height/length and temperature, will be 
summarized using number of observations, mean, standard deviation, median, minimum, 
and maximum values. Categorical variables such as patient sex and race will be 
summarized using number of observations and percentages for each category.   
Medical history and concomitant medications will be summarized using the number of 
observations and percentages of patients reporting each category. 
12.4. 
Statistical Methods for Efficacy Parameters 
Primary Efficacy Parameters: 
The primary efficacy endpoints for this study are the difference between SD-101-6.0 and 
SD-101-0.0 (placebo) in: 
• The time to complete target wound closure within 3 months  
• The proportion of patients experiencing complete closure of their target wound 
within 3 months  
The two treatment groups will be compared with respect to the primary endpoint using 
Cox Proportional hazards model and Logistic Regression, respectively. Covariates in 
both models are: baseline target wound size, target wound age, and EB type. The 
proportional hazards assumption will be assessed and if important departure is observed, 
then the stratified log rank test will be used. For the time to target wound closure 
analysis, data will be right censored at 3 months or the time of withdrawal from the study. 
For the proportion of patients with complete target wound closure, missing data will be 
imputed using the Multiple Imputation (MI) method with the Missing At Random (MAR) 
assumption.  
To assess the robustness of the missing data, imputation methodology sensitivity analyses 
will also be conducted including an approach that subjects with missing wound healing 
data within month 3 will be considered ‘failures’ for the wound healing rate. Details will 
be provided in the Statistical Analysis Plan. 

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Key Efficacy Endpoints: 
Key secondary efficacy parameters include the following: 
• Proportion of patients experiencing complete closure of their target wound within 
2 months 
• Proportion of patients experiencing complete closure of their target wound within 
1 month 
• Change in lesional skin based on BSAI  at Month 3, compared to Baseline 
• Change in Total Body Wound Burden based on BSAI at Month 3, compared to 
Baseline 
• Change in itching assessed at Day 7, compared to Baseline 
• Change in pain assessed at Day 7, compared to Baseline 
Other Secondary Efficacy Endpoints: 
Other secondary efficacy endpoints include the following: 
• Change in Total Body Wound Burden based on BSAI at Week 2 and Months 1 and 
2, compared to Baseline 
• Percent change from Baseline in Total Body Wound Burden based on BSAI at 
Week 2 and Months 1, 2, and 3 
• Change in lesional skin based on BSAI at Week 2 and Months 1 and 2, compared to 
Baseline 
• Percent change in lesional skin based on BSAI at Week 2 and Months 1, 2, and 3, 
compared to Baseline   
• Presence of scarring of healed target wound at the visit where the complete closure 
is documented 
• Change in target wound characteristics (ie, inflammation, blistering, granulation 
tissue, erythema, exudate) at Week 2 and Months 1, 2, and 3, compared to Baseline 
• Change in itching and pain at Days 1 to 6, Week 2, and Months 1, 2, and 3, 
compared to Baseline 
• Proportion of patients experiencing target wound closure within Week 2 
A detailed Statistical Analysis Plan will be completed prior to database lock. 
12.5. 
Statistical Methods for Safety Parameters 
Adverse events will be coded using MedDRA. The number of events, incidence, and 
percentage of treatment-emergent AEs (TEAE) will be calculated overall, by system 

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organ class (SOC), and by preferred term. Treatment-emergent AEs will be further 
summarized by severity and relationship to investigational product. Adverse events 
related to investigational product, AEs leading to withdrawal, SAEs, and deaths will be 
summarized. 
Baseline and Month 3 physical examination results, together with changes during the 
study period, will be described using summary statistics. 
13. 
END OF THE STUDY 
The end of the study will be defined as the last patient’s last visit. 
The study will be terminated early if, in the opinion of the Sponsor, Investigators, or 
IRBs, an unacceptable risk to the safety and welfare of patients is posed by the 
continuation of the study in light of review of the key unexpected AEs occurring during 
the trial. 
Within the provisions of informed consent / assent and good clinical judgment with 
respect to safety, every attempt will be made to have patients complete the study. 
The following reasons are grounds to terminate a patient’s participation in the study: 
1. Patient develops intolerable adverse effects, including but not limited to: 
• Severe and widespread dermatological reactions beyond the area of 
application. 
• Severe local reactions requiring systemic steroid therapy. 
2. Any patient who becomes significantly noncompliant with study drug 
administration, study procedures, or study requirements should be withdrawn 
from study treatment when the circumstances increase risk to the subject or 
substantially compromise the interpretation of study results. 
3. The patient’s health would be jeopardized by continued participation. 
4. Investigator judgment deems it appropriate. 
5. The patient wishes to withdraw for any reason. 
6. The Sponsor elects to end the study, or any portion thereof, for any reason. 
14. 
ETHICAL CONDUCT OF THE STUDY 
This study will be conducted in accordance with ethical principles founded in the 
Declaration of Helsinki and in compliance with the protocol, International Conference on 
Harmonisation [ICH] GCP, and applicable local legal and regulatory requirements 
(including ICH guidelines, the European Union Clinical Trials Directive 2001/20/EC, the 
GCP Directive 2005/28/EC, the requirements of local IEC/IRB, and the US Code of 
Federal Regulations, Title 21 CFR Part 50, 54, 56 and 312). 

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14.1. 
Independent Ethics Committee (IEC) and Relevant Authorities 
This protocol and the subject informed consent form (ICF) must be reviewed and 
approved by an institutional review board (IRB)/independent ethics committee (IEC) 
complying with the requirements of 21 CFR Part 56 and local regulatory requirements 
before subject enrollment at each site. The letter (or certificate of approval) from the 
IRB/IEC must be received by the Sponsor or its designee prior to delivery of clinical 
supplies. The IRB/IEC will be notified of any SAE or suspected unexpected serious 
adverse reaction in accordance with local regulatory requirements. 
Any changes to the study design will be formally documented in protocol amendments 
and approved by the IRB prior to implementation, except in the case of changes made to 
protect patient safety, which will be implemented immediately. 
Clinical Trial Authorization will be obtained prior to initiation of the study from the US 
Food and Drug Administration. 
14.2. 
Informed Consent  
The principles of informed consent in the Declaration of Helsinki, in ICH Good Clinical 
Practice and in US 21 CFR Part 50 (Protection of Human Subjects) will be implemented 
before any protocol-specified procedures or interventions are carried out. 
A signed informed consent / assent form (ICF) shall be obtained from each patient and/or 
legal guardian if under 18 years of age prior to entering the study. The Investigator is 
responsible for obtaining written informed consent / assent from the patient and or legal 
guardian after adequate explanation of the aims, methods, anticipated benefits, and 
potential hazards of the study and before any protocol specific screening procedures or 
any study medications are administered. Information should be given in both oral and 
written form whenever possible and deemed appropriate by the IRB. Patients will also be 
asked to consent to allow the Sponsor, Sponsor representative or external regulatory 
auditor to review their medical records to confirm compliance with GCP. 
The acquisition of informed consent / assent should be documented in the patient’s 
medical record and the ICF should be signed and personally dated by the patient and or 
legal guardian and by the person who conducted the informed consent / assent discussion 
(not necessarily by the Investigator). The original signed ICF should be retained in the 
Investigator Site File and a copy of the signed consent should be provided to the patient 
prior to participation in the trial. 
The patient will be informed that they may withdraw from the study at any time without 
prejudice to further treatment. They will receive all information that is required by local 
regulations and ICH guidelines. 

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15. 
STUDY AND DATA MANAGEMENT 
15.1. 
Protocol Amendments 
No amendments to the protocol will be implemented prior to agreement from the 
Sponsor, and prior to approval from appropriate authorities. 
15.2. 
Monitoring 
The study monitor will review the progress of the study on a regular basis to ensure 
adequate and accurate data collections. Monitoring site visits to review eCRFs, patient 
case notes, patient diaries, administrative documentation including the Investigator Site 
File and frequent telephone communications with site will be performed throughout the 
study. 
At each study monitoring visit the Investigator will make available all records pertaining 
to the study. To allow sufficient time to assemble documentation for the study monitor, 
monitoring visits will be confirmed in advance of planned visits. 
All relevant communications, between the Sponsor, designated study representative, and 
Investigator should be documented for the study file. 
15.3. 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, the 
Investigator[s]/Institution[s] will permit study-related audits, IRB/IEC review, and 
regulatory inspection[s], providing direct access to source data/documents. 
The Sponsor or Sponsor representative or external regulatory agency may at any time 
during or after completion of the study conduct a Good Clinical Practice (GCP) audit. 
Prior notice will be given to each site selected for audit in advance of a planned GCP 
audit. 
15.4. 
Data Recording 
The Investigator has the responsibility for ensuring that all source documents (ie, study 
and/or medical records and patient’s diary) are completed and maintained according to 
the study protocol, and are available at the site. 
Patients/Caretaker will utilize the diaries to record the following: 
• Date cream is applied 
• Rate overall itching each day, at a similar time during the day outside of wound 
care/dressing changes or applying the cream, for the first 7 days of treatment at 
home 

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• Rate overall skin pain each day, at a similar time during the day outside of wound 
care/dressing changes or applying the cream, for the first 7 days of treatment at 
home 
15.5. 
Data to be Considered as Source Data 
The following are considered source data: Informed consents, laboratory reports, patient 
files, IMP accountability list, and patient´s diary. 
The following information must be entered in the patient’s file: 
• Patient’s name, address and date of birth 
• Patient’s weight, height/length, and temperature 
• Medical history 
• Bandage history including (type of bandage used and frequency of usage) 
• Concomitant medication 
• Unambiguous reference to the clinical study (clinical study number, screening 
number and patient number) 
• Information on main selection criteria (diagnosis) 
• Dates of study drug administration and amount of drug used/returned by the 
subject  
• Date of informed consent / assent 
• Physical examinations and results done at the appropriate visits  
• Dates and time of urine pregnancy test 
• Body Surface Area calculation sheets for lesional skin and wound burden 
• Pain Scales 
• Itching Scales 
• Anatomical location of the target wound and corresponding ARANZ report with 
photograph 
• Documentation of EB diagnosis 
• Did AE(s) occur, improve or worsen? 
• Date of discontinuation / completion of the clinical study.   
• For patients that are lost to follow-up, the site is to document attempts made to 
contact the patient, ie, telephone, email, certified letter 
Relevant general medical and medication history needs to be checked and documented in 
the eCRF. 
All other data recorded directly in the eCRF (ie, no prior written or electronic record of 
data) will be considered as source data. 
15.6. 
Confidentiality 
The Investigator must assure that the patients’ anonymity will be maintained. On all 
study documentation, with the exception of the consent form, patient ID logs or as 

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otherwise outlined and agreed within the Informed Consent/Assent, patients will only be 
identified by their unique identification code and initials and will not be referred to by 
name. 
15.7. 
Retention of Study Data 
The Principal Investigator must maintain all documentation relating to the study for a 
period of 2 years after the last marketing application approval, or if not approved, 2 years 
following the discontinuance of the test article for investigation. If it becomes necessary 
for the Sponsor or the Regulatory Authority to review any documentation relating to the 
study, the Investigator must permit access to such records. During the study, the 
Investigator must make study data accessible to the Sponsor, IRB and the Food and Drug 
Administration. A file for each patient must be maintained that includes the signed ICF 
and copies of all source documentation related to that patient. The Investigator must 
ensure the availability of source documents from which the information on the eCRF was 
derived. 
15.8. 
Communication and Publication of Results 
The results of the study will be presented in an integrated Clinical Study Report 
according to GCP. 
The results from the study will be presented to the Principal Investigators when the 
statistical analyses have been completed. On the basis of these data, the CRO in 
cooperation with the Sponsor, will write and report on the trial. 
A summary of the Clinical Study Report will be sent to the regulatory authorities and to 
the IRB after termination of the study. 
The Clinical Study Report shall form the basis for a manuscript intended for publication 
in an international, scientific journal at a suitable time agreed to by the Sponsor. 
No data from the study will be published, presented, or communicated without the mutual 
agreement of the Sponsor. 
This is a multi-site study, and results from an individual site will not be published before 
the first multi-site publication by the Sponsor. If there is no multi-site publication within 
18 months after the study has been completed or terminated at all sites and all data have 
been received, an individual site will have the right to publish its results, subject to the 
following requirements: 
• Prior to submitting or presenting a manuscript or other study-related material to a 
publisher, reviewer, or other external party, the Investigator or site will provide 
the Sponsor with a copy of the manuscript or other material, and the Sponsor will 
have 60 days from receipt of the material to review it and comment.  

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• At the Sponsor’s request, the Investigator or site will remove any confidential 
information, other than study results, prior to submitting or presenting the 
material. 
• The Investigator or site will, at the Sponsor’s request, further delay publication or 
presentation for up to 120 days, to allow the Sponsor to protect its interests in any 
of its inventions described in the material (Netherlands CEC). 

PPD
PPD
PPD

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Principal Investigator Approval 
I agree to conduct the study according to the terms and conditions of this protocol, 
current Good Clinical Practice and with applicable regulatory requirements. All 
information pertaining to the study shall be treated in a confidential manner. 
 
 
 
 
Signature: 
_________________________ 
 
Date: __________________ 
 
 
Name of Principal Investigator 
 
 
 
 
 
 
Printed:           _________________________ 
 
 
Name of Principal Investigator 

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17. 
APPENDICES 
17.1. 
Appendix 1:  EB Subtypes 
Clinical Features of EB 
Epidermolysis Bullosa Simplex (EBS) 
EBS Subtypes  
Features  
Weber-Cockayne  
• Most common and localized form of EBS.  
• Blisters develop on hands and feet in response to friction.  
• Usually presents in infancy as child is starting to crawl and 
walk.  
• Lesions heal without scarring but there may be thickening of 
the skin on soles and palms.  
Koebner  
• Generalized EBS where blisters develop all over the body but 
commonly on hands, feet and extremities.  
• Presents at birth or early in infancy.  
• May be mild involvement of mucous membranes and nails.  
• Thickening of skin and plaques develop on palms and soles.  
Dowling-Meara  
• Generalized and severe form of EBS.  
• Presents at birth with blistering on the face, trunk and limbs.  
• Thickened skin may cause calluses that limit or interfere with 
joint movement.  
• Nails often affected.  
• May involve other organs including inside the mouth, 
gastrointestinal and respiratory tract.  
• Widespread involvement may cause death in infancy but 
usually there is significant improvement with age.  
EB with muscular 
dystrophy  
• Due to plectin mutation.  
• Variable degree of blistering followed later in life by muscular 
dystrophy.  
• Muscular dystrophy does not arise in all cases with plectin 
mutation.  
 

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Recessive Dystrophic Epidermolysis Bullosa (RDEB) 
DEB Subtypes  
Features  
Recessive DEB  
• May present with severe blistering (Hallopeau-Siemens) or 
mild disease (non-Hallopeau-Siemens).  
• Generalized severe blistering is more common and involves 
large areas of skin and mucous membranes.  
• Blisters heal but with scarring and deformity causing limited 
movement as fingers and toes may be fused together (mitten 
hands).  
• Complications such as infection, malnutrition and dehydration 
may cause death in infancy and those that survive are at great 
risk of developing squamous cell carcinoma.  
• Milia (small white cysts) are often present at healed but 
scarred sites. 
 
Junctional Epidermolysis Bullosa (JEB) 
JEB Subtypes  
Features  
Non-Herlitz JEB  
• Generalized blistering and mucosal involvement present at 
birth or soon after.  
• Scalp, nails and teeth involved.   
• Often sparse hair. 
• Complications such as infection, malnutrition and dehydration 
may cause death in infancy but many survive.  
 
 
 

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17.2. 
Appendix 2:  Itch Man Pruritus Assessment Tool 
 
 
 
Itch Man Pruritus Assessment Tool 
 
Reference: Morris V, Murphy L, Rosenberg M, Rosenberg L, Holzer C, Meyer W.  Itch 
Assessment Scale for the Pediatric Burn Survivor. Journal of Burn Care & Research. 2012; 33(3): 
419-424.  
 
 

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17.3. 
Appendix 3:  FLACC Behavioral Scale 
 
 
FLACC Behavioral Scale 
 
Categories 
Scoring 
0 
1 
2 
Face 
No particular expression or 
smile 
Occasional grimace or 
frown, withdrawn, 
disinterested 
Frequent to constant frown, 
clenched jaw, quivering chin 
Legs 
Normal position or relaxed 
Uneasy, restless, tense 
Kicking, or legs drawn up 
Activity 
Lying quietly, normal 
position, moves easily 
Squirming, shifting back and 
forth, tense 
Arched, rigid, or jerking 
Cry 
No cry (awake or asleep) 
Moans or whimpers, 
occasional complaint 
Crying steadily, screams or 
sobs, frequent complaints 
Consolability 
Content, relaxed 
Reassured by occasional 
touching, hugging, 
or being talked to, 
distractable 
Difficult to console or 
comfort 
Each of the five categories (F) Face; (L) Legs; (A) Activity; (C) Cry; (C) Consolability is scored from 0-2, 
which results in a total score between zero and ten. 
 
 
© 2002, The Regents of the University of Michigan. All Rights Reserved. 
 
 

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FLACC Behavioral Pain Scale 
 
Patients who are awake:  Observe for at least 1-2 minutes. Observe legs 
and body uncovered.  Reposition patient or observe activity, assess body for 
tenseness and tone.  Initiate consoling interventions if needed 
Patients who are asleep:  Observe for at least 2 minutes or longer.  
Observe body and legs uncovered.  If possible reposition the patient.  Touch 
the body and assess for tenseness and tone. 
 
Face 
Score 0 point if patient has a relaxed face, eye contact and interest in 
surroundings 
Score 1 point if patient has a worried look to face, with eyebrows lowered, 
eyes partially closed, cheeks raised, mouth pursed  
Score 2 points if patient has deep furrows in the forehead, with closed eyes, 
open mouth and deep lines around nose/lips  
 
Legs 
Score 0 points if patient has usual tone and motion to limbs (legs and arms) 
Score 1 point if patient has increase tone, rigidity, tense, intermittent 
flexion/extension of limbs 
Score 2 points if patient has hyper tonicity, legs pulled tight, exaggerated 
flexion/extension of limbs, tremors 
 

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Activity 
Score 0 points if patient moves easily and freely, normal 
activity/restrictions 
Score 1 point if patient shifts positions, hesitant to move, guarding, tense 
torso, pressure on body part 
Score 2 points if patient is in fixed position, rocking, side-to-side head 
movement, rubbing body part 
 
Cry 
Score 0 points if patient has no cry/moan awake or asleep 
Score 1 point if patient has occasional moans, cries, whimpers, sighs 
Score 2 points if patient has frequent/continuous moans, cries, grunts 
 
Consolability 
Score 0 points if patient is calm and does not require consoling 
Score 1 point if patient responds to comfort by touch or talk in ½- 1 minute 
Score 2 points if patient require constant consoling or is unconsoled after an 
extended time 
 
Whenever feasible, behavioral measurement of pain should be used in 
conjunction with self-report.  When self-report is not possible, 
interpretation of pain behaviors and decision making regarding treatment of 
pain requires careful consideration of the context in which the pain 
behaviors were observed. 
 

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Each category is scored on the 0-2 scale which results in a total score of 
0-10 
 
Assessment of Behavioral Score: 
0 = Relaxed and comfortable 
1-3 = Mild discomfort 
4-6 = Moderate pain 
7-10 = Severe discomfort/pain 
 
© 2002, The Regents of the University of Michigan. All Rights Reserved. 
 
 

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17.4. 
Appendix 4:  Wong-Baker FACES Pain Rating Scale 
 
 
 
Subject # ________   Wong-Baker FACES® Pain Rating Scale   Date_____________ 
 
 
 
No  
 
Hurts   
Hurts   
Hurts   
Hurts   
Hurts 
Hurt  
 
Little Bit  
Little More  
Even More  
Whole Lot 
Worst 
 
 
 
 
 
 
 
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