Conditions: Epidermolysis Bullosa
Keywords: Amicus Therapeutics Scioderm, Inc. Simplex Recessive Dystrophic Junctional non-Herlitz Epidermolysis Bullosa SD-101 6% SD-101-6.0 Allantoin 6% Zorblisa
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 169
Healthy volunteers: no

Brief summary:
The aim was to assess the efficacy and safety of SD-101-6.0 cream versus Placebo (SD-101-0.0) cream in the treatment of skin lesions in participants with Epidermolysis Bullosa. Funding Source - United States Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD).

Detailed description:
This was a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of SD-101-6.0 cream versus placebo (SD-101-0.0) cream on skin lesions in participants with Simplex, Recessive Dystrophic, or Junctional non-Herlitz Epidermolysis Bullosa. Epidermolysis Bullosa is a rare group of inherited disorders that typically manifest at birth as blistering and lesion formation on the skin in response to little or no apparent trauma. In this study, SD-101-6.0 cream or placebo (SD-101-0.0) cream was to be applied topically, once a day to the entire body for a period of 90 days. Participants had 1 target wound selected at baseline by the investigator. The selected target wound was required to have been present for at least 21 days. Photographic confirmation of the target wound location was collected at baseline, and the picture saved from the first visit was used to confirm location of the target wound at subsequent visits. The participant returned to the study site for Visit 2 (approximately 14 days from baseline), Visit 3 (approximately 30 days from baseline), Visit 4 (approximately 60 days from baseline), and Visit 5 (approximately 90 days from baseline) to have the target wound assessed for the level of healing. In addition, itching, pain, body surface area, target wound closure, and scarring of healed target wound were assessed at each visit. The ARANZ SilhouetteStar™ was used to measure the target wound at all visits.

Arms:
arm 1: SD-101-6.0 cream applied topically, once a day to the entire body for a period of 90 days arm 2: SD-101-0.0 (placebo) cream applied topically, once a day to the entire body for a period of 90 days

Interventions: intervention 1: SD-101-6.0 cream intervention 2: Placebo (SD-101-0.0) cream
Intervention descriptions: intervention 1: applied topically once a day for 90 days intervention 2: applied topically once a day for 90 days

Protocol document:
Prot_000.pdf: 
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: 
CONFIDENTIAL 
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) 
 
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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: 
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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: 
CONFIDENTIAL 
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.  


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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. 


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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 
 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 48 of 50  
 
 
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. 
 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 49 of 50  
 
 
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. 
 
 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-005 
SD-101 Dermal Cream  
 
Scioderm, INC. 
 
 
 
10 March 2017 (Version 4) 
 
 Page 50 of 50  
 
 
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 
 
 
 
 
 
 
 
www.wongbakerFACES.org 
 
 
 
 
©1983 Wong-Baker FACES®Foundation. Used with permission. 
 
 
 

SAP_001.pdf: 
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 Statistical Analysis Plan:  22 March 2018 
 


 
 
PROTOCOL SD-005 
 
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 
Statistical Analysis Plan 
Final Version 6.0 
Date 12 May 2017 
Amendment 1 to Final Version 6.0: 22 March 2018 
CONFIDENTIAL 
Sponsor: 
Scioderm, Inc. 
An Amicus Therapeutics Company 
4601 Creekstone Drive 
Suite 160 
Durham, NC 27703 
 
 
Scioderm, Inc., An Amicus Therapeutics Company 
Clinical Study Report 
16.1 Study Information 
Study SD-005 
11 May 2018 
 
Page 2 of 86


Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 2 of 85 
Revision History 
Version 
Date 
Prepared 
By 
Revision 
Author 
Comments 
Draft 1.0 
17Nov2014 
Chiltern 
First external draft 
Draft 2.0 
15Dec2014 
Chiltern 
Second external draft based on the Final 
Protocol, Version 2.0 dated 12Nov2014 
Draft 3.0 
20Jan2015 
Chiltern 
Third external draft after SAP meeting on 
19Dec2014 
Final 1.0 
05Feb2015 
Chiltern 
Final 
Final 2.0 
12May2015 
Chiltern 
Update with sensitivity analysis recommended 
by Regulatory; add primary confirmatory 
analysis; adjust windowing table 
Final 3.0 
06Aug2015 
Chiltern 
Update sensitivity analysis to have primary 
endpoint stratified by region tested using 
CMH; change secondary endpoint for change 
from lesional skin at Month 2 compared to 
Baseline and move Month 3 to exploratory 
Draft 4.0 
23Mar2016 
Scioderm 
Section Changes to Analyses Planned in the 
Protocol: Changes were introduced to align 
with the changes to the protocol: elevated the 
secondary endpoint of time to complete target 
wound closure within 3 months to a one of two 
primary endpoints, introduction of 
group-sequential procedure with two interim 
analyses IA1 and IA2, the time duration for the 
existing primary endpoint (proportion of 
patients experiencing complete wound closure 
of their target wound within two months) was 
changed to “within 3 months”, the primary 
missing data handling approach changed to 
multiple imputations, the primary analysis 
method for proportions was changed from 
Fisher’s exact test to logistic regression, 
proportion of patients experiencing complete 
target wound closure at 2 months was demoted 
to the first secondary efficacy endpoint, 
proportion of patients experiencing complete 
target wound closure at 1 month efficacy 
endpoint was moved from an exploratory to a 
secondary efficacy endpoint. 
Final 4.0 
19Sep2016 
Scioderm 
Section Changes to Analyses Planned in the 
Protocol: general clarifications and edits 
Draft 5.0 
16Feb2017 
Scioderm 
Update from co-primary to two primary 
endpoints. Remove references related to 
interim analyses. Rename secondary endpoints 
as key secondary endpoints and exploratory 
endpoints as other secondary endpoints. 
Update adjustment for covariates. 
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PPD


Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 3 of 85 
Final 6.0 
12May2017 
Scioderm 
Update safety analysis to describe details. Add 
subgroup analyses. Clarify study success 
criteria. Clarify efficacy analyses where 
needed by updating statistical methodology 
Table 3. 
Amendment 1 
of Final 6.0 
01Mar2018 
Scioderm 
Addition of subgroup analysis, removal of 
some sensitivity analyses, and update to the 
safety section 8.7. The amendment also lists 
pre-unblinding clarifications recorded in the 
Note to File of 08Aug2017. 
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PPD


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PPD
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Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 5 of 85 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS...............................8 
2. 
INTRODUCTION ......................................................................................................10 
3. 
STUDY OBJECTIVE .................................................................................................10 
4. 
STUDY DESIGN .......................................................................................................10 
4.1. 
General Design ...........................................................................................................10 
4.2. 
Method of Assignment of Patients to Treatment Groups ...........................................11 
4.3. 
Blinding ......................................................................................................................11 
4.4. 
Determination of Sample Size ....................................................................................11 
5. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSES ...............................................................................................................12 
5.1. 
Changes in the Conduct of the Study .........................................................................12 
5.2. 
Changes from the Analyses Planned in the Statistical Analysis Plan ........................12 
6. 
BASELINE, EFFICACY AND SAFETY EVALUATIONS .....................................13 
6.1. 
Schedule of Evaluations .............................................................................................13 
6.2. 
Time Point Algorithms ...............................................................................................13 
6.2.1. 
Relative Day ...............................................................................................................13 
6.2.2. 
Analysis Windows ......................................................................................................13 
6.3. 
Efficacy Endpoints ......................................................................................................14 
6.3.1. 
Primary Efficacy Endpoints ........................................................................................14 
6.3.2. 
Key Secondary Efficacy Endpoints ............................................................................15 
6.3.3. 
Other Secondary Efficacy Endpoints ..........................................................................16 
6.4. 
Safety Endpoints .........................................................................................................16 
6.4.1. 
Extent of Exposure and Compliance to Study Drug ...................................................16 
6.4.2. 
Treatment-emergent Adverse Events .........................................................................17 
6.4.3. 
Vital Signs ..................................................................................................................17 
6.4.4. 
Physical Examination .................................................................................................17 
7. 
STATISTICAL METHODS .......................................................................................17 
7.1. 
General Methodology .................................................................................................17 
7.2. 
Adjustments for Covariates ........................................................................................18 
7.3. 
Handling of Dropouts or Missing Data ......................................................................18 
7.4. 
Multi-center Studies and Pooling of Centers ..............................................................19 
7.5. 
Multiple Comparisons/Multiplicity ............................................................................19 
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Statistical Analysis Plan 
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7.6. 
Examination of Subgroups .........................................................................................20 
8. 
STATISTICAL ANALYSIS ......................................................................................21 
8.1. 
Disposition of Patients ................................................................................................21 
8.2. 
Demographic and Other Baseline Characteristics ......................................................21 
8.3. 
Protocol Deviations ....................................................................................................21 
8.4. 
Analysis Populations ..................................................................................................22 
8.4.1. 
Intent-to-Treat (ITT) Population .................................................................................22 
8.4.2. 
Safety (SAF) Population .............................................................................................22 
8.4.3. 
Per Protocol (PP) Population ......................................................................................22 
8.5. 
Prior and Concomitant Therapy ..................................................................................22 
8.6. 
Analysis of Efficacy Endpoints ..................................................................................23 
8.6.1. 
Analysis of the Two Primary Efficacy Endpoints ......................................................23 
8.6.1.1. 
Statistical Methods ......................................................................................................23 
8.6.1.2. 
Sensitivity Analyses ....................................................................................................25 
8.6.2. 
Analysis of Key Secondary Efficacy Endpoints .........................................................25 
8.6.3. 
Analyses of Other Secondary Endpoints ....................................................................32 
8.7. 
Analysis of Safety .......................................................................................................33 
8.7.1. 
Extent of Exposure and Compliance of Study Drug ..................................................33 
8.7.1.1. 
Extent of Exposure .....................................................................................................33 
8.7.1.2. 
Measurements of Treatment Compliance ...................................................................33 
8.7.2. 
Adverse Events by Preferred Term and System Organ Class ....................................33 
8.7.3. 
Summaries of Adverse Event Incidence Rates for All Subjects.................................34 
8.7.4. 
Missing AE Onset, Severity, and Relationship ..........................................................34 
8.7.4.1. 
Missing or Partial AE Dates .......................................................................................34 
8.7.4.2. 
Missing Severity .........................................................................................................35 
8.7.4.3. 
Missing Relationship ..................................................................................................35 
8.7.5. 
Summaries of Adverse Event Incidence Rates for Serious Adverse Events 
(SAE), Adverse Event Dropouts, and Death ..............................................................35 
8.7.6. 
Discontinuation from the Study ..................................................................................36 
8.7.7. 
Clinical Laboratory Evaluations .................................................................................36 
8.7.7.1. 
Pregnancy Test ............................................................................................................36 
8.7.8. 
Other Observations Related to Safety .........................................................................36 
8.7.8.1. 
Vital Signs ..................................................................................................................36 
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Statistical Analysis Plan 
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Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 7 of 85 
8.7.8.2. 
Physical Examination Findings ..................................................................................36 
8.7.8.3. 
Skin Infections ............................................................................................................36 
9. 
COMPUTER SOFTWARE ........................................................................................37 
10. 
REFERENCES ...........................................................................................................37 
11. 
APPENDICES ............................................................................................................38 
11.1. 
Body Surface Area Index (BSAI) of Lesional Skin ...................................................38 
11.2. 
Body Surface Area Index (BSAI) of Total Wound Burden .......................................39 
11.3 
List of Tables ..............................................................................................................40 
11.4 
List of Figures .............................................................................................................76 
11.5 
List of Listings ............................................................................................................84 
 
LIST OF TABLES 
Table 1: 
Analysis Windows ......................................................................................................13 
Table 2: 
Concomitant Medications of Interest ..........................................................................23 
Table 3: 
Analysis Strategy for Efficacy Endpoints ..................................................................26 
 
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Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 8 of 85 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
BSAI 
Body Surface Area Index 
oC 
Degrees Celsius 
CI 
Confidence Interval 
cm 
centimeters 
CRF 
Case Report Form 
d/c 
discontinuation 
EB 
Epidermolysis Bullosa 
EBS 
Epidermolysis Bullosa Simplex 
FDA 
Food and Drug Administration 
FLACC 
Face, Legs, Activity, Cry, Consolability 
HR 
Hazard Ratio 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response Services 
JEB 
Junctional non-Herlitz EB 
K-M 
Kaplan-Meier 
MAR 
Missing at Random 
MCMC 
Markov Chain Monte Carlo 
MI 
Multiple Imputation 
MMRM 
Mixed Model Repeated Measures 
MNAR 
Missing Not at Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
NTF 
Note to File 
PP 
Per Protocol 
PT 
Preferred Term 
RDEB 
Recessive Dystrophic Epidermolysis Bullosa 
ROW 
Rest of the World 
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Statistical Analysis Plan 
CONFIDENTIAL 
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Protocol: SD-005 
22 March2018 
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SAE 
Serious Adverse Event 
SAF 
Safety analysis population 
SAP 
Statistical analysis Plan 
SOC 
System Organ Class 
TBWB 
Total Body Wound Burden 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
WHO 
World Health Organization 
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Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 10 of 85 
2. 
INTRODUCTION 
The SAP (Statistical Analysis Plan) was finalized prior to database lock (submitted to the Food 
and Drug Administration (FDA) on 16 May 2017 in Serial No. 0093) and is consistent with the 
Amendment 3, version 4.0 dated 10 March 2017 of the protocol. This amendment incorporates 
clarifications presented in the pre-database lock Note to File (NTF) of 8 August 2017, as well as 
post-database lock addition of further subgroup analyses and removal of some sensitivity 
analyses. 
3. 
STUDY OBJECTIVE 
The primary objective is to evaluate the efficacy and safety of SD-101-6% vs. Placebo in patients 
with Epidermolysis Bullosa Simplex (EBS), Recessive Dystrophic Epidermolysis Bullosa 
(RDEB), or Junctional non-Herlitz Epidermolysis Bullosa (JEB). SD-101-6% is the treatment 
referred to in the study protocol as SD-101-6.0. Placebo is the treatment referred to in the study 
protocol as SD-101-0.0. 
4. 
STUDY DESIGN 
4.1. 
General Design 
This is a Phase 3, multi-center, randomized, double-blind, placebo controlled study to assess the 
efficacy and safety of SD-101-6% cream vs. Placebo on 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% cream or Placebo cream. 
SD-101-6% or Placebo will be applied topically, once a day to the entire body for a period of 
90 days.  
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 (captured as wound 
A in the ARANZ system) is identified for the study. 
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 drug. 
The patient will return for scheduled visits in accordance with the protocol: 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 
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Statistical Analysis Plan 
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Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 11 of 85 
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 and tolerability assessments will include monitoring of AEs (Adverse Events) and 
physical examinations. 
Patients who complete the study will be eligible to enroll into an open-label study (SD-006). 
4.2. 
Method of Assignment of Patients to Treatment Groups 
Approximately 150 patients will be randomized using Interactive Web Response System (IWRS) 
to 1 of 2 treatment groups: Placebo or SD-101-6%. Patients are randomized using a 1:1 scheme. 
4.3. 
Blinding 
The blinding code will be produced by an independent unblinded team designated by Scioderm, 
who will provide safety oversight for the study. A patient will be unblinded only if the 
Investigator feels that knowledge of the specific treatment is necessary to determine how to treat 
the patient. In an emergency situation, the Investigator may need to break the code immediately, 
or as quickly as possible, if he/she finds it is in the best interest of the patient. The Investigator 
will be able to unblind using the IWRS system. If the blinding is prematurely broken, it is the 
responsibility of the Investigator to promptly document and explain any unblinding to the 
Sponsor. Any unblinding will be monitored for prompt documentation. 
4.4. 
Determination of Sample Size 
The two 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 
Complete target wound closure is defined as skin re-epithelialization without drainage.  
These endpoints will be compared between SD-101-6% and Placebo, and tested via a step-down 
procedure beginning with the time to complete target wound closure. This will address 
multiplicity and control the overall study type 1 error level at 0.025 1-sided (refer to Section 7.5 
for more detail).  
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% 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 remain as 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 
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Statistical Analysis Plan 
CONFIDENTIAL 
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Protocol: SD-005 
22 March2018 
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Page 12 of 85 
treatment, which corresponds to a hazard ratio HR=2.127. These yield the 35% expected wound 
closures for placebo (35% = 100% - 65% surviving open), and 60% for SD-101-6% 
(60% = 100% - 40% surviving open). Approximately 150 patients are required (75 in each 
group) to provide at least 86% power for the 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.  
5. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES 
5.1. 
Changes in the Conduct of the Study 
There were no changes in the conduct of the study at the time of preparing this statistical analysis 
plan. 
5.2. 
Changes from the Analyses Planned in the Statistical Analysis Plan 
The following changes were made to the analyses planned in the Version 6.0 of the SAP dated 
12 May 2017: 
• Wound age subgroup analysis is only conducted for ≤30 days and >30 days 
subgroups. 
• Subgroups of interest were defined post-database lock. These are; 
− Age of 2 years to <12 years old 
− Wound age >30 days 
− Total Body Wound Burden (TBWB) ≥ 5% at Baseline 
− Age of 2 years to <12 years old plus TBWB ≥ 5% at Baseline 
− Age of 2 years to <12 years old at Baseline plus RDEB. 
• Subgroup analyses for gender, race, and region were not performed except for AEs 
and Serious Adverse Events (SAEs) leading to d/c (discontinuation). 
• In general, subgroup analyses were performed only for the 6 "subgroups of interest" 
(ie, 2 to <12 years, target wound age >30 days, TBWB ≥ 5%, and the 2 combined 
groups as specified above with exception of demographics and some efficacy 
analyses. Details are provided in the appendices. 
• Addition of time to event analysis truncated at Day 44. 
• Addition of wound size reduction to efficacy analysis. 
• Removal of some sensitivity analyses. 
• Removal of subgroup analyses for itching and pain based on who was an evaluator. 
• Addition of skin infection analysis. 
The detailed list of tables and figures is provided in the appendices. 
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Statistical Analysis Plan 
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6. 
BASELINE, EFFICACY AND SAFETY EVALUATIONS 
6.1. 
Schedule of Evaluations 
The assessments to be conducted at each scheduled visit are displayed in the protocol. 
6.2. 
Time Point Algorithms 
6.2.1. 
Relative Day 
The date of randomization or Visit 1, will be considered study Day 0. Days prior to Day 0 will be 
negative. Day of randomization will be used to establish visit windows. Study days will be 
calculated as f:  
date of assessment – date of randomization. 
For relative day on study drug, the date of first study drug administration will be used. The first 
date of drug administration will be either the randomization day or the first day of study drug 
administration recorded on diary, if the study drug was not administered during the 
randomization office visit. 
The relative day on study drug will be calculated as: 
date of assessment – date of the first study drug administration + 1. 
6.2.2. 
Analysis Windows 
For analysis purposes, the visit numbers will be allotted into windowed visits, as illustrated in the 
following table. 
Table 1: 
Analysis Windows 
Week 
Visit 
Scheduled Study Day 
Visit Window for Analysis 
(Days) 
Screening/Baseline 
Visit 1 
-7 to 0 
Day -7 – Day 0 
Randomization 
Visit 2 
0 
Day 0 
Week 2 
Visit 3 
14 
Day 1 – Day 21 
Month 1 
Visit 4 
30 
Day 22 – Day 45 
Month 2 
Visit 5 
60 
Day 46 – Day 75 
Month 3 / Final Visit 
Visit 6 
90 
Day 76 – Completion 
As per the NTF, for the first primary endpoint (time to wound closure), the time to the first 
wound closure will be utilized irrespective of visit windows. For the second primary endpoint 
(proportion of subjects experiencing complete closure of their target wound), if there are more 
than one visit within the assigned visit window and the complete target wound closure occurred 
at any of them, it would count as wound closure at that visit. In case of the Month 3 / Final Visit 
analysis, even if the visit falls prior to Day 76 it will be utilized (example: there are two visits in 
the Month 2 visit window - Day 46 and Day 75. Day 75 visit is the last one. Day 46 visit will be 
utilized as Month 2 visit and Day 75 will be utilized as Month 3/ Final Visit. For the secondary 
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Statistical Analysis Plan 
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endpoints, the following approach will be used. The visit closest to the scheduled study day will 
be used for analysis. If two visits are the same distance from the scheduled study day, the first 
one will be used. In case of the Month 3 /Final Visit analysis, even if the visit falls prior to Day 
76 it will be utilized (example: there are two visits in the Month 2 visit window- Day 46 and Day 
75. Day 75 visit is the last one. Day 46 visit will be utilized as Month 2 visit and Day 75 will be 
utilized as Month 3 / Final Visit. If an unscheduled visit comprises only of dispensing or 
returning of study drug, it will not count for determination of the study visit used for the analysis. 
This way all data available will be utilized. 
6.3. 
Efficacy Endpoints 
6.3.1. 
Primary Efficacy Endpoints 
The two primary efficacy endpoints for this study are:  
• Time to complete target wound closure within 3 months.  
• Proportion of patients experiencing complete closure of their target wound within 
3 months. Time to complete wound closure is based on the date of the first 
administration of the study drug. 
As the clarification in the NTF, if the target wound closes at a given visit, it will be 
considered closed at all subsequent visits. 
They will be tested in a step-down procedure with the time to complete target wound closure 
being the first tested. If the time to complete target wound closure endpoint is statistically 
significant at the alpha level 0.025 one-sided, the endpoint ‘proportion of patients experiencing 
complete target wound closure within 3 months’ will be formally tested. The study will be 
considered a success if the first primary endpoint achieves statistical significance (refer to 
Section 7.5 for more detail). 
As per clarifications in the NTF, the first primary efficacy analysis will be done on the ITT 
(Intent-To-Treat) population defined as all patients who were randomized. For clarification, the 
time to first wound closure analysis being conducted in the ITT population will inherently 
include patients with at least one post-Baseline assessment of target wound. 
For the second primary endpoint of wound closure within 3 months, missing values imputed 
using the values observed at previous visits in multiple imputations, will be used in a logistic 
regression model to compare treatment groups while adjusting for baseline factors. In addition, 
for the second primary endpoint of wound closure within 3 months, a sensitivity analysis will be 
performed to assess the robustness of the imputation method: patients who do not experience 
wound closure will be considered as treatment failures; all patients who are randomized are 
analyzed (ITT). 
As defined post database lock, primary efficacy analyses will be performed only on one 
subgroup based on the actual target wound age at baseline: ≤30 days, and >30 days. 
In addition, the analyses will be also performed for subgroups of interest. 
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6.3.2. 
Key Secondary Efficacy Endpoints 
The 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. 
Lesional skin for assessment consists of area(s) that could contain any of the 
following: blisters, erosions, ulcerations, scabbing, bullae, and eschars, as well as 
areas that are weeping, sloughing, oozing, crusted, and denuded. BSAI is the percent 
of this area recorded for each defined body region (number from 0-100% assigned for 
each region). Other areas categorized as skin that is either healed or scarred are not 
considered lesional skin. The BSAI will be assessed by a study physician for each 
patient visit. Complete calculations are listed in Appendix  11.1. 
• Change in TBWB at Month 3, compared to Baseline. 
A wound is defined as an open area on the skin (epidermal covering is disrupted). 
Complete calculations are listed in Appendix 11.2. 
• Change in itching assessed at Day 7, compared to Baseline, where change is defined 
as Day 7 itching value minus the Baseline value. 
If the assessment on Day 7 is missing, then an assessment window of ±2 days will be 
utilized. The assessments closest toDay 7 will be used and if two assessment are same 
distance from Day 7, then the latest would be used (examples: Day 6 present, Day 7 
missing, Day 8 missing, Day 9 present - Day 6 will be used; Day 6 present, Day 7 
missing, Day 8 present – Day 8 will be used). 
Change in itching assessed at 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. The “Itch Man Pruritus Tool” rates 
itching on a scale from 0 to 4, where larger values indicate more itching. 
• Change in pain assessed at Day 7, compared to Baseline, where change is defined as 
Day 7 pain value minus the Baseline value. 
If the assessment on Day 7 is missing, then an assessment window of ± 2 days will be 
utilized. The assessments closest to Day 7 will be used and if two assessment are 
same distance from Day 7 then the latest would be used (examples: Day 6 present, 
Day 7 missing, Day 8 missing, Day 9 present - Day 6 will be used; Day 6 present, 
Day 7 missing, Day 8 present – Day 8 will be used). 
Change in pain assessed at Day 7, compared to Baseline will be measured using the 
“FLACC Behavioral Scale” for patients 1 month to 3 years of age, and for patients 
4 years of age and older the “Wong-Baker FACES Pain Rating Scale” will be 
utilized. The FLACC Behavioral Scale (Face, Legs, Activity, Cry, Consolability) is a 
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measurement to assess pain in children or persons unable to communicate pain. Each 
of the five categories are scored from 0 to 2, resulting in a total score from 0 to 10. 
The “Wong-Baker FACES Pain Rating Scale” is a scale that shows a series of faces 
ranging from a happy face at 0 to a crying face at 10. For both scales, larger scores 
equate to more pain. 
The analysis will be performed on the ITT population and subgroups of interest. 
6.3.3. 
Other Secondary Efficacy Endpoints 
The additional efficacy endpoints are: 
• Change in Total Body Wound Burden based on BSAI at Week 2, Months 1, and 2, 
compared to Baseline. 
• Percent change from Baseline in Total Body Wound Burden based on BSAI at 
2 Week 2 weeks, Months 1, 2, and 3. 
• Change in lesional skin based on BSAI at Week 2,Months 1, and 2, compared to 
Baseline. 
• Percent change in lesional skin based on BSAI at Week 2, 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, Months 1, 2, and 3, compared to Baseline.  
• Changes 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. 
The analysis will be performed on the ITT population and subgroups of interest. 
6.4. 
Safety Endpoints 
6.4.1. 
Extent of Exposure and Compliance to Study Drug 
SD-101-6% or Placebo creams will be supplied in 8 ounce plastic tubes, to be reclosed after use 
and stored at room temperature. SD-101-6% or Placebo will be applied topically once a day to 
the entire body for a period of 90 days. The first dose of study drug will be administered during 
the first study visit after randomization and enrollment visit assessments as described in 
Section 6.1. 
The patient diary will be returned at visits 3, 4, and 5 to evaluate compliance. 
Compliance with study drug is based on drug usage recorded in the patient diary. It will be 
calculated as follows: 
Compliance (%) = 100*(number of days cream applied / days on study) 
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6.4.2. 
Treatment-emergent Adverse Events 
Treatment-emergent AEs (TEAEs) are undesirable experiences, signs, or symptoms that begin or 
change in severity or relationship to treatment at the time of or after the first administration of 
study drug prior to the end of study. 
The investigator’s verbatim term of both serious and non-serious AEs will be mapped to system 
organ class (SOC) and preferred terms (PTs) using the 19.1 version of the Medical Dictionary for 
Regulatory Activities (MedDRA). Partial dates will be imputed as the following: 
1. If year is not missing and is after the year of first application of study drug: 
a. If Month is missing, then Month will be imputed as January 
b. If Day is missing, then Day will be imputed as the first of the month 
2. If year is not missing and is the same as the year of the first application of study drug: 
a. If Month is missing, then impute the Month as the month of the first application of 
study drug 
b. If Day is missing but Month is on or after the month of first application of study drug, 
then impute Day as the first day of study drug application 
3. If year is missing, then impute the year as the year of the first study drug application: 
a. If Month is missing, then impute the Month as the Month of the first drug application 
b. If Day is missing, then impute the Day as the day of the first study drug application. 
4. If the start date is completely missing, but the AE is either ongoing or the stop date is 
after the first date of drug application, then impute the start date as the first date of drug 
application. 
5. If using the above rules, the stop date is before the start date, then leave the stop date 
missing and assume that AE is treatment emergent for the purpose of the analysis. 
6.4.3. 
Vital Signs 
Vital signs (temperature, height/length, and weight) are a part of the physical examination, which 
will be performed at the Screening visit and Month 3/ Final visit. All vital signs will be reported 
in metric units. 
6.4.4. 
Physical Examination 
Physical examinations will be done by a physician at the Screening visit and Month 3 /Final 
visit. 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. 
7. 
STATISTICAL METHODS 
7.1. 
General Methodology 
For statistical analysis purposes, Baseline is defined as the last measurement prior to the first 
application of the study drug. 
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In general, no formal inferential analyses are planned for the Baseline and safety data, and only 
descriptive statistics will be provided. 
For the descriptive statistics, the categorical variables will be summarized by frequency and 
percentage for each response category (number of patients, %) and the continuous variables will 
be summarized using means, medians, minimum, maximum, and standard deviations.  
Data will be summarized by treatment groups, and overall (where appropriate). 
7.2. 
Adjustments for Covariates 
Epidermolysis Bullosa (EB) type and Baseline characteristics of the target wound at Baseline, 
(ie., target wound size and target wound age) are considered to be potential effect modifiers. 
Their effects will be considered for the two primary efficacy endpoints (Month 3) as covariates.  
Wound age is based on the wound start date provided by the subject from recall and as clarified 
in the NTF, it is calculated as follows: calculated wound age = Baseline date-wound start date. If 
the calculated wound age is ≤365 days then wound age used as a covariate in analysis is the 
calculated wound age. If the calculated wound age is >365 days, then the wound age used as 
covariate in analysis is replaced by 365 days. The reason for the definition is that it is difficult 
for the subject to provide an exact wound start date for old wounds. 
Same covariates will be used in analysis of wound closure endpoints at other time points. 
For other endpoints, EB type and the Baseline value for a given endpoint will be used. 
7.3. 
Handling of Dropouts or Missing Data 
For the time to wound closure endpoint, data will be right censored at 3 months or at the time of 
patient’s withdrawal from the study. For the second primary endpoint and for the binary 
secondary endpoints of wound closure, the first method of imputation for missing data will be 
Multiple Imputation (MI) using the Missing At Random (MAR) assumption. As clarified in the 
NTF, if the target wound closure occurred at a prior visit, the target wound is considered closed 
at all subsequent visits that took place. In such a case, no imputation is required for subsequent 
visits.  
For the first MAR based multiple imputation, the MI procedure of the SAS® system will be used 
to generate sets of data with missing values imputed from observed data. It is expected that the 
pattern of missing data will be monotonic, with slight deviations being corrected by the 
Markov Chain Monte Carlo (MCMC) method of the MI procedure. 
As per clarification in the NTF, after the MCMC correction, the rounding will be performed for 
the binary endpoint. If imputed values are greater than or equal to 0.5, the value is set to 1 and 
anything else is set to 0. 
Linear regression will be employed to model the missing continuous data and a logistic 
regression model will be used for the binary data, with the following covariates included in the 
imputation model: treatment, EB type, Baseline characteristics of a given endpoint (as described 
in Section 7.2), and non-missing data from earlier time points. As per clarification in the NTF, if 
the Week 2 data for wound closure are missing. there are no previous visit data available to 
utilize in the imputation procedure. Therefor,e patients with missing Week 2 wound closure data 
will be excluded from analysis. The imputed datasets will be analyzed using the methodology 
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described in Section 8. The results from the analysis of the multiple imputed datasets will be 
combined by the MIANALYZE procedure of the SAS system. The seed number to be used will 
be 010005 and the number of imputations is planned to be 5. 
The final p-value, estimate of regression coefficient for treatment effect, and the 95% CI of the 
estimate of the treatment effect on each multiply-imputed dataset will be generated from the 
MIANALYZE procedure of SAS. 
In addition, for the proportion of complete wound healing within Month 3, the final difference in 
proportions between treatment groups (SD-101-6% - Placebo) and the 95% CI of the final 
difference from each multiply imputed dataset will be generated using the method by Bohdana 
Ratitch et al. 2013. 
To assess the robustness of the first missing data imputation result for the second primary 
endpoint, the following sensitivity analyses will also be conducted: 
a. The same multiple imputation method as above will be repeated but based on the 
Pattern-Mixture Model discussed by Bohdana Ratitch et al. 2013 under the Missing 
Not At Random (MNAR) assumption, by using the profiles from the placebo subjects 
with observed data to imput missing data 
b. Subjects with missing wound healing data within 3 months will be considered as 
‘failures’ for the wound healing rate 
7.4. 
Multi-center Studies and Pooling of Centers 
All study sites will be included in the statistical analyses. However sites will be pooled according 
to geographic regions (US, Europe, and Rest of the World [ROW]). 
7.5. 
Multiple Comparisons/Multiplicity 
The two 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% and Placebo, 
and tested via a step-down procedure beginning with the time to complete target wound closure. 
This will address multiplicity and control overall type 1 error level at 0.0-5 2-sided. Note that if 
the first primary endpoint to be tested (time to complete wound closure within 3 months) meets 
the significance criterion of p<0.05 2-sided the study will be declared a success. If the first 
primary endpoint does not meet the significance criterion, the second primary endpoint 
(proportion of patients experiencing complete closure of the target wound within 3 months) will 
not be formally tested.Formal testing of the first key secondary endpoint at 0.05 2-sided will 
proceed (which is equivalent to 0.025 1-sided) if both primary endpoints are significant. If the 
first key secondary endpoint is statistically significant, then the second endpoint on the list of the 
key secondary endpoints will be tested at the two-sided 0.05 alpha level. Formal statistical 
testing will not proceed to the next endpoint if the current endpoint does not reach statistically 
significant level of 0.05 (two-sided). While the formal statistical testing will not proceed, 
nominal p-values will be generated for all endpoints.  
Following the evaluation of the two primary endpoints, the ranking of the key secondary 
endpoints is as follows:  
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1. Proportion of patients experiencing complete closure of their target wound within 
2 months 
2. Proportion of patients experiencing complete closure of their target wound within 
1 month 
3. Change in lesional skin based on BSAI at Month 3, compared to Baseline 
4. Change in Total Body Wound Burden at Month 3, compared to Baseline 
5. Change in itching assessed at Day 7, compared to Baseline 
6. Change in pain assessed at Day 7, compared to Baseline 
The inclusion of other secondary endpoints listed in Section 6.3.3 is intended to yield supportive 
evidence related to the primary and key secondary objectives. Statistical tests of these variables 
are considered exploratory and no adjustment for multiplicity for these other secondary 
endpoints will be made. 
7.6. 
Examination of Subgroups 
All subgroup analyses are exploratory in nature and serve the purpose of numerical assessment 
of consistency of treatment effects across subgroups. 
Subgroups if interest have been defined post-database lock. These are 
• Age of 2 years to <12 years old 
• Wound age >30 days 
• Total Body Wound Burden (TBWB) ≥5 % at Baseline 
• Age of 2 years to <12 years old plus TBWB ≥ 5% at Baseline 
• Age of 2 years to <12 years old at baseline plus RDEB. 
In general, subgroup analyses are performed only for the 6 "subgroups of interest" (ie, 2 to 
< 12, target wound age >30 days, TBWB ≥ 5%, and the 2 combined groups as specified above 
with exception of demographics and some efficacy analyses. Details are provided in the 
appendices. 
Subgroups for subject’s age are defined based on the subject’s age at Baseline. For the purpose 
of subgroup analysis, race will be classified as White and Non-White.  
For subgroup analysis of of the two primary and key secondary endpoints, -treatment effects, 
nominal p-values and nominal 95% CI by category of the classification variables listed above 
will be presented.  
Based on the medical review of ARANZ SilhouetteStar system data prior to unblinding, the 
location of target wound will be determined to be in the flexure (eg. elbow, knee) or non-flexure 
region. Proportion of patients experiencing complete closure of their target wound within each 
visit, as well as itching and pain assessment at Day 7 are to be performed for these subgroups. 
Subgroup analyses for gender, race, and region were performed for AEs and SAEs leading to d/c. 
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8. 
STATISTICAL ANALYSIS 
8.1. 
Disposition of Patients 
The number and percentage of patients who were screened, randomized, treated, completed, 
discontinued, and the primary reason for discontinuation based on the CRF (Case Report Form) 
termination page will be displayed. In addition, the number and percentage of subjects in each 
study population (ie., Intent-to-Treat population [ITT], Safety population [SAF] and Per Protocol 
population [PP]) as defined in Section 8.4 will be summarized by treatment group. 
Same summaries will be produced for each investigational site, by country, and by region. 
8.2. 
Demographic and Other Baseline Characteristics 
Descriptive summaries of demographic and Baseline characteristics will be presented for the ITT 
and SAF populations. If the ITT and the SAF populations are identical, then the summaries will 
be based on ITT population only. 
Continuous variables such as patient age, weight, height/length, body mass index (BMI), body 
surface area (BSA) calculated by Mosseler formula, body surface area index BSAI (for lesion 
and wound burden), age of target wound, target wound size, and temperature will be summarized 
as described previously.  
Categorical variables such as patient gender, race, and age (0 to 27 days, 28 days to < 2 years, 
2 years to < 12 years, 12 years to < 18 years, ≥ 18 years), age of target wound (≤ Median, 
> Median; and 0 ≤ 30 days, 31≤ 60 days, 61 ≤ 90 days, > 90 days), will be summarized using 
number of observations and percentages for each category. 
Demographics is also presented for subgroups of interest. 
Medical history, including disease history and EB type, will be summarized and listed. 
Age will be defined as follows: 
• If age was collected instead of the birth date then, the collected value will be used, 
• If the birth date was collected, then  
Age = (date of informed consent date - date of birth + 1) / 365.25 and truncated to 
completed years. 
Weight will be displayed in kg, height/length will be displayed in centimeters (cm), and 
temperature will be displayed in degrees Celsius (oC). 
8.3. 
Protocol Deviations 
Number and percentage of subjects with major protocol deviations will be summarized for each 
treatment group in the ITT population and for subgroups as outlined in detail in the appendices. 
A listing of subjects with major protocol deviations will also be provided; major protocol 
deviations are further described in Section 8.4.3. 
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8.4. 
Analysis Populations 
ITT population will be used for all efficacy analyses. SAF population will be used for all safety 
analyses. PP population will be used for supportive analyses of the efficacy endpoints. 
If the SAF and ITT populations are identical, then the efficacy and safety analyses will be 
performed using the ITT population only. 
8.4.1. 
Intent-to-Treat (ITT) Population 
ITT population will be defined as all patients who have been randomized. These patients will be 
analyzed according to the assigned treatment. 
8.4.2. 
Safety (SAF) Population 
SAF population is defined as all randomized patients who applied/were administered the study 
drug at least once. These patients will be analyzed according to the treatment actually received. 
8.4.3. 
Per Protocol (PP) Population  
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 
2. Non-compliance to study drug (as defined by compliance to study drug <70% as 
perpatient diary)  
3. Administrative dispensing errors  
A final list of patients who have any major protocol deviations will be documented before final 
database lock. A listing will also be created. 
8.5. 
Prior and Concomitant Therapy  
The World Health Organization (WHO) Drug Dictionary Version of March 2017 will be used to 
classify medications. Any medication taken before and continuing after randomization, or 
initiated after randomization, is considered a concomitant medication. Any medication given 
before randomization but discontinued prior to randomization is considered a prior medication. 
A medication can be considered both prior and concomitant. Medications missing both start and 
stop dates, or having a start date prior to the last dose of study drug and missing the stop date, or 
having a stop date after the start of study drug and missing the start date, will be considered 
concomitant. Medications will also be considered concomitant if partial start and stop dates are 
present but it cannot be determined if the medication ended prior to start of study drug. 
A summary table will be provided for each of the following in the safety population: 
1. Number and percentage of subjects who had previous therapies/medications by 
Anatomical Therapeutic Chemical (ATC) code text and WHO drug name 
2. Number and percentage of subjects who had concomitant therapies/medications by ATC 
text and WHO drug name 
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The summary of use will also be provided for the groups of drug classes of concomitant 
medications listed in the table below: 
Table 2: 
Concomitant Medications of Interest 
SD-101-6% 
Placebo 
Timepoint 
or duration 
Drug Class 
All subjects 
Subgroups of 
interest 
All subjects 
Subgroups 
of interest 
Entire study 
A06A: drugs for constipation A11: vitamins 
A12: mineral supplements 
All subjects 
Subgroups of 
interest 
All subjects 
Subgroups 
of interest 
Entire study 
B03: antianemic drugs 
B05: blood substitutes and perfusion solutions 
J01: antibacterial drugs 
J02: antimycotic drugs 
All subjects 
Subgroups of 
interest 
All subjects  
Subgroups 
of interest 
Entire study 
N02: analgesic drugs 
N05: psycholeptic drugs 
N06: psychoanaleptics 
All subjects 
Subgroups of 
interest 
All subjects 
Subgroups 
of interest 
Entire study 
R06: antihistamines for systemic use 
All subjects 
Subgroups of 
interest 
All subjects 
Subgroups 
of interest 
Entire study 
V20: surgical dressings 
D09: medicated dressings 
D08: antiseptics and disinfectant drugs 
D06: antibiotics for derm use 
D03: treatment of wounds and ulcers 
All subjects 
Subgroups of 
interest 
All subjects 
Subgroups 
of interest 
At Baseline 
D07: topical dermatological corticosteroids 
H02: corticosteroid systemic 
L04A: immunosuppressant drugs 
8.6. 
Analysis of Efficacy Endpoints 
Table 3 in Section 8.6.2 summarizes the efficacy endpoints analyses. 
8.6.1. 
Analysis of the Two Primary Efficacy Endpoints 
8.6.1.1. 
Statistical Methods 
The two 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% and Placebo, 
and tested via a step-down procedure beginning with the time to complete target wound closure. 
Each endpoint might have analysis performed by primary and supportive methods. 
The statistical methodology is as follows: 
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• Time to complete target wound closure 
As clarified in the NTF, time to event analyses will be summarized using a Kaplan-
Meier approach, where the event is complete target wound closure measured from the 
date of the first administration of the study drug to the date of wound closure. Patients 
will be censored if they did not have a response within 3 months, or withdraw early, 
before the confirmation of their target wound closing. Comparison of the treatment 
groups will be performed using the Cox-proportional model with Baseline target 
wound size, target wound age, and EB type as covariates. The p-value, hazard ratio 
(HR), and 95% CI (Confidence Interval) of the hazard ratio (HR) from the Cox model 
will be presented.  
Only patients who have the Week 2 wound closure data will be analyzed. 
In addition, a sensitivity analysis will be performed using the log-rank test for the 
comparison of the two treatment groups. 
The proportional hazards assumption will be assessed by adding the treatment by time 
interaction into the Cox-proportional hazards model. If that interaction term 
approaches or reaches statistical significance, and if the Kaplan-Meier (K-M) survival 
curves indicate substantially varying treatment differences in cumulative proportion 
of patients with total wound closure, then the cumulative proportions may be 
compared between treatments for appropriate time periods suggested by the K-M 
plot. These between-treatment comparisons per time period would be via logistic 
regression or exact binomial tests. 
The consistency of the treatment effect across each of the subgroups (see Section 7.6) 
will be evaluated using descriptive statistics.  
As decided post-database lock, same analysis using K-M approach and 
Cox-proportional hazards model will be performed assuming 45 day cutoff for target 
wound closure. It means that any time to wound closure that is 44 days or more is 
going to be right censored. 
• Proportion of patients experiencing complete closure of their target wound within 
3 months 
Complete closure of the target wound will be determined at each visit. A patient will 
be considered a “responder” if they experience complete wound closure at the 
Week 2, Months 1, 2, or 3 visits. 
The proportions of “responders” (patients experiencing complete target wound 
closure within 3 months) in the two treatment groups will be compared using the 
following hypothesis testing where the null and alternate hypotheses are as follows: 
H0: P0 = P6 
Ha: P0 < P6, 
where P0 is the proportion of patients receiving Placebo experiencing the second 
primary endpoint and P6 is the proportion of patients receiving SD-101-6% 
experiencing the second primary endpoint. 
The proportion of “responders” (proportion of patients exhibiting complete closure of 
their target wound within 3 months of randomization) will be analyzed using the 
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logistic regression model with Baseline target wound size, target wound age, and EB 
type as covariates. The first analysis will be performed using the ITT population 
based on the Multiple Imputation methodology (MI) as the first imputation method 
for missing values, see Section 7.3.  
In the case that complete separation and quasi-complete separation occurs from the 
logistic regression model as specified above, the explanatory variable causing the 
situation will be identified and excluded from the model. If the treatment factor is that 
variable, then the treatment effect will be tested using the chi-square test. 
The p-value for the treatment comparison, odds ratio of response between the two 
treatment groups, and the 95% CI of the odds ratio will be presented from the logistic 
regression model. In addition, the unadjusted response rates for each group, the 
difference of unadjusted response rates between the two treatment group,s and the 
95% CI of the difference using the Miettinen-Nurminen method will also be 
provided. 
The consistency of the treatment effect across each of the subgroups (see Section 7.6) 
will be evaluated using descriptive statistics.  
8.6.1.2. 
Sensitivity Analyses 
The above primary efficacy analysis will be repeated using the PP population. Sensitivity 
analyses are considered supportive. 
To assess the robustness of the primary efficacy result, the following sensitivity analyses will be 
conducted using the ITT population: 
a. The same imputation method above will be repeated based on the Pattern-Mixture 
Model as discussed by Ratitch et al.(2) under the Missing Not at Random (MNAR) 
assumption, by using the profiles from placebo patients with observed data to impute 
missing data. 
b. Patients who withdraw early, before the confirmation of their target wound closing or 
their 3-month visit (without target wound closure), will be considered treatment 
failures with respect to the second primary endpoint. 
The treatment-by-covariate interaction will be tested in a separate model for each endpoint and 
each covariate. Sensitivity analyses will not be done for subgroups. 
8.6.2. 
Analysis of Key Secondary Efficacy Endpoints 
Formal statistical testing of the secondary efficacy endpoints will be performed after the two 
primary efficacy endpoints achieve statistical significance. To control overall Type I error rate at 
5%, the step-down strategy will be applied as described in Section 7.5. 
The covariates ie., EB type and Baseline characteristics (of the secondary endpoint being 
analyzed), will be used for the secondary analyses as they are for the primary analyses. Target 
wound age and target wound size will be used for:  
• Proportion of patients experiencing complete closure of their target wound within 
2 months 
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• Proportion of patients experiencing complete closure of their target wound within 1 
month. 
For other secondary endpoints, target wound age and target wound size will not be used as 
covariates because they are not considered effect modifiers. 
Table 3: 
Analysis Strategy for Efficacy Endpoints 
Endpoint  
Primary 
vs. 
Supportive 
Approach 
Statistical 
Method 
Analysis 
Population 
Missing 
Data 
Approach 
Two primary endpoints 
Time to complete target wound 
closure within 3 months 
P 
Cox Model 
ITT 
Censoring 
S 
Log-rank Test 
ITT 
Censoring 
S 
Cox Model 
PP 
Censoring 
S 
Log-rank Test 
PP 
Censoring 
S 
Descriptive 
Statistics 
ITT 
As observed 
Complete closure of target wound 
within 3 months 
P 
Logistic 
Regression 
ITT 
MI 
S 
Logistic 
Regression 
PP 
MI 
S 
Logistic 
Regression 
ITT 
MI (MNAR) 
S 
Logistic 
Regression 
ITT 
Missing as 
Failures 
S 
Descriptive 
Statistics 
ITT 
As observed 
Key Secondary Endpoints 
Complete closure of target wound 
within 2 months 
P 
Logistic 
Regression 
ITT 
MI 
S 
Descriptive 
Statistics 
ITT 
As observed 
Complete closure of target wound 
within 1 month 
P 
Logistic 
Regression 
ITT 
MI 
S 
Descriptive 
Statistics 
ITT 
As observed 
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Table 3: 
Analysis Strategy for Efficacy Endpoints (Continued) 
Endpoint  
Primary 
vs. 
Supportive 
Approach 
Statistical 
Method 
Analysis 
Population 
Missing 
Data 
Approach 
Change in BSAI of lesional skin at 
Month 3, compared to Baseline 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI 
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Change in BSAI of Total Body 
Wound Burden at Month 3, compared 
to Baseline 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI  
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Change in Itching assessment at Day 
7, compared to Baseline 
P 
Logistic 
Regression 
ITT 
As observed 
S 
Logistic 
Regression 
ITT 
As observed 
excluding 
missing 
S 
Descriptive 
Statistics 
ITT 
As observed  
Change in Pain assessment at Day 7, 
compared to Baseline 
P 
Logistic 
Regression 
ITT 
As observed 
S 
Logistic 
Regression 
ITT 
As observed 
excluding 
missing 
S 
Descriptive 
Statistics 
ITT 
As observed  
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Table 3: 
Analysis Strategy for Efficacy Endpoints (Continued) 
Endpoint  
Primary 
vs. 
Supportive 
Approach 
Statistical 
Method 
Analysis 
Population 
Missing 
Data 
Approach 
Other Secondary Endpoints 
Change in BSAI of Total Body 
Wound Burden at Weeks 2, Months 1 
and 2, compared to Baseline 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI 
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Percent change from Baseline in 
BSAI of Total Body Wound Burden 
at Week 2Months 1, 2, and 3 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI 
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Percent change in BSAI of lesional 
skin at Week 2, Months 1, 2, and 3, 
compared to Baseline 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI 
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
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Table 3: 
Analysis Strategy for Efficacy Endpoints (Continued) 
Endpoint  
Primary 
vs. 
Supportive 
Approach 
Statistical 
Method 
Analysis 
Population 
Missing 
Data 
Approach 
Change in BSAI of lesional skin at 
Week 2, Month 1 and Month 2, 
compared to Baseline 
P 
MMRM 
ITT 
MI 
S 
MMRM 
ITT 
As observed 
S 
ANCOVA 
ITT 
MI  
As observed 
S 
ANCOVA on 
transformed data 
ITT 
MI 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Presence of scarring of healed target 
wound at the visit where the complete 
closure is documented 
P 
Descriptive 
Statistics 
ITT with 
wound 
closure 
As observed 
Change in target wound 
characteristics (ie. milia, 
inflammation, blistering, granulation 
tissue, erythema, exudate) at Week 2, 
Months 1, 2, and 3, compared to 
Baseline 
P 
Logistic 
regression 
ITT 
As observed 
S 
Descriptive 
Statistics 
ITT 
As observed 
Change in Itching and Pain at Days 1 
to 6, Week 2, and Months 1, 2 and, 3, 
compared to Baseline 
P 
Logistic 
Regression 
ITT 
As observed 
S 
Logistic 
Regression 
ITT 
As observed 
(excluding 
missing) 
S 
Descriptive 
Statistics 
ITT 
As observed 
Target Wound Closure within Week 
2, compared to Baseline 
P 
Logistic 
Regression 
ITT 
MI 
S 
Descriptive 
Statistics 
ITT 
As observed 
Abbreviations: MMRM=Mixed model for repeated measures with treatment, visit, and visit-treatment interaction as 
fixed effects; P=Primary approach; S=Supportive approach  
The analysis of key secondary efficacy variables will be as follows: 
• Proportion of patients experiencing complete target wound closure at Month 2 
This assessment will be analyzed using the same approach as the second primary 
endpoint. 
• Proportion of patients experiencing complete target wound closure at Month 1 
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This assessment will be analyzed using the same approach as the second primary 
endpoint. 
• Change in lesional skin based on BSAI at Month 3 compared to Baseline 
For analysis, a mixed model repeated measures approach (using Restricted Maximum 
Likelihood (REML) estimation) will be used on each multiply imputed data set. The 
model will include treatment, Baseline BSAI, EB type, visit, and visit-treatment 
interaction as the fixed effects. Visit will be used as a repeated measure and an 
unstructured covariance approach will be applied. If the fit of the unstructured 
covariance structure fails to converge, the following covariance structures will be 
tried in order until convergence is reached: Toeplitz with heterogeneity, autogressive 
with heterogeneity, Toeplitz, and autoregressive. 
Means and least squares mean difference between SD-101-6% and Placebo, along 
with a two-sided 95% CI and p-value for the difference between treatments will also 
be provided. 
The following provides sample code for implementing the MMRM analysis: 
proc mixed method = reml; 
 
class TRT VISIT SUBJID;  
model <CHG>=TRT VISIT TRT*VISIT BASELINE 
EBTYPE/s ddfm=kr;  
 
 
repeated VISIT/type=UN subject=SUBJID; 
 
 
lsmeans TRT*VISIT /slice=VISIT pdiff diff alpha=0.05 cl;  
 
 
/*testing difference in treatment group level for each visit*/; 
 
run; 
where TRT is the assigned treatment, VISIT is the visit based on the window 
mapping, CHG is the change from Baseline in the BSAI measurements, EBTYPE is 
the EB type, and BASELINE is the Baseline BSAI measurements.  
In addition, the difference in changes will be presented across each of the subgroups 
(see Section 7.6) using descriptive statistics. MMRM with a subgroup factor in the 
model will be applied. In case the effects are not estimable, a simple ANCOVA 
analysis of covariance) model with EB type and Baseline BSAI measurement as 
covariates will be used with treatment and subgroup as fixed effect in the model.  
As decided post database lock, for target wound age, the following categorization will 
be used: 0 ≤ 30 days, >30 days. 
As clarified in the NTF, if any of covariates are missing, then a subject with a missing 
covariate will be excluded from the ANCOVA model. 
The above analyses will be conducted on the data after MI imputation. Analysis on 
the observed data will be conducted as a sensitivity analysis. 
A graph of the mean BSAI of lesional skin for each treatment group over time will 
also be presented. 
• Change in Total Body Wound Burden at Month 3, compared to Baseline 
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The analysis will be based on the same statistical method used for the change in BSAI 
at Month 3 of lesional skin.  
A graph of the mean Total Body Wound Burden for each treatment group over time 
will also be presented. 
• Change in itching assessed at Day 7, compared to Baseline 
As clarified in the NTF, itching scores will be categorized into three groups based on 
improvement. These groups include Improved or No Itching, Not Improved, and 
Missing, where Improved or No Itching is an itching score reduction from Baseline 
greater than or equal to 1 point on the scale or itching score of 0 at both Baseline and 
post-Baseline. The proportion of patients experiencing improvement in itching or no 
presence of itching versus non-improvement (including missing) will be compared 
between the two treatment groups for Day 7 using the same method as the second 
primary endpoint, but only with Baseline itching score, and EB type as covariates.  
It is anticipated that no patients will withdraw from the study prior to Day 7. To 
provide an analysis of the sensitivity of the conclusions resulting from the analysis of 
difference in itching scores from Baseline to Day 7, an additional analysis will be 
performed on the ITT population, but will not consider missing itching scores and 
will only compare the proportions of patients categorized as Improved or Not 
Improved. 
Descriptive statistics will be presented for two categories defined above and for the 
actual scores at Baseline and Day 7, as well as the change in itching scores from 
Baseline to Day 7. 
In addition, the consistency of the treatment effect across each of the subgroups (see 
Section 7.6) will be evaluated using descriptive statistics.  
• Change in pain assessed at Day 7, compared to Baseline 
As clarified in the NTF, similar to itching scores, pain scores will be categorized into 
three groups based on improvement. These groups include Improved, Not Improved 
or No Pain, and Missing, where Improved or No Pain is a pain score reduction from 
Baseline greater than or equal to 2 points on the scale or pain score of 0 at both 
Baseline and post-Baseline.The proportion of patients experiencing improvement in 
pain versus non-improvement (including missing) will be compared between the two 
treatment groups for Day 7 using the same method as the second primary 
endpoint,but only with Baseline pain score, and EB type as covariates. 
It is anticipated that no patients will withdraw from the study prior to Day 7. To 
provide an analysis of the sensitivity of the conclusions resulting from the analysis of 
pain at Day 7, an additional analysis will be performed on the ITT population, but 
will not consider missing pain scores and will only compare the proportions of 
patients categorized as Improved or Not Improved. 
Descriptive statistics will be presented for two categories defined above and for the 
actual scores at Baseline and Day 7, as well as the change in pain scores from 
Baseline to Day 7. 
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The treatment-by-covariate interaction will be tested in a separate model for each endpoint and 
each covariate. Subgroup means and 95% CI's will be presented as derived from this model. The 
plot of individual patient values on y-axis and covariate on x-axis, using different symbols for 
each treatment and a regression line for each treatment will be presented for continuous data.  
In addition, same analysis as above will be conducted for subgroups factors listed in Section 7.6 
keeping continuous factors as continuous (eg. patient’s age). 
In addition, the consistency of the treatment effect across each of the subgroups (see Section 7.6) 
will be evaluated using descriptive statistics.  
For continuous secondary endpoints, normality will be assessed via Shapiro-Wilk test statistics’ 
values and graphically. If suggestion of substantial departure from normality is detected, then the 
data will be transformed using log or rank transformations to yield analysis scale closest to 
normality. ANCOVA with EB type and Baseline value for the endpoint under analysis will be 
performed on transformed values. 
Supportive analyses (Table 3) will not be done for subgroups. 
8.6.3. 
Analyses of Other Secondary Endpoints 
The analysis of other secondary efficacy endpoints will be as follows: 
• Change in Total Body Wound Burden at Week 2, Months 1, and 2, compared to 
Baseline. 
•  Percent change from Baseline in Total Body Wound Burden at Week 2, Months 1, 2, 
and 3. 
• Percent change in lesional skin based on BSAI at Week 2, Months 1, 2, and 3, 
compared to Baseline 
• Change in lesional skin based on BSAI at Week 2, and Months 1 and 2, compared to 
Baseline. 
• The four endpoints listed above will be analyzed using the same approach as the 
change at Month 3 for both change from Baseline and the percentage change from 
Baseline. Although the comparison of Month 3 against Baseline is a key secondary 
endpoint, these other time points will be included in the exploration of a temporal 
pattern. Presence of scarring of healed target wound at visit of documented complete 
wound closure. 
The proportion of patients experiencing scarring will be presented for each of the two 
treatment groups only for those patients who experienced complete closure of target 
wound.  
• Change in target wound characteristics (ie. milia,inflammation, blistering, granulation 
tissue, erythema, exudate) atWeek 2, Months 1, 2, and 3, compared to Baseline.  
As clarified in the NTF, the presence of each characteristic was recorded as Yes on 
the CRF. The blank value will be considered the absence of a characteristics. The 
same approach used in the evaluation of itching and pain as key secondary endpoints 
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on observed data will be employed in the analysis of these endpoints, but will be 
performed at each of the specified visits. The categorization will be as follows: 
Baseline 
 
 
Post-baseline  
 
Category 
Absent 
 
 
Absent  
 
 
Improved or Absent 
Present 
 
 
Absent  
 
 
Improved or Absent 
Absent 
 
 
Present 
 
 
Not Improved 
Present 
 
 
Present 
 
 
Not Improved 
Assessments will be summarized using descriptive statistics at each visit by treatment 
group. A plot comparing the two treatments over time will also be presented for each 
endpoint.  
• Change in itching and pain at Days 1 to 6, Week 2, and Months 1, 2, and 3, compared 
to Baseline. 
The same approaches used in the evaluation of itching and pain as key secondary 
endpoints will be employed in the analysis of these endpoints, but will be performed 
at each of the specified visits. Assessments will be summarized using descriptive 
statistics at each visit by treatment group. A plot comparing the two treatments over 
time will also be presented for each endpoint.  
• Proportion of patients experiencing target wound closure within Week 2. 
This assessment will be analyzed independently at each visit using the same approach 
as the Month 3 primary endpoint. 
Supportive analyses will not be done for subgroups. 
8.7. 
Analysis of Safety 
8.7.1. 
Extent of Exposure and Compliance of Study Drug 
8.7.1.1. 
Extent of Exposure 
The number of days that cream is applied will be summarized using descriptive statistics by 
treatment group and overall. Descriptive statistics will also be provided for duration of exposure 
days (number of days cream applied) into categorical summary of < 14, ≥ 14 to < 30, ≥ 30 to 
< 60, ≥ 60 to < 90, ≥ 90).  
Extent of exposure will also be presented for subgroups of interest. 
8.7.1.2. 
Measurements of Treatment Compliance 
Percent compliance will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum, maximum) for < 70%, ≥ 70%, and overall by treatment group. 
8.7.2. 
Adverse Events by Preferred Term and System Organ Class 
Adverse events will be classified as treatment-emergent or non treatment-emergent.  
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A non-treatment emergent AE is defined as an AE that originated prior to the first dose of study 
drug and did not change in severity or relationship to treatment on or after the date of the first 
dose of study drug. If the severity or relationship to treatment changed on or after the first dose 
of study drug prior to the end of study, then that AE is considered a TEAE.  
For subjects entering directly into extension study SD-006, there is no follow-up period after the 
last day on study. The safety information will be entered into SD-006 database. For subjects not 
entering the extension study the SD-006, the follow-up information will be captured in the 
source documents and will not be collected in the clinical database. Serious Adverse Events 
(SAEs) will be entered into the safety database. 
8.7.3. 
Summaries of Adverse Event Incidence Rates for All Subjects 
The number and percentage of subjects who experienced TEAEs will be presented by system 
organ class (SOC) and by preferred term (PT) within SOC for each treatment group. TEAEs will 
be similarly presented by severity (mild, moderate, severe), by relationship to study drug (related 
would include definite, probable, and possible) and by outcome of events. Additionally, the 
number of TEAEs (as opposed to the number and percentage of subjects) will be presented by 
treatment group.  
Analysis will also be done for subgroups of interest. Subgroups for age are defined based on the 
subject’s age at Baseline. Details are provided in the appendices. 
To count the number of subjects who experienced each TEAE, a subject experiencing the same 
TEAE multiple times will only be counted once for the corresponding PT. Similarly, if a subject 
experiences multiple TEAEs within the same SOC, the subject will be counted only once for that 
SOC. If a subject experiencing more than one TEAE within different severity or relationship 
categories within the same SOC/PT, only the worst case (worst severity and related TEAE) will 
be reported. TEAEs will be sorted alphabetically by SOC and within each SOC the PT will be 
presented by decreasing order of total frequency.  
For TEAE summary by outcome, if a subject experienced more than one TEAE, the worst 
outcome will be counted under that subject. If a subject experienced more than one outcome 
within a SOC (or PT), the subject is only counted once under worst outcome in that SOC (or PT). 
In addition, all adverse events will be provided by study site and by treatment group, in a listing, 
which will include the subject identifier, the PT, the reported term, the severity, the seriousness, 
the action taken, the outcome, the causality, the date onset, date of onset relative to the date of 
the first study drug administration, date of resolution, date of resolution related to the first study 
drug administration, and the TEAE duration (resolution date –onset date + 1). Separate listings 
will be provided for non-treatment emergent AEs, if any.  
8.7.4. 
Missing AE Onset, Severity, and Relationship 
8.7.4.1. 
Missing or Partial AE Dates 
The following list describes how partially missing date information will be handled as it relates 
to partial or missing start dates. Partial dates will be imputed as follows: 
1. If year is not missing and is after the year of first application of study drug: 
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a. If Month is missing, then Month will be imputed as January 
b. If Day is missing, then Day will be imputed as the first of the month 
2. If year is not missing and is the same as the year of the first application of study drug: 
a. If Month is missing, then impute the Month as the month of the first application of 
study drug 
b. If Day is missing but Month is on or after the month of first application of study drug, 
then impute Day as the first day of study drug application 
c. If Day is missing but Month is on or after the month of first application of study drug, 
then impute Day as the first day of - the month. 
d. If the Day and Month are missing, then impute Day and Month as the Day and Month 
of the first study drug application. 
3. If year is missing, then impute the year as the year of the first study drug application: 
a. If Month is missing, then impute the Month as the Month of the first study drug 
application 
b. If Day is missing, then impute the Day as the day of the first study drug application 
4. If the start date is completely missing, but the AE is either ongoing or the stop date is 
after the first date of drug application, then impute the start date as the first date of study 
drug application. 
5. If using the above rules, the stop date is before the start date, then leave the stop date 
missing and assume that AE is treatment emergent for the purpose of the analysis. 
Completely missing stop dates will not be imputed. The partial stop dates will be imputed as 
follows: 
1. If the year is missing, the stop date will not be imputed 
2. If the month is missing, then the month will be imputed as December 
3. If the day is missing, then the day will be imputed as the last day of the month 
Imputed dates will be flagged in the individual supportive subject listings. 
8.7.4.2. 
Missing Severity 
If severity is missing for any AE, then its severity will be classified as missing in the summary 
tables. 
8.7.4.3. 
Missing Relationship 
If the assessment of relationship of the AE to study drug is missing for any AE, then it will be 
presented as missing in the listings and in the summary tables.  
8.7.5. 
Summaries of Adverse Event Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death 
During the treatment period, the number and percentage of subjects who experienced TESAEs 
(treatment emergent serious AEs) and separately TEAEs leading to withdrawal from the study 
will be presented by SOC and by PT within each SOC for each treatment. TESAEs and 
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separately TEAEs resulting in withdrawal from the study will be similarly presented by severity 
(mild, moderate, severe), by relationship to study drug (related would include definite, probable, 
and possible) and by outcome of events. Additionally, the number of TESAEs (as opposed to the 
number and percentage of subjects) and separately TEAEs leading to withdrawal will be 
presented. 
Subgroup analyses for gender, race, and region are performed for AEs and SAEs leading to d/c. 
Analysis will be also done for subgroups of interest. Subgroups for age are defined based on the 
subject’s age at Baseline. Details are provided in appendices. 
In case that there are non-treatment emergent adverse events observed, the number and 
percentage of patients with all SAEs will be summarized by SOC and PT within each SOC. 
Additionally, the number of SAEs (as opposed to the number and percentage of subjects) will be 
presented.  
A listing of all SAEs and discontinuations due to AEs will be included. Subject with deaths, 
SAEs, or subjects who withdraw due to AE will be listed separately and discussed with subject 
narratives.  
8.7.6. 
Discontinuation from the Study 
Number of subjects who discontinued from the study and reasons for discontinuation will be 
summarized by treatment group. 
8.7.7. 
Clinical Laboratory Evaluations 
8.7.7.1. 
Pregnancy Test 
Pregnancy test results will be listed for all female patients of child bearing potential only. 
8.7.8. 
Other Observations Related to Safety 
8.7.8.1. 
Vital Signs 
Vital signs (weight, height/length, and temperature) conducted under the physical examination 
will be summarized using descriptive statistics for both actual results and change from Baseline 
for each treatment group. Vital Signs’ assessments will also be presented in a listing. All vital 
signs will be presented using metric units. 
8.7.8.2. 
Physical Examination Findings 
Physical examination findings will be summarized in shift tables that will be presented to display 
the shift in the normal range categories (normal vs abnormal) from Baseline to the final 
evaluation. 
8.7.8.3. 
Skin Infections 
Skin infections are to be compared between treatment groups. Skin infection cluster comprises of 
the following PTs: 
• Skin infection 
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• Wound infection 
• Staphylococcal skin infection 
• Skin bacterial infection 
• Wound infection staphylococcal 
• Folliculitis 
• Wound infection bacterial 
• Cellulitis 
• Cellulitis staphylococcal 
• Impetigo 
• Infected skin ulcer 
• Postoperative wound infection 
• Rash pustular 
9. 
COMPUTER SOFTWARE 
All analyses will be performed by the designee of Scioderm using Version 9.2 or later of SAS 
software. All summary tables, data listings, and figures will be prepared utilizing SAS software. 
10. 
REFERENCES 
B. Ratitch, I. Lipkovich, and M. O’Kelly. “Combining Analysis Results from Multiply Imputed 
Categorical Data”, 2013, PharmaSUG Proceedings, Paper SP-03. 
B. Ratitch, M. O’Kelly, and R. Tosiello, “Missing Data in Clnical Trials: From Clinical 
Assumptions to Statistical Analysis Using Pattern Mixture Models”, January 2013, 
Pharmaceutical Statistics. 
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11. 
APPENDICES 
11.1. 
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 
(BSAI) 
 
 
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 
(BSAI) 
 
* 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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11.2. 
Body Surface Area Index (BSAI) of Total 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 
(BSAI) 
 
 
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 
(BSAI) 
 
 
* 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. 
 
 
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11.3 
List of Tables 
Table Number 
Table Title 
Table 14.1.1.1 
Patient Disposition  
Table 14.1.1.2 
Patient Disposition for Each Investigational Site by Country and 
Geographic Region  
Ad-hoc Table 14.1.1.3 
Patient Disposition by Age Group  
Table 14.1.2 
Demographics and Baseline Characteristics (ITT Population) 
Ad-hoc Table 14.1.2.2 
Demographics and Baseline Characteristics by Age Group 
(ITT Population) 
Ad-hoc Table 14.1.2.3 
Demographics and Baseline Characteristics by Baseline Target Wound 
Age Group (ITT Population) 
Ad-hoc Table 14.1.2.4 
Demographics and Baseline Characteristics by EB Type[1] 
(ITT Population) 
Ad-hoc Table 14.1.2.5 
Demographics and Baseline Characteristics by Baseline BSAI of Total 
Body Wound Burden Group (ITT Population) 
Table 14.1.3 
Medical History (Safety Population) 
Table 14.1.4 
Protocol Deviation (ITT Population) 
Ad-hoc Table 14.1.4.2 
Protocol Deviations (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.1.4.3 
Protocol Deviations (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.1.4.4 
Protocol Deviations (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.1.4.5 
Protocol Deviations (Baseline BSAI of Total Body Wound Burden 
>=5%) (ITT Population) 
Table 14.1.5 
Prior Medications (Safety Population) 
Ad-hoc Table 14.1.5.2 
Prior Medications (Age 2 Years to <12 Years) (Safety Population) 
Ad-hoc Table 14.1.5.3 
Prior Medications (Baseline Target Wound Age >30 Days) (Safety 
Population) 
Ad-hoc Table 14.1.5.4 
Prior Medications (Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.1.5.5 
Prior Medications (Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Table 14.1.6.1 
Concomitant Medications (Safety Population) 
Ad-hoc Table 14.1.6.1.2 
Concomitant Medications (Age 2 Years to <12 Years) (Safety 
Population) 
Ad-hoc Table 14.1.6.1.3 
Concomitant Medications (Baseline Target Wound Age >30 Days) 
(Safety Population) 
Ad-hoc Table 14.1.6.1.4 
Concomitant Medications (Recessive Dystrophic EB Type) (Safety 
Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.1.6.1.5 
Concomitant Medications (Baseline BSAI of Total Body Wound Burden 
>=5%) (Safety Population) 
Table 14.1.6.2 
Concomitant Medications of Interest (Drugs for Constipation, Vitamins 
and Mineral Supplements) (Safety Population) 
Ad-hoc Table 14.1.6.2.2 
Concomitant Medications of Interest (Age 2 Years to <12 Years) (Drugs 
for Constipation, Vitamins and Mineral Supplements) (Safety 
Population) 
Ad-hoc Table 14.1.6.2.3 
Concomitant Medications of Interest (Baseline Target Wound Age 
>30 Days) (Drugs for Constipation, Vitamins and Mineral Supplements) 
(Safety Population) 
Ad-hoc Table 14.1.6.2.4 
Concomitant Medications of Interest (Recessive Dystrophic EB Type) 
(Drugs for Constipation, Vitamins and Mineral Supplements) (Safety 
Population) 
Ad-hoc Table 14.1.6.2.5 
Concomitant Medications of Interest (Baseline BSAI of Total Body 
Wound Burden >=5%) (Drugs for Constipation, Vitamins and Mineral 
Supplements) (Safety Population) 
Table 14.1.6.3 
Concomitant Medications of Interest (Antianemic Drugs, Blood 
Substitutes and Perfusion Solutions, Antibacterial Drugs and 
Antimycotic Drugs) (Safety Population) 
Ad-hoc Table 14.1.6.3.2 
Concomitant Medications of Interest (Age 2 Years to <12 Years) 
(Antianemic Drugs, Blood Substitutes and Perfusion Solutions, 
Antibacterial Drugs and Antimycotic Drugs) (Safety Population) 
Ad-hoc Table 14.1.6.3.3 
Concomitant Medications of Interest (Baseline Target Wound Age 
>30 Days) (Antianemic Drugs, Blood Substitutes and Perfusion 
Solutions, Antibacterial Drugs and Antimycotic Drugs) (Safety 
Population) 
Ad-hoc Table 14.1.6.3.4 
Concomitant Medications of Interest (Recessive Dystrophic EB Type) 
(Antianemic Drugs, Blood Substitutes and Perfusion Solutions, 
Antibacterial Drugs and Antimycotic Drugs) (Safety Population) 
Ad-hoc Table 14.1.6.3.5 
Concomitant Medications of Interest (Baseline BSAI of Total Body 
Wound Burden >=5%) (Antianemic Drugs, Blood Substitutes and 
Perfusion Solutions, Antibacterial Drugs and Antimycotic Drugs) (Safety 
Population) 
Table 14.1.6.4 
Concomitant Medications of Interest (Analgesic Drugs, Psycholeptic 
Drugs and Psychoanaleptics) (Safety Population) 
Ad-hoc Table 14.1.6.4.2 
Concomitant Medications of Interest (Age 2 Years to <12 Years) 
(Analgesic Drugs, Psycholeptic Drugs and Psychoanaleptics) (Safety 
Population) 
Ad-hoc Table 14.1.6.4.3 
Concomitant Medications of Interest (Baseline Target Wound Age 
>30 Days) (Analgesic Drugs, Psycholeptic Drugs and Psychoanaleptics) 
(Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.1.6.4.4 
Concomitant Medications of Interest (Recessive Dystrophic EB Type) 
(Analgesic Drugs, Psycholeptic Drugs and Psychoanaleptics) (Safety 
Population) 
Ad-hoc Table 14.1.6.4.5 
Concomitant Medications of Interest (Baseline BSAI of Total Body 
Wound Burden >=5%) (Analgesic Drugs, Psycholeptic Drugs and 
Psychoanaleptics) (Safety Population) 
Table 14.1.6.5 
Concomitant Medications of Interest (Antihistamines for Systemic Use) 
(Safety Population) 
Ad-hoc Table 14.1.6.5.2 
Concomitant Medications of Interest (Age 2 Years to <12 Years) 
(Antihistamines for Systemic Use) (Safety Population) 
Ad-hoc Table 14.1.6.5.3 
Concomitant Medications of Interest (Baseline Target Wound Age 
>30 Days) (Antihistamines for Systemic Use) (Safety Population) 
Ad-hoc Table 14.1.6.5.4 
Concomitant Medications of Interest (Recessive Dystrophic EB Type) 
(Antihistamines for Systemic Use) (Safety Population) 
Ad-hoc Table 14.1.6.5.5 
Concomitant Medications of Interest (Baseline BSAI of Total Body 
Wound Burden >=5%) (Antihistamines for Systemic Use) (Safety 
Population) 
Table 14.1.6.6 
Concomitant Medications of Interest (Surgical Dressings, Medicated 
Dressings, Antiseptics and Disinfectant Drugs, Antibiotics for 
Dermatology Use, and Treatment of Wounds and Ulcers) (Safety 
Population) 
Ad-hoc Table 14.1.6.6.2 
Concomitant Medications of Interest (Age 2 Years to <12 Years) 
(Surgical Dressings, Medicated Dressings, Antiseptics and Disinfectant 
Drugs, Antibiotics for Dermatology Use, and Treatment of Wounds and 
Ulcers) (Safety Population) 
Ad-hoc Table 14.1.6.6.3 
Concomitant Medications of Interest (Baseline Target Wound Age 
>30 Days) (Surgical Dressings, Medicated Dressings, Antiseptics and 
Disinfectant Drugs, Antibiotics for Dermatology Use, and Treatment of 
Wounds and Ulcers) (Safety Population) 
Ad-hoc Table 14.1.6.6.4 
Concomitant Medications of Interest (Recessive Dystrophic EB Type) 
(Surgical Dressings, Medicated Dressings, Antiseptics and Disinfectant 
Drugs, Antibiotics for Dermatology Use, and Treatment of Wounds and 
Ulcers) (Safety Population) 
Ad-hoc Table 14.1.6.6.5 
Concomitant Medications of Interest (Baseline BSAI of Total Body 
Wound Burden >=5%) (Surgical Dressings, Medicated Dressings, 
Antiseptics and Disinfectant Drugs, Antibiotics for Dermatology Use, 
and Treatment of Wounds and Ulcers) (Safety Population) 
Table 14.1.6.7 
Concomitant Medications of Interest Available at Baseline (Topical 
Dermatological Corticosteroids, Corticosteroid Systemic, and 
Immunosuppressant Drugs) (Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.1.6.7.2 
Concomitant Medications of Interest Available at Baseline (Age 2 Years 
to <12 Years) (Topical Dermatological Corticosteroids, Corticosteroid 
Systemic, Immunosuppressant Drugs) (Safety Population) (Safety 
Population) 
Ad-hoc Table 14.1.6.7.3 
Concomitant Medications of Interest Available at Baseline (Baseline 
Target Wound Age >30 Days) (Topical Dermatological Corticosteroids, 
Corticosteroid Systemic, Immunosuppressant Drugs) (Safety Population) 
Ad-hoc Table 14.1.6.7.4 
Concomitant Medications of Interest Available at Baseline (Recessive 
Dystrophic EB Type) (Topical Dermatological Corticosteroids, 
Corticosteroid Systemic, Immunosuppressant Drugs) (Safety Population) 
Ad-hoc Table 14.1.6.7.5 
Concomitant Medications of Interest Available at Baseline (Baseline 
BSAI of Total Body Wound Burden >=5%) (Topical Dermatological 
Corticosteroids, Corticosteroid Systemic, Immunosuppressant Drugs) 
(Safety Population) 
Table 14.1.7 
Extent of Exposure (Safety Population) 
Ad-hoc Table 14.1.7.2 
Extent of Exposure (Age 2 Years to <12 Years) (Safety Population) 
Ad-hoc Table 14.1.7.3 
Extent of Exposure (Baseline Target Wound Age >30 Days) (Safety 
Population) 
Ad-hoc Table 14.1.7.4 
Extent of Exposure (Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.1.7.5 
Extent of Exposure (Baseline BSAI of Total Body Wound Burden 
>=5%) (Safety Population) 
Table 14.1.8 
Measurement of Treatment Compliance (Safety Population) 
Ad-hoc Table 14.1.8.2 
Measurement of Treatment Compliance (Age 2 Years to <12 Years) 
(Safety Population) 
Ad-hoc Table 14.1.8.3 
Measurement of Treatment Compliance (Baseline Target Wound Age 
>30 Days) (Safety Population) 
Ad-hoc Table 14.1.8.4 
Measurement of Treatment Compliance (Recessive Dystrophic EB Type) 
(Safety Population) 
Ad-hoc Table 14.1.8.5 
Measurement of Treatment Compliance (Baseline BSAI of Total Body 
Wound Burden >=5%) (Safety Population) 
Table 14.2.1 
Overview of Primary and Key Secondary Efficacy Results 
(ITT Population) 
Ad-hoc Table 14.2.1.2 
Overview of Primary and Key Secondary Efficacy Results (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.1.3 
Overview of Primary and Key Secondary Efficacy Results (Baseline 
Target Wound Age > 30 Days) (ITT Population) 
Ad-hoc Table 14.2.1.4 
Overview of Primary and Key Secondary Efficacy Results (Recessive 
Dystrophic EB Type) (ITT Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.2.1.5 
Overview of Primary and Key Secondary Efficacy Results (Baseline 
BSAI of Total Body Wound Burden >= 5%) (ITT Population) 
Ad-hoc Table 14.2.1.6 
Overview of Primary and Key Secondary Efficacy Results (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.1.7 
Overview of Primary and Key Secondary Efficacy Results (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.2.1.1 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months (ITT Population) 
Table 14.2.2.1.2 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months by Target Wound Flexural Location (ITT Population) 
Table 14.2.2.1.3 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months by Baseline Target Wound Age Group (ITT Population) 
Ad-hoc Table 14.2.2.1.4 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months by Age Group (ITT Population) 
Ad-hoc Table 14.2.2.1.5 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months by EB Type (ITT Population) 
Ad-hoc Table 14.2.2.1.6 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months by Baseline BSAI of Total Body Wound Burden Group 
(ITT Population) 
Ad-hoc Table 14.2.2.1.7 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >= 5%) (ITT Population) 
Ad-hoc Table 14.2.2.1.8 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months (Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type) (ITT Population) 
Ad-hoc Table 14.2.2.1.9 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (ITT Population) 
Ad-hoc Table 14.2.2.1.10 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.2.1.11 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.2.1.12 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.2.1.13 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.2.1.14 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >= 5%) (ITT Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.2.2.1.15 
Cox Model Analysis of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Table 14.2.2.2.1 
Log-rank Test of Time to Complete Target Wound Closure within 
3 Months (ITT Population) 
Table 14.2.2.2.2 
Log-rank Test of Time to Complete Target Wound Closure within 
3 Months by Baseline Target Wound Age Group (ITT Population) 
Ad-hoc Table 14.2.2.2.3 
Log-Rank Test of Time to Complete Target Wound Closure within 
3 Months by Age Group (ITT Population) 
Ad-hoc Table 14.2.2.2.4 
Log-Rank Test of Time to Complete Target Wound Closure within 
3 Months by EB Type (ITT Population) 
Ad-hoc Table 14.2.2.2.5 
Log-Rank Test of Time to Complete Target Wound Closure within 
3 Months by Baseline BSAI of Total Body Wound Burden Group 
(ITT Population) 
Ad-hoc Table 14.2.2.2.6 
Log-Rank Test of Time to Complete Target Wound Closure within 
3 Months (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.2.2.7 
Log-Rank Test of Time to Complete Target Wound Closure within 
3 Months (Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type) (ITT Population) 
Ad-hoc Table 14.2.2.2.8 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (ITT Population) 
Ad-hoc Table 14.2.2.2.9 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.2.2.10 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.2.2.11 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.2.2.12 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.2.2.13 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.2.2.14 
Log-Rank Test of Time to Complete Target Wound Closure within 
44 Days (Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Table 14.2.2.3 
Cox Model Analysis of Time to Complete Target Wound Closure within 
3 Months (PP Population) 
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Table Number 
Table Title 
Table 14.2.2.4 
Log-rank Test of Time to Complete Target Wound Closure within 
3 Months (PP Population) 
Table 14.2.2.5.1 
Summary of Time to Complete Target Wound Closure within 3 Months 
(ITT Population) 
Table 14.2.2.5.2 
Summary of Time to Complete Target Wound Closure within 3 Months 
by Age Group (ITT Population) 
Table 14.2.2.5.3 
Summary of Time to Complete Target Wound Closure within 3 Months 
by Target Wound Age Group (ITT Population) 
Table 14.2.2.5.4 
Summary of Time to Complete Target Wound Closure within 3 Months 
by EB Type (ITT Population) 
Ad-hoc Table 14.2.2.5.5 
Summary of Time to Complete Target Wound Closure within 3 Months 
by Baseline BSAI of Total Body Wound Burden Group (ITT Population) 
Ad-hoc Table 14.2.2.5.6 
Summary of Time to Complete Target Wound Closure within 3 Months 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.2.5.7 
Summary of Time to Complete Target Wound Closure within 3 Months 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Table 14.2.2.6 
Parameter Estimates from the Cox Model with an Added Treatment by 
Visit Interaction (ITT Population) 
Table 14.2.3.1 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months (ITT Population) 
Ad-hoc Table 14.2.3.1.2 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months by Age Group (ITT Population) 
Ad-hoc Table 14.2.3.1.3 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months by Baseline Target Wound Age Group 
(ITT Population) 
Ad-hoc Table 14.2.3.1.4 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months by EB Type (ITT Population) 
Ad-hoc Table 14.2.3.1.5 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months by Baseline BSAI of Total Body Wound 
Burden Group (ITT Population) 
Ad-hoc Table 14.2.3.1.6 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months (Age 2 Years to <12 Years and Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.3.1.7 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.2.3.1.8 
Summary of Unadjusted Response Rate for Complete Closure of Target 
Wound within 3 Months (Age 2 Years to <12 Years and Baseline Target 
Wound Age >30 Days) (ITT Population) 
Table 14.2.3.2.1 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method (ITT Population) 
Table 14.2.3.2.2 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method by Target Wound Flexural Location 
(ITT Population) 
Table 14.2.3.2.3 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method by Baseline Target Wound Age Group 
(ITT Population) 
Ad-hoc Table 14.2.3.2.4 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method by Age Group (ITT Population) 
Ad-hoc Table 14.2.3.2.5 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method by EB Type (ITT Population) 
Ad-hoc Table 14.2.3.2.6 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method by Baseline BSAI of Total Body Wound 
Burden Group (ITT Population) 
Ad-hoc Table 14.2.3.2.7 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.3.2.8 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) (ITT Population) 
Table 14.2.3.3 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI Method (PP Population) 
Table 14.2.3.4 
Logistic Regression for Complete Closure of Target Wound within 
3 Months Using MI (MNAR) Method (ITT Population) 
Table 14.2.3.5 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Missing as Failures (ITT Population) 
Table 14.2.3.6.1 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by Baseline Target Wound Size Interaction 
Using MI Method (ITT Population) 
Table 14.2.3.6.2 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by Target Wound Age Interaction Using 
MI Method (ITT Population) 
Table 14.2.3.6.3 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by EB Type Interaction Using MI Method 
(ITT Population) 
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Table Number 
Table Title 
Table 14.2.3.7.1 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by Baseline Target Wound Size Interaction 
Using MI Method (PP Population) 
Table 14.2.3.7.2 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by Target Wound Age Interaction Using MI 
Method (PP Population) 
Table 14.2.3.7.3 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by EB Type Interaction Using MI Method (PP 
Population) 
Table 14.2.3.8.1 
Logistic Regression for Complete Closure of Target Wound within 
3 Months with Treatment by Baseline Target Wound Size Interaction 
Using MI (MNAR) Method (ITT Population) 
Table 14.2.3.10 
Summary of Proportion of Target Wound Complete Closure within 
3 Months by Subgroup (ITT Population) 
Ad-hoc Table 14.2.3.10.1 
Summary of Proportion of Target Wound Complete Closure within 
2 Months by Subgroup (ITT Population) 
Ad-hoc Table 14.2.3.10.2 
Summary of Proportion of Target Wound Complete Closure within 
1 Month by Subgroup (ITT Population) 
Table 14.2.4.1.1 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (ITT Population) 
Table 14.2.4.1.2 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method by Target Wound Flexural Location 
(ITT Population) 
Table 14.2.4.1.3 
Logistic Regression for Complete Closure of Target Wound within 
2 Months with Missing as Failures (ITT Population) 
Ad-hoc Table 14.2.4.1.4 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Age 2 Years to <12 Years) 
(ITT Population) 
Ad-hoc Table 14.2.4.1.5 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.4.1.6 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.4.1.7 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.4.1.8 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.4.1.9 
Logistic Regression for Complete Closure of Target Wound within 
2 Months Using MI Method (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.4.2.1 
Logistic Regression for Complete Closure of Target Wound within 
2 Months with Treatment by Baseline Target Wound Size Interaction 
Using MI Method (ITT Population) 
Table 14.2.4.2.2 
Logistic Regression for Complete Closure of Target Wound within 
2 Months with Treatment by Target Wound Age Interaction Using 
MI Method (ITT Population) 
Table 14.2.4.2.3 
Logistic Regression for Complete Closure of Target Wound within 
2 Months with Treatment by EB Type Interaction Using MI Method 
(ITT Population) 
Table 14.2.5.1.1 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (ITT Population) 
Table 14.2.5.1.2 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method by Target Wound Flexural Location 
(ITT Population) 
Ad-hoc Table 14.2.5.1.3 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.5.1.4 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.5.1.5 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.5.1.6 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.5.1.7 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.5.1.8 
Logistic Regression for Complete Closure of Target Wound within 
1 Month Using MI Method (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.5.2.1 
Logistic Regression for Complete Closure of Target Wound within 
1 Month with Treatment by Baseline Target Wound Size Interaction 
Using MI Method (ITT Population) 
Table 14.2.5.2.2 
Logistic Regression for Complete Closure of Target Wound within 
1 Month with Treatment by Target Wound Age Interaction Using 
MI Method (ITT Population) 
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Table 14.2.5.2.3 
Logistic Regression for Complete Closure of Target Wound within 
1 Month with Treatment by EB Type Interaction Using MI Method 
(ITT Population) 
Table 14.2.6.1 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (ITT Population) 
Ad-hoc Table 14.2.6.1.2 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.6.1.3 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.6.1.4 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.6.1.5 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Baseline BSAI of Total Body Wound Burden >=5%) (ITT 
Population) 
Ad-hoc Table 14.2.6.1.6 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.6.1.7 
Summary of Absolute Value and Change in BSAI of Lesional Skin by 
Visit (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Table 14.2.6.2 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (ITT Population) 
Ad-hoc Table 14.2.6.2.2 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.6.2.3 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.6.2.4 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Recessive Dystrophic EB Type) (ITT 
Population) 
Ad-hoc Table 14.2.6.2.5 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.6.2.6 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.6.2.7 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline Using MI Method (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.6.3.1 
ANCOVA with Age Group Factor for Change in BSAI of Lesional Skin 
at Month 3 Compared to Baseline Using MI Method (ITT Population) 
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Table 14.2.6.3.2 
ANCOVA with Age of Target Wound Group Factor for Change in BSAI 
of Lesional Skin at Month 3 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.6.3.3 
ANCOVA with Baseline Target Wound Size Group Factor for Change in 
BSAI of Lesional Skin at Month 3 Compared to Baseline Using MI 
Method (ITT Population) 
Table 14.2.6.3.4 
ANCOVA with EB Type Factor for Change in BSAI of Lesional Skin at 
Month 3 Compared to Baseline Using MI Method (ITT Population) 
Table 14.2.6.3.5 
ANCOVA with Age Factor for Change in BSAI of Lesional Skin at 
Month 3 Compared to Baseline Using MI Method (ITT Population) 
Table 14.2.6.3.6 
ANCOVA with Age of Target Wound Factor for Change in BSAI of 
Lesional Skin at Month 3 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.6.4 
MMRM for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline as Observed (ITT Population) 
Table 14.2.6.6.1 
ANCOVA for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline on Log Transformed Data Using MI Method (ITT Population) 
Table 14.2.6.6.2 
ANCOVA for Change in BSAI of Lesional Skin at Month 3 Compared to 
Baseline on Rank Transformed Data Using MI Method (ITT Population) 
Table 14.2.7.1 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden Compared to Baseline by Visit (ITT Population) 
Ad-hoc Table 14.2.7.1.2 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.7.1.3 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Baseline Target Wound Age >30 Days) (ITT 
Population) 
Ad-hoc Table 14.2.7.1.4 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.7.1.5 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.7.1.6 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Age 2 Years to <12 Years and Recessive Dystrophic 
EB Type) (ITT Population) 
Ad-hoc Table 14.2.7.1.7 
Summary of Absolute Value and Change in BSAI of Total Body Wound 
Burden by Visit (Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5%) (ITT Population) 
Table 14.2.7.2 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (ITT Population) 
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Ad-hoc Table 14.2.7.2.2 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years) 
(ITT Population) 
Ad-hoc Table 14.2.7.2.3 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Baseline Target Wound Age 
>30 Days) (ITT Population) 
Ad-hoc Table 14.2.7.2.4 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Recessive Dystrophic EB 
Type) (ITT Population) 
Ad-hoc Table 14.2.7.2.5 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.7.2.6 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.7.2.7 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.7.3.2 
ANCOVA with Age Group Factor for Change in BSAI of Total Body 
Wound Burden at Month 3 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.7.3.3 
ANCOVA with Age of Target Wound Group Factor for Change in BSAI 
of Total Body Wound Burden at Month 3 Compared to Baseline Using 
MI Method (ITT Population) 
Table 14.2.7.3.4 
ANCOVA with EB Type Factor for Change in BSAI of Total Body 
Wound Burden at Month 3 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.7.3.5 
ANCOVA with Age Factor for Change in BSAI of Total Body Wound 
Burden at Month 3 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.7.3.6 
ANCOVA with Age of Target Wound Factor for Change in BSAI of 
Total Body Wound Burden at Month 3 Compared to Baseline Using 
MI Method (ITT Population) 
Table 14.2.7.4 
MMRM for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline Using Observed Data (ITT Population) 
Table 14.2.7.6.1 
ANCOVA for Change in BSAI of Total Body Wound Burden at Month 3 
Compared to Baseline on Log Transformed Data Using MI Method 
(ITT Population) 
Table 14.2.8.1.1 
Logistic Regression for Improvement in Itching Assessed at Day 7 
(Including Missing as Non-Improvement) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.8.1.2.2 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years (Including Missing as 
Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.8.1.2.3 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Baseline Target Wound Age >30 Days (Including Missing 
as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.8.1.2.4 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Recessive Dystrophic EB Type (Including Missing as 
Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.8.1.2.5 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Baseline BSAI of Total Body Wound Burden >=5% 
(Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.8.1.2.6 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type (Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.8.1.2.7 
Logistic Regression for Improvement in Itching Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5% (Including Missing as Non-Improvement) 
(ITT Population) 
Table 14.2.8.1.3.1 
Logistic Regression for Improvement in Itching Assessed at Day 7 with 
Treatment by Baseline Itching Score Interaction (Including Missing as 
Non-Improvement) 
Table 14.2.8.1.3.2 
Logistic Regression for Improvement in Itching Assessed at Day 7 with 
Treatment by EB Type Interaction (Including Missing as Non-
Improvement) 
Table 14.2.8.1.4 
Logistic Regression for Improvement in Itching Assessed at Day 7 by 
Target Wound Flexural Location (Including Missing as Non-
Improvement) 
Table 14.2.8.2.1 
Logistic Regression for Improvement in Itching Assessed at Day 7 
(Excluding Missing) (ITT Population) 
Table 14.2.8.3.1 
Summary of Improvement in Itching Assessed at Day 7 (Excluding 
Missing) (ITT Population) 
Ad-hoc Table 14.2.8.3.3 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.8.3.4 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.8.3.5 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.8.3.6 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.8.3.7 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.8.3.8 
Summary of Categorization of Change in Itching Assessed at Day 7 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.9.1.1 
Logistic Regression for Improvement in Pain Assessed at Day 7 
(Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.2 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years (Including Missing as 
Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.3 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Baseline Target Wound Age >30 Days (Including Missing 
as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.4 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Recessive Dystrophic EB Type (Including Missing as 
Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.5 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Baseline BSAI of Total Body Wound Burden >=5% 
(Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.6 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type (Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.9.1.2.7 
Logistic Regression for Improvement in Pain Assessed at Day 7 for 
Patients with Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5% (Including Missing as Non-Improvement) 
(ITT Population) 
Table 14.2.9.1.3.1 
Logistic Regression for Improvement in Pain Assessed at Day 7 with 
Treatment by Baseline Pain Score Interaction (Including Missing as 
Non-Improvement) 
Table 14.2.9.1.3.2 
Logistic Regression for Improvement in Pain Assessed at Day 7 with 
Treatment by EB Type Interaction (Including Missing as 
Non-Improvement) 
Table 14.2.9.1.4 
Logistic Regression for Improvement in Pain Assessed at Day 7 by 
Target Wound Flexural Location (Including Missing as 
Non-Improvement) 
Table 14.2.9.2.1 
Logistic Regression for Improvement in Pain Assessed at Day 7 
(Excluding Missing) (ITT Population) 
Table 14.2.9.3.1 
Summary of Improvement in Pain Assessed at Day 7 (Excluding 
Missing) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.9.3.3 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.9.3.4 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.9.3.5 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.9.3.6 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.9.3.7 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) (ITT 
Population) 
Ad-hoc Table 14.2.9.3.8 
Summary of Categorization of Change in Pain Assessed at Day 7 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.10.1 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (ITT 
Population) 
Ad-hoc Table 14.2.10.1.2 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Age 2 Years to 
<12 Years) (ITT Population) 
Ad-hoc Table 14.2.10.1.3 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.10.1.4 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.10.1.5 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.10.1.6 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.10.1.7 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline Using MI Method (Age 2 to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.10.2.1 
ANCOVA with Age Group Factor for Change in BSAI of Total Body 
Wound Burden at Week 2, Months 1 and 2 Compared to Baseline Using 
MI Method (ITT Population) 
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Table 14.2.10.2.2 
ANCOVA with Age of Target Wound Group Factor for Change in BSAI 
of Total Body Wound Burden at Week 2, Months 1 and 2 Compared to 
Baseline Using MI Method (ITT Population) 
Table 14.2.10.2.3 
ANCOVA with EB Type Factor for Change in BSAI of Total Body 
Wound Burden at Week 2, Months 1 and 2 Compared to Baseline Using 
MI Method (ITT Population) 
Table 14.2.10.3 
MMRM for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline as Observed (ITT Population) 
Table 14.2.10.5.1 
ANCOVA for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline on Log Transformed Data Using 
MI Method (ITT Population) 
Table 14.2.10.5.2 
ANCOVA for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline on Rank Transformed Data Using 
MI Method (ITT Population) 
Table 14.2.10.6.1 
ANCOVA for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline on Log Transformed Data as 
Observed (ITT Population) 
Table 14.2.10.6.2 
ANCOVA for Change in BSAI of Total Body Wound Burden at Week 2, 
Months 1 and 2 Compared to Baseline on Rank Transformed Data as 
Observed (ITT Population) 
Table 14.2.11.1 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Using MI Method 
(ITT Population) 
Ad-hoc Table 14.2.11.1.2 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.11.1.3 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.11.1.4 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.11.1.5 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.11.1.6 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Age 2 Years to <12 Years and Recessive Dystrophic 
EB Type) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.11.1.7 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 Compared to Baseline 
Using MI Method (Age 2 Years to <12 Years and Baseline BSAI of 
Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.11.2.1 
ANCOVA with Age Group Factor for Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Week 2, Months 1, 2 and 3 Using 
MI Method (ITT Population) 
Table 14.2.11.2.2 
ANCOVA with Age of Target Wound Group Factor for Percent Change 
from Baseline in BSAI of Total Body Wound Burden at Week 2, Months 
1, 2 and 3 Using MI Method (ITT Population) 
Table 14.2.11.2.3 
ANCOVA with EB Type Factor for Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Week 2, Months 1, 2 and 3 Using 
MI Method (ITT Population) 
Table 14.2.11.3 
MMRM for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 as Observed 
(ITT Population) 
Table 14.2.11.5.1 
ANCOVA for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 on Log Transformed Data 
Using MI Method (ITT Population) 
Table 14.2.11.5.2 
ANCOVA for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 on Rank Transformed Data 
Using MI Method (ITT Population) 
Table 14.2.11.6.1 
ANCOVA for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 on Log Transformed Data 
as Observed (ITT Population) 
Table 14.2.11.6.2 
ANCOVA for Percent Change from Baseline in BSAI of Total Body 
Wound Burden at Week 2, Months 1, 2 and 3 on Rank Transformed Data 
as Observed (ITT Population) 
Table 14.2.11.7 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (ITT Population) 
Ad-hoc Table 14.2.11.7.2 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.11.7.3 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.11.7.4 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.11.7.5 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Baseline BSAI of Total Body Wound Burden 
>=5%) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.11.7.6 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.11.7.7 
Summary of Absolute Value and Percent Change in BSAI of Total Body 
Wound Burden by Visit (Age 2 Years to <12 Years and Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.2.12.1 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (ITT 
Population) 
Ad-hoc Table 14.2.12.1.2 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.12.1.3 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.12.1.4 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.12.1.5 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.12.1.6 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.12.1.7 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline Using MI Method (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Table 14.2.12.2.1 
ANCOVA with Age Group Factor for Percent Change in BSAI of 
Lesional Skin at Week 2, Months 1, 2 and 3 Compared to Baseline Using 
MI Method (ITT Population) 
Table 14.2.12.2.2 
ANCOVA with Age of Target Wound Group Factor for Percent Change 
in BSAI of Lesional Skin at Week 2, Months 1, 2 and 3 Compared to 
Baseline Using MI Method (ITT Population) 
Table 14.2.12.2.3 
ANCOVA with EB Type Factor for Percent Change in BSAI of Lesional 
Skin at Week 2, Months 1, 2 and 3 Compared to Baseline Using MI 
Method (ITT Population) 
Table 14.2.12.3 
MMRM for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline as Observed (ITT Population) 
Table 14.2.12.5.1 
ANCOVA for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline on Log Transformed Data 
Using MI Method (ITT Population) 
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Table 14.2.12.5.2 
ANCOVA for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline on Rank Transformed Data 
Using MI Method (ITT Population) 
Table 14.2.12.6.1 
ANCOVA for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline on Log Transformed Data as 
Observed (ITT Population) 
Table 14.2.12.6.2 
ANCOVA for Percent Change in BSAI of Lesional Skin at Week 2, 
Months 1, 2 and 3 Compared to Baseline on Rank Transformed Data as 
Observed (ITT Population) 
Table 14.2.12.7 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (ITT Population) 
Ad-hoc Table 14.2.12.7.2 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.12.7.3 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.12.7.4 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.12.7.5 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Table 14.2.12.7.6 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.12.7.7 
Summary of Absolute Value and Percent Change in BSAI of Lesional 
Skin by Visit (Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type) (ITT Population) 
Table 14.2.13.1 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (ITT Population) 
Ad-hoc Table 14.2.13.1.2 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Age 2 Years to <12 Years) 
(ITT Population) 
Ad-hoc Table 14.2.13.1.3 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Baseline Target Wound Age 
>30 Days) (ITT Population) 
Ad-hoc Table 14.2.13.1.4 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Recessive Dystrophic EB 
Type) (ITT Population) 
Ad-hoc Table 14.2.13.1.5 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Baseline BSAI of Total 
Body Wound Burden >=5%) (ITT Population) 
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Ad-hoc Table 14.2.13.1.6 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Age 2 Years to <12 Years 
and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.13.1.7 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline Using MI Method (Age 2 Years to <12 Years 
and Baseline BSAI of Total Body Wound Burden >=5%) (ITT 
Population) 
Table 14.2.13.2.1 
ANCOVA with Age Group Factor for Change in BSAI of Lesional Skin 
at Week 2, Months 1 and 2 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.13.2.2 
ANCOVA with Age of Target Wound Group Factor for Change in BSAI 
of Lesional Skin at Week 2, Months 1 and 2 Compared to Baseline Using 
MI Method (ITT Population) 
Table 14.2.13.2.3 
ANCOVA with EB Type Factor for Change in BSAI of Lesional Skin at 
Week 2, Months 1 and 2 Compared to Baseline Using MI Method 
(ITT Population) 
Table 14.2.13.3 
MMRM for Change in BSAI of Lesional Skin at Week 2, Months 1 and 
2 Compared to Baseline as Observed (ITT Population) 
Table 14.2.13.5.1 
ANCOVA for Change in BSAI of Lesional Skin at Week 2, Months 1 
and 2 Compared to Baseline on Log Transformed Data Using MI Method 
(ITT Population) 
Table 14.2.13.5.2 
ANCOVA for Change in BSAI of Lesional Skin at Week 2, Months 1 
and 2 Compared to Baseline on Rank Transformed Data Using MI 
Method (ITT Population) 
Table 14.2.13.6.1 
ANCOVA for Change in BSAI of Lesional Skin at Week 2, Months 1 
and 2 Compared to Baseline on Log Transformed Data as Observed 
(ITT Population) 
Table 14.2.13.6.2 
ANCOVA for Change in BSAI of Lesional Skin at Week 2, Months 1 
and 2 Compared to Baseline on Rank Transformed Data as Observed 
(ITT Population) 
Table 14.2.14 
Summary of Scarring of Healed Target Wound (ITT Population with 
Target Wound Closure Patients) 
Ad-hoc Table 14.2.14.2 
Summary of Scarring of Healed Target Wound (Age 2 Years to 
<12 Years) (ITT Population with Target Wound Closure Patients) 
Ad-hoc Table 14.2.14.3 
Summary of Scarring of Healed Target Wound (Baseline Target Wound 
Age >30 Days) (ITT Population with Target Wound Closure Patients) 
Ad-hoc Table 14.2.14.4 
Summary of Scarring of Healed Target Wound (Recessive Dystrophic 
EB Type) (ITT Population with Target Wound Closure Patients) 
Ad-hoc Table 14.2.14.5 
Summary of Scarring of Healed Target Wound (Baseline BSAI of Total 
Body Wound Burden >=5%) (ITT Population with Target Wound 
Closure Patients) 
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Ad-hoc Table 14.2.14.6 
Summary of Scarring of Healed Target Wound (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (ITT Population with 
Target Wound Closure Patients) 
Ad-hoc Table 14.2.14.7 
Summary of Scarring of Healed Target Wound (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population with Target Wound Closure Patients) 
Table 14.2.15.1.1 
Summary of Change in Target Wound Inflammation by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.1.1.2 Summary of Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.1.1.3 Summary of Change in Target Wound Inflammation by Visit (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.1.1.4 Summary of Change in Target Wound Inflammation by Visit (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.1.1.5 Summary of Change in Target Wound Inflammation by Visit (Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.1.1.6 Summary of Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.15.1.1.7 Summary of Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) 
Table 14.2.15.1.2 
Logistic Regression for Change in Target Wound Inflammation by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.1.2.2 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.1.2.3 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.1.2.4 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.1.2.5 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.1.2.6 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.15.1.2.7 Logistic Regression for Change in Target Wound Inflammation by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.15.2.1 
Summary of Change in Target Wound Blistering by Visit 
(ITT Population) 
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Ad-hoc Table 14.2.15.2.1.2 Summary of Change in Target Wound Blistering by Visit (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.2.1.3 Summary of Change in Target Wound Blistering by Visit (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.2.1.4 Summary of Change in Target Wound Blistering by Visit (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.2.1.5 Summary of Change in Target Wound Blistering by Visit (Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.2.1.6 Summary of Change in Target Wound Blistering by Visit (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.2.1.7 Summary of Change in Target Wound Blistering by Visit (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.15.2.2 
Logistic Regression for Change in Target Wound Blistering by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.2.2.2 Logistic Regression for Change in Target Wound Blistering by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.2.2.3 Logistic Regression for Change in Target Wound Blistering by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.2.2.4 Logistic Regression for Change in Target Wound Blistering by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.2.2.5 Logistic Regression for Change in Target Wound Blistering by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.2.2.6 Logistic Regression for Change in Target Wound Blistering by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.15.2.2.7 Logistic Regression for Change in Target Wound Blistering by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.15.3.1 
Summary of Change in Target Wound Milia by Visit (ITT Population) 
Ad-hoc Table 14.2.15.3.1.2 Summary of Change in Target Wound Milia by Visit (Age 2 Years to 
<12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.3.1.3 Summary of Change in Target Wound Milia by Visit (Baseline Target 
Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.3.1.4 Summary of Change in Target Wound Milia by Visit (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.3.1.5 Summary of Change in Target Wound Milia by Visit (Baseline BSAI of 
Total Body Wound Burden >=5%) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.15.3.1.6 Summary of Change in Target Wound Milia by Visit (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.3.1.7 Summary of Change in Target Wound Milia by Visit (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.15.3.2 
Logistic Regression for Change in Target Wound Milia by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.3.2.2 Logistic Regression for Change in Target Wound Milia by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.3.2.3 Logistic Regression for Change in Target Wound Milia by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.3.2.4 Logistic Regression for Change in Target Wound Milia by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.3.2.5 Logistic Regression for Change in Target Wound Milia by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.3.2.6 Logistic Regression for Change in Target Wound Milia by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.15.3.2.7 Logistic Regression for Change in Target Wound Milia by Visit 
(Age 2 Years to <12 Year and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.15.4.1 
Summary of Change in Target Wound Erythema by Visit (ITT 
Population) 
Ad-hoc Table 14.2.15.4.1.2 Summary of Change in Target Wound Erythema by Visit (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.4.1.3 Summary of Change in Target Wound Erythema by Visit (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.4.1.4 Summary of Change in Target Wound Erythema by Visit (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.4.1.5 Summary of Change in Target Wound Erythema by Visit (Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.4.1.6 Summary of Change in Target Wound Erythema by Visit (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.4.1.7 Summary of Change in Target Wound Erythema by Visit (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.15.4.2 
Logistic Regression for Change in Target Wound Erythema by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.4.2.2 Logistic Regression for Change in Target Wound Erythema by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.15.4.2.3 Logistic Regression for Change in Target Wound Erythema by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.4.2.4 Logistic Regression for Change in Target Wound Erythema by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.4.2.5 Logistic Regression for Change in Target Wound Erythema by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.4.2.6 Logistic Regression for Change in Target Wound Erythema by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.4.2.7 Logistic Regression for Change in Target Wound Erythema by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Table 14.2.15.5.1 
Summary of Change in Target Wound Exudate by Visit (ITT Population) 
Ad-hoc Table 14.2.15.5.1.2 Summary of Change in Target Wound Exudate by Visit (Age 2 Years to 
<12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.5.1.3 Summary of Change in Target Wound Exudate by Visit (Baseline Target 
Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.5.1.4 Summary of Change in Target Wound Exudate by Visit (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.5.1.5 Summary of Change in Target Wound Exudate by Visit (Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.5.1.6 Summary of Change in Target Wound Exudate by Visit (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.5.1.7 Summary of Change in Target Wound Exudate by Visit (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.15.5.2 
Logistic Regression for Change in Target Wound Exudate by Visit 
(ITT Population) 
Ad-hoc Table 14.2.15.5.2.2 Logistic Regression for Change in Target Wound Exudate by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.15.5.2.3 Logistic Regression for Change in Target Wound Exudate by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.15.5.2.4 Logistic Regression for Change in Target Wound Exudate by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.15.5.2.5 Logistic Regression for Change in Target Wound Exudate by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.15.5.2.6 Logistic Regression for Change in Target Wound Exudate by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
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Table Title 
Ad-hoc Table 14.2.15.5.2.7 Logistic Regression for Change in Target Wound Exudate by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Table 14.2.16.1.1 
Logistic Regression for Improvement in Itching over Time (Including 
Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.1.1.2 Logistic Regression for Improvement in Itching over Time for Patients 
with Age 2 Years to <12 Years (Including Missing as Non-Improvement) 
(ITT Population) 
Ad-hoc Table 14.2.16.1.1.3 Logistic Regression for Improvement in Itching over Time for Patients 
with Baseline Target Wound Age >30 Days (Including Missing as 
Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.1.1.4 Logistic Regression for Improvement in Itching over Time for Patients 
with Recessive Dystrophic EB Type (Including Missing as Non-
Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.1.1.5 Logistic Regression for Improvement in Itching over Time for Patients 
with Baseline BSAI of Total Body Wound Burden >=5% (Including 
Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.1.1.6 Logistic Regression for Improvement in Itching over Time for Patients 
with Age 2 Years to <12 Years and Recessive Dystrophic EB Type 
(Including Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.1.1.7 Logistic Regression for Improvement in Itching over Time for Patients 
with Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5% (Including Missing as Non-Improvement) (ITT 
Population) 
Table 14.2.16.1.2 
Logistic Regression for Improvement in Itching over Time (Excluding 
Missing) (ITT Population) 
Table 14.2.16.1.3 
Summary of Improvement in Itching over Time (Excluding Missing) 
(ITT Population) 
Ad-hoc Table 14.2.16.1.3.2 Summary of Improvement in Itching over Time (Age 2 Years to 
<12 Years) (ITT Population) 
Ad-hoc Table 14.2.16.1.3.3 Summary of Improvement in Itching over Time (Baseline Target Wound 
Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.16.1.3.4 Summary of Improvement in Itching over Time (Recessive Dystrophic 
EB Type) (ITT Population) 
Ad-hoc Table 14.2.16.1.3.5 Summary of Improvement in Itching over Time (Baseline BSAI of Total 
Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.16.1.3.6 Summary of Improvement in Itching over Time (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.16.1.3.7 Summary of Improvement in Itching over Time (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
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Table 14.2.16.2.1 
Logistic Regression for Improvement in Pain over Time (Including 
Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.2.1.2 Logistic Regression for Improvement in Pain over Time for Patients with 
Age 2 Years to <12 Years (Including Missing as Non-Improvement) 
(ITT Population) 
Ad-hoc Table 14.2.16.2.1.3 Logistic Regression for Improvement in Pain over Time for Patients with 
Baseline Target Wound Age >30 Days (Including Missing as Non-
Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.2.1.4 Logistic Regression for Improvement in Pain over Time for Patients with 
Recessive Dystrophic EB Type (Including Missing as Non-
Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.2.1.5 Logistic Regression for Improvement in Pain over Time for Patients with 
Baseline BSAI of Total Body Wound Burden >=5% (Including Missing 
as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.2.1.6 Logistic Regression for Improvement in Pain over Time for Patients with 
Age 2 Years to <12 Years and Recessive Dystrophic EB Type (Including 
Missing as Non-Improvement) (ITT Population) 
Ad-hoc Table 14.2.16.2.1.7 Logistic Regression for Improvement in Pain over Time for Patients with 
Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%(Including Missing as Non-Improvement) (ITT Population) 
Table 14.2.16.2.2 
Logistic Regression for Improvement in Pain over Time (Excluding 
Missing) (ITT Population) 
Table 14.2.16.2.3 
Summary of Improvement in Pain over Time (Excluding Missing) 
(ITT Population) 
Ad-hoc Table 14.2.16.2.3.2 Summary of Categorization of Change in Pain over Time (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.16.2.3.3 Summary of Categorization of Change in Pain over Time (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.16.2.3.4 Summary of Categorization of Change in Pain over Time (Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.16.2.3.5 Summary of Categorization of Change in Pain over Time (Baseline BSAI 
of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.16.2.3.6 Summary of Categorization of Change in Pain over Time (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.16.2.3.7 Summary of Categorization of Change in Pain over Time (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Table 14.2.17 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (ITT Population) 
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Table Title 
Ad-hoc Table 14.2.17.2 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.17.3 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.17.4 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.17.5 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.17.6 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.17.7 
Logistic Regression for Complete Closure of Target Wound within 
2 Weeks Using MI Method (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.18.1 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(ITT Population) 
Ad-hoc Table 14.2.18.1.2 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Age 2 Years to <12 Years) (ITT Population) 
Ad-hoc Table 14.2.18.1.3 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Baseline Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Table 14.2.18.1.4 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.18.1.5 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.18.1.6 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Table 14.2.18.1.7 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.18.1.8 
Summary of Absolute Value and Change in Target Wound Size by Visit 
(Age 2 Years to <12 Years and Baseline Target Wound Age >30 Days) 
(ITT Population) 
Ad-hoc Table 14.2.18.2 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (ITT Population) 
Ad-hoc Table 14.2.18.2.2 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years) 
(ITT Population) 
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Table Title 
Ad-hoc Table 14.2.18.2.3 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Baseline Target Wound Age 
>30 Days) (ITT Population) 
Ad-hoc Table 14.2.18.2.4 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Recessive Dystrophic EB 
Type) (ITT Population) 
Ad-hoc Table 14.2.18.2.5 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Ad-hoc Table 14.2.18.2.6 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (ITT Population) 
Ad-hoc Table 14.2.18.2.7 
MMRM for Change in Target Wound Size at Week 2, Month 1, 2 and 3 
Compared to Baseline Using MI Method (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Table 14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events (Safety 
Population) 
Ad-hoc Table 14.3.1.1.2 
Overall Summary of Treatment-Emergent Adverse Events (Age 2 Years 
to <12 Years) (Safety Population) 
Ad-hoc Table 14.3.1.1.3 
Overall Summary of Treatment-Emergent Adverse Events (Baseline 
Target Wound Age >30 Days) (Safety Population) 
Ad-hoc Table 14.3.1.1.4 
Overall Summary of Treatment-Emergent Adverse Events (Recessive 
Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.1.5 
Overall Summary of Treatment-Emergent Adverse Events (Baseline 
BSAI of Total Body Wound Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.1.6 
Overall Summary of Treatment-Emergent Adverse Events (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.1.7 
Overall Summary of Treatment-Emergent Adverse Events (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Table 14.3.1.2.1 
Incidence of Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term (Safety Population) 
Table 14.3.1.2.2 
Number of Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term (Safety Population) 
Table 14.3.1.3.1 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.3.2 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.3.1.3.3.1 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years) (Safety 
Population) 
Ad-hoc Table 14.3.1.3.3.2 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Baseline Target Wound Age >30 Days) 
(Safety Population) 
Ad-hoc Table 14.3.1.3.3.3 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Recessive Dystrophic EB Type) 
(Safety Population) 
Ad-hoc Table 14.3.1.3.3.4 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Baseline BSAI of Total Body Wound 
Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.3.3.5 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.3.3.6 
Incidence of Treatment-Emergent Adverse Events by Severity, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.3.4.1 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Age 2 Years to <12 Years) (Safety Population) 
Ad-hoc Table 14.3.1.3.4.2 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Baseline Target Wound Age >30 Days) (Safety Population) 
Ad-hoc Table 14.3.1.3.4.3 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.3.4.4 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Baseline BSAI of Total Body Wound Burden >=5%) (Safety 
Population) 
Ad-hoc Table 14.3.1.3.4.5 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(Safety Population) 
Ad-hoc Table 14.3.1.3.4.6 
Summary of Number of Treatment-Emergent Adverse Events by 
Severity (Age 2 Years to <12 Years and Baseline BSAI of Total Body 
Wound Burden >=5%) (Safety Population) 
Table 14.3.1.4.1 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.4.2 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Safety Population) 
Ad-hoc Table 14.3.1.4.3.1 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Age 2 Years to 
<12 Years) (Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.3.1.4.3.2 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Baseline Target 
Wound Age >30 Days) (Safety Population) 
Ad-hoc Table 14.3.1.4.3.3 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Recessive 
Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.4.3.4 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Baseline BSAI of 
Total Body Wound Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.4.3.5 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.4.3.6 
Incidence of Treatment-Emergent Adverse Events by Relationship to 
Study Drug, System Organ Class and Preferred Term (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Ad-hoc Table 14.3.1.4.4.1 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years) (Safety 
Population) 
Ad-hoc Table 14.3.1.4.4.2 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Baseline Target Wound Age >30 Days) 
(Safety Population) 
Ad-hoc Table 14.3.1.4.4.3 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Recessive Dystrophic EB Type) 
(Safety Population) 
Ad-hoc Table 14.3.1.4.4.4 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Baseline BSAI of Total Body Wound 
Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.4.4.5 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.4.4.6 
Number of Treatment-Emergent Adverse Events by Relationship, System 
Organ Class and Preferred Term (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (Safety Population) 
Table 14.3.1.5 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class and Preferred Term (Safety Population) 
Ad-hoc Table 14.3.1.5.2 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Age 2 Years to <12 Years) (Safety 
Population) 
Ad-hoc Table 14.3.1.5.3 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Baseline Target Wound Age >30 Days) 
(Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.3.1.5.4 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Recessive Dystrophic EB Type) (Safety 
Population) 
Ad-hoc Table 14.3.1.5.5 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Baseline BSAI of Total Body Wound 
Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.1.5.6 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.5.7 
Incidence of Treatment-Emergent Adverse Events by Outcome, System 
Organ Class, Preferred Term (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (Safety Population) 
Table 14.3.1.6.2.1 
Incidence of Treatment-Emergent Adverse Events by Age Group, 
System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.2.2 
Number of Treatment-Emergent Adverse Events by Age Group, System 
Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.3.1 
Incidence of Treatment-Emergent Adverse Events by Target Wound Age 
Group, System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.3.2 
Number of Treatment-Emergent Adverse Events by Target Wound Age 
Group, System Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.6.1 
Incidence of Treatment-Emergent Adverse Events by EB Type, System 
Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.6.2 
Number of Treatment-Emergent Adverse Events by EB Type, System 
Organ Class and Preferred Term (Safety Population) 
Table 14.3.1.6.7.1 
Incidence of Treatment-Emergent Adverse Events by Baseline BSAI of 
Total Body Wound Burden Group, System Organ Class and Preferred 
Term (Safety Population) 
Table 14.3.1.6.7.2 
Number of Treatment-Emergent Adverse Events by Baseline BSAI of 
Total Body Wound Burden Group, System Organ Class and Preferred 
Term (Safety Population) 
Table 14.3.1.7.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety 
Population) 
Table 14.3.1.7.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety 
Population) 
Table 14.3.1.8.1 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety 
Population) 
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Table Number 
Table Title 
Table 14.3.1.8.2 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by System Organ Class and Preferred Term (Safety 
Population) 
Table 14.3.1.9.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Maximum Severity, System Organ Class and 
Preferred Term 
Table 14.3.1.9.2 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Maximum Severity, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.10.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Relationship to Study Drug, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.10.2 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Relationship to Study Drug, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.11.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Outcome, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.11.2 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Outcome, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.1.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Gender, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.1.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Gender, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.1.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Gender, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.1.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Gender, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.2.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Age Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.2.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Age Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.2.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Age Group, System Organ Class and Preferred Term 
(Safety Population) 
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Table Number 
Table Title 
Table 14.3.1.12.2.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Age Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.3.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Target Wound Age Group, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.3.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Target Wound Age Group, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.3.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Target Wound Age Group, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.3.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Target Wound Age Group, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.4.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Race Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.4.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Race Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.4.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Race Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.4.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Race Group, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.5.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Baseline Target Wound Size Group, System Organ 
Class and Preferred Term (Safety Population) 
Table 14.3.1.12.5.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Baseline Target Wound Size Group, System Organ 
Class and Preferred Term (Safety Population) 
Table 14.3.1.12.5.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Baseline Target Wound Size Group, System Organ 
Class and Preferred Term (Safety Population) 
Table 14.3.1.12.5.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Baseline Target Wound Size Group, System Organ 
Class and Preferred Term (Safety Population) 
Table 14.3.1.12.6.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by EB Type, System Organ Class and Preferred Term 
(Safety Population) 
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Table Number 
Table Title 
Table 14.3.1.12.6.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by EB Type, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.6.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by EB Type, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.6.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by EB Type, System Organ Class and Preferred Term 
(Safety Population) 
Table 14.3.1.12.7.1 
Incidence of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Geographic Region, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.7.2 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation by Geographic Region, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.7.3 
Incidence of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Geographic Region, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.12.7.4 
Number of Treatment-Emergent Serious Adverse Events Leading to 
Discontinuation by Geographic Region, System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.13.1 
Incidence of All Serious Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
Table 14.3.1.13.2 
Number of All Serious Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
Ad-hoc Table 14.3.1.13.3.1 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years) (Safety Population) 
Ad-hoc Table 14.3.1.13.3.2 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Baseline Target Wound Age >30 Days) (Safety 
Population) 
Ad-hoc Table 14.3.1.13.3.3 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.13.3.4 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Ad-hoc Table 14.3.1.13.3.5 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type) (Safety Population) 
Ad-hoc Table 14.3.1.13.3.6 Incidence of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5%) (Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.3.1.13.4.1 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years) (Safety Population) 
Ad-hoc Table 14.3.1.13.4.2 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Baseline Target Wound Age >30 Days) (Safety 
Population) 
Ad-hoc Table 14.3.1.13.4.3 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Recessive Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.1.13.4.4 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Ad-hoc Table 14.3.1.13.4.5 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years and Recessive Dystrophic EB 
Type) (Safety Population) 
Ad-hoc Table 14.3.1.13.4.6 Number of All Serious Adverse Events by System Organ Class, 
Preferred Term (Age 2 Years to <12 Years and Baseline BSAI of Total 
Body Wound Burden >=5%) (Safety Population) 
Table 14.3.1.14 
Incidence of Treatment-Emergent Adverse Events Leading to Death by 
Preferred Term (Safety Population) 
Table 14.3.3.1 
Summary of Vital Signs (Safety Population) 
Table 14.3.4 
Shift Tables of Physical Examination Results from Baseline (Safety 
Population) 
Ad-hoc Table 14.3.5.1.1 
Summary of Skin Infection (Safety Population) 
Ad-hoc Table 14.3.5.1.2 
Summary of Number of Episodes of Skin Infection (Safety Population) 
Ad-hoc Table 14.3.5.2.1 
Summary of Skin Infection (Age 2 Years to <12 Years) (Safety 
Population) 
Ad-hoc Table 14.3.5.2.2 
Summary of Number of Episodes of Skin Infection (Age 2 Years to <12 
Years) (Safety Population) 
Ad-hoc Table 14.3.5.3.1 
Summary of Skin Infection (Baseline Target Wound Age >30 Days) 
(Safety Population) 
Ad-hoc Table 14.3.5.3.2 
Summary of Number of Episodes of Skin Infection (Baseline Target 
Wound Age >30 Days) (Safety Population) 
Ad-hoc Table 14.3.5.4.1 
Summary of Skin Infection (Recessive Dystrophic EB Type) (Safety 
Population) 
Ad-hoc Table 14.3.5.4.2 
Summary of Number of Episodes of Skin Infection (Recessive 
Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.5.5.1 
Summary of Skin Infection (Baseline BSAI of Total Body Wound 
Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.5.5.2 
Summary of Number of Episodes of Skin Infection (Baseline BSAI of 
Total Body Wound Burden >=5%) (Safety Population) 
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Table Number 
Table Title 
Ad-hoc Table 14.3.5.6.1 
Summary of Skin Infection (Age 2 Years to <12 Years and Baseline 
BSAI of Total Body Wound Burden >=5%) (Safety Population) 
Ad-hoc Table 14.3.5.6.2 
Summary of Number of Episodes of Skin Infection (Age 2 Years to 
<12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(Safety Population) 
Ad-hoc Table 14.3.5.7.1 
Summary of Skin Infection (Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type) (Safety Population) 
Ad-hoc Table 14.3.5.7.2 
Summary of Number of Episodes of Skin Infection (Age 2 Years to 
<12 Years and Recessive Dystrophic EB Type) (Safety Population) 
11.4 
List of Figures 
Figure Number 
Figure Title 
Figure 14.2.2.1 
Kaplan-Meier Curve for Target Wound Closure within 3 Months 
(ITT Population)  
Figure 14.2.2.2 
Kaplan-Meier Curve for Target Wound Closure within 3 Months 
(PP Population)  
Figure 14.2.2.3 
Complete Target Wound Closure over Time (ITT Population)  
Ad-hoc Figure 14.2.2.4 
Kaplan-Meier Curve for Target Wound Closure within 3 Months by 
Age Group (ITT Population)  
Ad-hoc Figure 14.2.2.5 
Kaplan-Meier Curve for Target Wound Closure within 3 Months by 
Baseline BSAI of Total Body Wound Burden Group (ITT Population)  
Ad-hoc Figure 14.2.2.6 
Kaplan-Meier Curve for Target Wound Closure within 3 Months 
(Age 2 Years to <12 Years and Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population)  
Ad-hoc Figure 14.2.2.7 
Kaplan-Meier Curve for Target Wound Closure within 3 Months 
(Age 2 Years to <12 Years and Recessive Dystrophic EB Type) 
(ITT Population)  
Ad-hoc Figure 14.2.2.8 
Kaplan-Meier Curve for Target Wound Closure within 3 Months by EB 
Type (ITT Population)  
Ad-hoc Figure 14.2.2.9 
Kaplan-Meier Curve for Target Wound Closure within 3 Months by 
Baseline Target Wound Age Group (ITT Population)  
Ad-hoc Figure 14.2.2.10 
Kaplan-Meier Curve for Target Wound Closure within 44 Days (ITT 
Population)  
Ad-hoc Figure 14.2.2.11 
Kaplan-Meier Curve for Target Wound Closure within 44 Days (Age 2 
Years to <12 Years and Baseline BSAI of Total Body Wound Burden 
>=5%) (ITT Population)  
Ad-hoc Figure 14.2.2.12 
Kaplan-Meier Curve for Target Wound Closure within 44 Days (Age 2 
Years to <12 Years and Recessive Dystrophic EB Type) (ITT 
Population)  
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Figure Number 
Figure Title 
Ad-hoc Figure 14.2.2.13 
Kaplan-Meier Curve for Target Wound Closure within 44 Days 
(Age 2 Years to <12 Years) (ITT Population)  
Ad-hoc Figure 14.2.2.14 
Kaplan-Meier Curve for Target Wound Closure within 44 Days 
(Baseline Target Wound Age >30 Days) (ITT Population)  
Ad-hoc Figure 14.2.2.15 
Kaplan-Meier Curve for Target Wound Closure within 44 Days 
(Recessive Dystrophic EB Type) (ITT Population)  
Ad-hoc Figure 14.2.2.16 
Kaplan-Meier Curve for Target Wound Closure within 44 Days 
(Baseline BSAI of Total Body Wound Burden >=5%) (ITT Population)  
Ad-hoc Figure 14.2.2.17 
Complete Target Wound Closure over Time by Age Group 
(ITT Population)  
Ad-hoc Figure 14.2.2.18 
Complete Target Wound Closure over Time by Baseline BSAI of Total 
Body Wound Burden Group (ITT Population)  
Ad-hoc Figure 14.2.2.19 
Complete Target Wound Closure over Time (Age 2 Years to <12 Years 
and Baseline BSAI of Total Body Wound Burden >=5%) (ITT 
Population)  
Ad-hoc Figure 14.2.2.20 
Complete Target Wound Closure over Time (Age 2 Years to <12 Years 
and Recessive Dystrophic EB Type) (ITT Population)  
Ad-hoc Figure 14.2.2.21 
Complete Target Wound Closure over Time by EB Type 
(ITT Population)  
Ad-hoc Figure 14.2.2.22 
Complete Target Wound Closure over Time by Target Wound Age 
Group (ITT Population)  
Figure 14.2.6.1 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (ITT Population)  
Ad-hoc Figure 14.2.6.1.2 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Age 2 Years to <12 Years) (ITT Population)  
Ad-hoc Figure 14.2.6.1.3 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Baseline Target Wound Age >30 Days) (ITT 
Population)  
Ad-hoc Figure 14.2.6.1.4 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Recessive Dystrophic EB Type) (ITT Population)  
Ad-hoc Figure 14.2.6.1.5 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population)  
Ad-hoc Figure 14.2.6.1.6 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Age 2 Years to <12 Years and Recessive Dystrophic 
EB Type) (ITT Population)  
Ad-hoc Figure 14.2.6.1.7 
Mean Change from Baseline in BSAI of Lesional Skin over Time by 
Treatment Groups (Age 2 Years to <12 Years and Baseline BSAI of 
Total Body Wound Burden >=5%) (ITT Population)  
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Figure Number 
Figure Title 
Figure 14.2.6.2.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 3 (ITT Population) 
Figure 14.2.6.2.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 3 by Treatment Groups (ITT Population) 
Figure 14.2.6.2.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 3 by Age Group (ITT Population) 
Figure 14.2.7.1 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (ITT Population)  
Ad-hoc Figure 14.2.7.1.2 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Age 2 Years to <12 Years) 
(ITT Population)  
Ad-hoc Figure 14.2.7.1.3 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Baseline Target Wound Age 
>30 Days) (ITT Population)  
Ad-hoc Figure 14.2.7.1.4 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Recessive Dystrophic EB Type) 
(ITT Population)  
Ad-hoc Figure 14.2.7.1.5 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Baseline BSAI of Total Body Wound 
Burden >=5%) (ITT Population)  
Ad-hoc Figure 14.2.7.1.6 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (ITT Population)  
Ad-hoc Figure 14.2.7.1.7 
Mean Change from Baseline in BSAI of Total Body Wound Burden 
over Time by Treatment Groups (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5% ) (ITT Population)  
Figure 14.2.7.2.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 (ITT Population) 
Figure 14.2.7.2.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 by Treatment Groups (ITT 
Population) 
Figure 14.2.7.2.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 by Age Group (ITT Population) 
Ad-hoc Figure 14.2.7.2.4 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 (Age 2 Years to <12 Years) 
(ITT Population) 
Ad-hoc Figure 14.2.7.2.5 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 (Baseline Target Wound Age 
>30 Days) (ITT Population) 
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Figure Number 
Figure Title 
Ad-hoc Figure 14.2.7.2.6 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 (Recessive Dystrophic EB Type) 
(ITT Population) 
Ad-hoc Figure 14.2.7.2.7 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 3 (Baseline BSAI of Total Body 
Wound Burden >=5%) (ITT Population) 
Figure 14.2.8.1 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 (Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.8.1.2 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Age 2 Years to <12 Years (Including Missing as 
Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.8.1.3 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Baseline Target Wound Age >30 Days 
(Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.8.1.4 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Recessive Dystrophic EB Type (Including 
Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.8.1.5 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Baseline BSAI of Total Body Wound Burden 
>=5% (Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.8.1.6 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Age 2 Years to <12 Years and Recessive 
Dystrophic EB Type (Including Missing as Non-improvement) 
(ITT Population) 
Ad-hoc Figure 14.2.8.1.7 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 for Patients with Age 2 Years to <12 Years and Baseline BSAI of 
Total Body Wound Burden >=5% (Including Missing as 
Non-improvement) (ITT Population) 
Figure 14.2.8.2 
Logit of Predicted Probability of Improvement in Itching Assessed at 
Day 7 (Excluding Missing) (ITT Population) 
Figure 14.2.9.1 
Logit of Predicted Probability of Improvement in Pain Assessed at 
Day 7 (Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.9.1.2 
Logit of Predicted Probability of Improvement in Pain Assessed at 
Day 7 for Patients with Age 2 Years to <12 Years (Including Missing as 
Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.9.1.3 
Logit of Predicted Probability of Improvement in Pain Assessed at 
Day 7 for Patients with Baseline Target Wound Age >30 Days 
(Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.9.1.4 
Logit of Predicted Probability of Improvement in Pain Assessed at 
Day 7 for Patients with Recessive Dystrophic EB (Including Missing as 
Non-improvement) (ITT Population) 
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Figure Number 
Figure Title 
Ad-hoc Figure 14.2.9.1.5 
Logit of Predicted Probability of Improvement in Pain Assessed at Day 
7 for Patients with Baseline BSAI of Total Body Wound Burden 
>=5% (Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.9.1.6 
Logit of Predicted Probability of Improvement in Pain Assessed at Day 
7 for Patients with Age 2 Years to <12 Years and Recessive Dystrophic 
EB Type (Including Missing as Non-improvement) (ITT Population) 
Ad-hoc Figure 14.2.9.1.7 
Logit of Predicted Probability of Improvement in Pain Assessed at Day 
7 for Patients with Age 2 Years to <12 Years and Baseline BSAI of 
Total Body Wound Burden >=5% (Including Missing as 
Non-improvement) (ITT Population) 
Figure 14.2.9.2 
Logit of Predicted Probability of Improvement in Pain Assessed at 
Day 7 (Excluding Missing) (ITT Population) 
Figure 14.2.10.1.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Week 2 (ITT Population) 
Figure 14.2.10.1.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Week 2 by Treatment Groups 
(ITT Population) 
Figure 14.2.10.1.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Week 2 by Age Group (ITT Population) 
Figure 14.2.10.2.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 1 (ITT Population) 
Figure 14.2.10.2.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 1 by Treatment Groups 
(ITT Population) 
Figure 14.2.10.2.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 1 by Age Group (ITT Population) 
Figure 14.2.10.3.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 2 (ITT Population) 
Figure 14.2.10.3.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 2 by Treatment Groups 
(ITT Population) 
Figure 14.2.10.3.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Total Body Wound Burden at Month 2 by Age Group (ITT Population) 
Figure 14.2.11.1.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Week 2 (ITT Population) 
Figure 14.2.11.1.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Week 2 by Treatment Groups 
(ITT Population) 
Figure 14.2.11.1.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Week 2 by Age Group 
(ITT Population) 
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Figure Number 
Figure Title 
Figure 14.2.11.2.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 1 (ITT Population) 
Figure 14.2.11.2.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 1 by Treatment Groups 
(ITT Population) 
Figure 14.2.11.2.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 1 by Age Group 
(ITT Population) 
Figure 14.2.11.3.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 2 (ITT Population) 
Figure 14.2.11.3.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 2 by Treatment Groups 
(ITT Population) 
Figure 14.2.11.3.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 2 by Age Group 
(ITT Population) 
Figure 14.2.11.4.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 3 (ITT Population) 
Figure 14.2.11.4.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 3 by Treatment Groups 
(ITT Population) 
Figure 14.2.11.4.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Total Body Wound Burden at Month 3 by Age Group 
(ITT Population) 
Figure 14.2.12.1.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Week 2 (ITT Population) 
Figure 14.2.12.1.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Week 2 by Treatment Groups (ITT 
Population) 
Figure 14.2.12.1.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Week 2 by Age Group (ITT Population) 
Figure 14.2.12.2.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 1 (ITT Population) 
Figure 14.2.12.2.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 1 by Treatment Groups 
(ITT Population) 
Figure 14.2.12.2.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 1 by Age Group (ITT Population) 
Figure 14.2.12.3.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 2 (ITT Population) 
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Figure Number 
Figure Title 
Figure 14.2.12.3.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 2 by Treatment Groups 
(ITT Population) 
Figure 14.2.12.3.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 2 by Age Group (ITT Population) 
Figure 14.2.12.4.1 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 3 (ITT Population) 
Figure 14.2.12.4.2 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 3 by Treatment Groups 
(ITT Population) 
Figure 14.2.12.4.3 
Q-Q Plot for Testing Normality of Percent Change from Baseline in 
BSAI of Lesional Skin at Month 3 by Age Group (ITT Population) 
Figure 14.2.13.1.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Week 2 (ITT Population) 
Figure 14.2.13.1.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Week 2 by Treatment Groups (ITT Population) 
Figure 14.2.13.1.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Week 2 by Age Group (ITT Population) 
Figure 14.2.13.2.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 1 (ITT Population) 
Figure 14.2.13.2.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 1 by Treatment Groups (ITT Population) 
Figure 14.2.13.2.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 1 by Age Group (ITT Population) 
Figure 14.2.13.3.1 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 2 (ITT Population) 
Figure 14.2.13.3.2 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 2 by Treatment Groups (ITT Population) 
Figure 14.2.13.3.3 
Q-Q Plot for Testing Normality of Change from Baseline in BSAI of 
Lesional Skin at Month 2 by Age Group (ITT Population) 
Figure 14.2.15.1 
Improvement in Target Wound Characteristics over Time 
(ITT Population) 
Ad-hoc Figure 14.2.15.1.2 
Improvement in Target Wound Characteristics over Time (Age 2 Years 
to <12 Years) (ITT Population) 
Ad-hoc Figure 14.2.15.1.3 
Improvement in Target Wound Characteristics over Time (Baseline 
Target Wound Age >30 Days) (ITT Population) 
Ad-hoc Figure 14.2.15.1.4 
Improvement in Target Wound Characteristics over Time (Recessive 
Dystrophic EB Type) (ITT Population) 
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Figure Number 
Figure Title 
Ad-hoc Figure 14.2.15.1.5 
Improvement in Target Wound Characteristics over Time (Baseline 
BSAI of Total Body Wound Burden >=5%) (ITT Population) 
Ad-hoc Figure 14.2.15.1.6 
Improvement in Target Wound Characteristics over Time (Age 2 Years 
to <12 Years and Baseline BSAI of Total Body Wound Burden >=5%) 
(ITT Population) 
Ad-hoc Figure 14.2.15.1.7 
Improvement in Target Wound Characteristics over Time (Age 2 Years 
to <12 Years and Recessive Dystrophic EB Type) (ITT Population) 
Figure 14.2.16.1.1 
Improvement in Itching over Time (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.1.1.2 Improvement in Itching over Time (Age 2 Years to <12 Years) (Day 1 
to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.1.1.3 Improvement in Itching over Time (Baseline Target Wound Age 
>30 Days) (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.1.1.4 Improvement in Itching over Time (Recessive Dystrophic EB Type) 
(Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.1.1.5 Improvement in Itching over Time (Baseline BSAI of Total Body 
Wound Burden >=5%) (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.1.1.6 Improvement in Itching over Time (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (Day 1 to Day 7) 
Ad-hoc Figure 14.2.16.1.1.7 Improvement in Itching over Time (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Day 1 to Day 7) (ITT Population) 
Figure 14.2.16.1.2 
Improvement in Itching over Time (Week 2 to Month 3) 
(ITT Population) 
Ad-hoc Figure 14.2.16.1.2.2 Improvement in Itching over Time (Age 2 Years to <12 Years) (Week 2 
to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.1.2.3 Improvement in Itching over Time (Baseline Target Wound Age 
>30 Days) (Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.1.2.4 Improvement in Itching over Time (Recessive Dystrophic EB Type) 
(Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.1.2.5 Improvement in Itching over Time (Baseline BSAI of Total Body 
Wound Burden >=5%) (Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.1.2.6 Improvement in Itching over Time (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (Week 2 to 
Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.1.2.7 Improvement in Itching over Time (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Week 2 to Month 3) (ITT Population) 
Figure 14.2.16.2.1 
Improvement in Pain over Time (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.2.1.2 Improvement in Pain over Time (Age 2 Years to <12 Years) (Day 1 to 
Day 7) (ITT Population) 
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Figure Number 
Figure Title 
Ad-hoc Figure 14.2.16.2.1.3 Improvement in Pain over Time (Baseline Target Wound Age 
>30 Days) (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.2.1.4 Improvement in Pain over Time (Recessive Dystrophic EB Type) 
(Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.2.1.5 Improvement in Pain over Time (Baseline BSAI of Total Body Wound 
Burden >=5%) (Day 1 to Day 7) (ITT Population) 
Ad-hoc Figure 14.2.16.2.1.6 Improvement in Pain over Time (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (Day 1 to Day 7) 
Ad-hoc Figure 14.2.16.2.1.7 Improvement in Pain over Time (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Day 1 to Day 7) (ITT Population) 
Figure 14.2.16.2.2 
Improvement in Pain over Time (Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.2.2.2 Improvement in Pain over Time (Age 2 Years to <12 Years) (Week 2 to 
Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.2.2.3 Improvement in Pain over Time (Baseline Target Wound Age 
>30 Days) (Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.2.2.4 Improvement in Pain over Time (Recessive Dystrophic EB Type) 
(Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.2.2.5 Improvement in Pain over Time (Baseline BSAI of Total Body Wound 
Burden >=5%) (Week 2 to Month 3) (ITT Population) 
Ad-hoc Figure 14.2.16.2.2.6 Improvement in Pain over Time (Age 2 Years to <12 Years and 
Baseline BSAI of Total Body Wound Burden >=5%) (Week 2 to 
Month 3) 
Ad-hoc Figure 14.2.16.2.2.7 Improvement in Pain over Time (Age 2 Years to <12 Years and 
Recessive Dystrophic EB Type) (Week 2 to Month 3) (ITT Population) 
11.5 
List of Listings 
Listing Number 
Listing Title 
Listing 16.2.1 
Patients Disposition (All Patients) 
Listing 16.2.2 
Protocol Deviations (ITT Population) 
Listing 16.2.4.1 
Demographics and Baseline Data (ITT Population) 
Listing 16.2.4.2 
Medical History (Safety Population) 
Listing 16.2.6.1 
Body Surface Area Index of Lesional Skin by Visit (ITT Population) 
Listing 16.2.6.2 
Body Surface Area Index of Total Body Wound Burden by Visit 
(ITT Population) 
Listing 16.2.6.3 
Itch Man Pruritus Assessment Tool (ITT Population) 
Listing 16.2.6.4 
FLACC Pain Scale (ITT Population) 
Scioderm, Inc., An Amicus Therapeutics Company 
Clinical Study Report 
16.1 Study Information 
Study SD-005 
11 May 2018 
 
Page 85 of 86


Statistical Analysis Plan 
CONFIDENTIAL 
Version 6.0 – Amendment 1 
Protocol: SD-005 
22 March2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 85 of 85 
Listing Number 
Listing Title 
Listing 16.2.6.5 
Wong-Baker Faces Pain Scale (ITT Population) 
Listing 16.2.7.1 
Treatment-Emergent Adverse Events (Safety Population) 
Listing 16.2.7.2 
Non-Treatment Emergent Adverse Events (Safety Population) 
Listing 16.2.7.3 
All Serious Adverse Events (Safety Population) 
Listing 16.2.7.4 
All Treatment-Emergent Serious Adverse Events (Safety Population) 
Listing 16.2.7.5 
All Adverse Events Leading to Death (Safety Population) 
Listing 16.2.7.6 
All Adverse Events Leading to Discontinuation (Safety Population) 
Listing 16.2.8 
Pregnancy Test (All Female Patients of Childbearing Potential) 
Listing 16.2.9 
Vital Signs (Safety Population) 
Listing 16.2.10 
Target Wound Closure (ITT Population)  
Listing 16.2.11 
Prior and Concomitant Medications (Safety Population) 
Ad-hoc Listing 16.2.12 
Analysis Populations (ITT Population) 
Ad-hoc Listing 16.2.13 
Physical Examination (Safety Population) 
Ad-hoc Listing 16.2.14 
Exposure (Safety Population) 
Ad-hoc Listing 16.2.15 
Target Wound Characteristics Assessment (ITT Population) 
Ad-hoc Listing 16.2.16 
Target Wound Assessment of Scarring (ITT Population) 
 
Scioderm, Inc., An Amicus Therapeutics Company 
Clinical Study Report 
16.1 Study Information 
Study SD-005 
11 May 2018 
 
Page 86 of 86