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: NA | Intervention model: SINGLE_GROUP
Enrollment: 152
Healthy volunteers: no

Brief summary:
The study aimed to assess the long-term safety of topical use of Zorblisa (SD-101-6.0) in participants with Epidermolysis Bullosa (EB).

Detailed description:
This was an open label, multi-center extension study to assess the long-term safety of topically applied SD-101-6.0 in participants with simplex, recessive dystrophic, and junctional non-Herlitz EB. SD-101-6.0 was applied topically once a day to the entire body. The planned duration of treatment with SD-101-6.0 for Study SD-006 was up to 48 months, with a safety follow-up period of 30 days; however, the study was terminated early by the sponsor. The maximum study duration completed by at least 1 participant, treatment and safety follow-up, was 37 months.

Participants who successfully completed Study SD-005 had the option to rollover into Study SD-006. The screening/baseline visit (Visit 1) occurred at Visit 5 (approximately 90 days from baseline) of Study SD-005. The Body Surface Area (BSA) assessments of lesional skin and wound burden performed at Visit 5 (approximately 90 days from baseline) for Study SD-005 were utilized as the baseline assessments for Study SD-006. Participants returned for follow-up visits at Month 1 then every 3 months.

At each visit, assessments included BSA of lesional skin and wound burden. For target wounds that are not closed by the end of Study SD-005, the ARANZ picture and calculation of target wound area at the final visit for Study SD-005 was used as the baseline area size of the target wound for Study SD-006. These unhealed target wounds from Study SD-005 were assessed via ARANZ SilhouetteStar™ at each subsequent scheduled visit until the target wound was documented as closed. Closed wounds were assessed for scarring.

Arms:
arm 1: All participants (or their caregivers) applied SD-101-6.0 cream topically once a day to the entire body for a period of up to 36 months.

Interventions: intervention 1: SD-101-6.0 cream
Intervention descriptions: intervention 1: SD-101 is a white, crystalline powder that is formulated within an odorless, soft, white cream base. SD-101-6.0 cream contains allantoin, a diureide glyoxylic acid, at a concentration of 6% and other excipients.

Protocol document:
Prot_000.pdf: 
An Open Label Multi-Center Extension Study to Evaluate the Long-term Safety of 
ZorblisaTM (SD-101-6.0) in Patients with Epidermolysis Bullosa 
IND No: 107480 
Protocol No: SD-006 
Version No: 
  EudraCT No: 
3 
2014-005679-96 
Date of Protocol: 17 December 2014 
Amendment 1 Date: 2 December 2015 
Amendment 2 Date:  10 November 2016 
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. & affiliates 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. 
Amicus


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
Scioderm, Inc. 
10 November 2016  (Version 3) 
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2 
1.
PROTOCOL SYNOPSIS
PROTOCOL TITLE 
An Open Label Multi-Center Extension Study 
to Evaluate the Long-term Safety of ZorblisaTM 
(SD-101-6.0) in Patients with Epidermolysis 
Bullosa 
PROTOCOL No. 
SD-006 
VERSION No. 
3 
SPONSOR 
Scioderm, Inc. 
An Amicus Therapeutics Company 
4601 Creekstone Drive 
Suite 160 
Durham, NC  27703 
INVESTIGATIONAL PRODUCT 
ZORBLISA (SD-101-6.0) 
PHASE OF DEVELOPMENT 
Open Label Extension 
INDICATION AND RATIONALE 
The aim is to assess the long-term safety of 
topical use of ZORBLISA in patients with 
Epidermolysis Bullosa (EB). 
STUDY DESIGN 
This is an open label, multi-center extension study 
to assess the long-term safety of topically applied 
ZORBLISA in Patients with Simplex, Recessive 
Dystrophic, and Junctional non-Herlitz 
Epidermolysis Bullosa. 
ZORBLISA will be applied topically, once a day, 
to the entire body for a period of 1440 days. This 
study may be further extended by amendment 
until either SD-101 becomes commercially 
available or the clinical development of SD-101 in 
EB is discontinued.  
Patients who have successfully completed Study 
SD-005 (on study drug at Visit 5) will have the 
option to roll over into the SD-006 study. The 
baseline visit (Visit 1) will occur at Visit 5 for 
SD-005. The Body Surface Area (BSA) 
assessments of lesional skin and wound burden 
performed at the Visit 5 for SD-005 will be 
utilized as the baseline assessment for SD-006. 
Patients will return for follow-up visits at Months 
1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
Scioderm, Inc. 
10 November 2016  (Version 3) 
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3 
45, and48 after Visit 1.  At each visit, assessments 
will include BSAI of lesional skin and wound 
burden. For target wounds that are not closed by 
the end of Study SD-005, the ARANZ picture and 
calculation of target wound area at the final visit 
for Study SD-005 will used as the baseline area 
size of the target wound for SD-006.  These 
unhealed target wounds from SD-005 will be 
assessed via ARANZ at each subsequent 
scheduled visit until the target wound is 
documented as closed. Closed wounds will be 
assessed for scarring. 
STUDY OBJECTIVES 
Primary Objective 
The primary objective is to demonstrate the long-
term safety of ZORBLISA in patients, with 
Simplex, Recessive Dystrophic, and Junctional 
non-Herlitz Epidermolysis Bullosa.   
Secondary Objectives 
The secondary objectives are to assess the 
efficacy of ZORBLISA in terms of the change in 
Body Surface Area (BSA) of lesional skin and 
wound burden; as well as closure of unhealed 
target wounds from the SD-005 study. 
PLANNED SAMPLE SIZE 
Up to approximately 150 patients are expected to 
roll over from Study SD-005 into this open-label 
extension. 
PATIENT POPULATION 
Inclusion Criteria 
1.
Informed Consent form signed by the subject
or subject's legal representative; if the subject
is under the age of 18 but capable of
providing assent, signed assent from the
subject.
2.
Subject (or caretaker) must be willing to
comply with all protocol requirements.
3.
Patients who completed the SD-005 study (on
study drug at Visit 5).


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
Scioderm, Inc. 
10 November 2016  (Version 3) 
 Page 4 of 31 
4 
PATIENT POPULATION 
Exclusion Criteria 
1.
Patients who do not meet the entry criteria
outlined above.
2.
Pregnancy or breastfeeding during the study.
(A urine pregnancy test will be performed at
the final visit for SD-005 for female patients
of childbearing potential and repeated at Visit
1 if these visits do not occur on the same day)
3.
Females of childbearing potential who are not
abstinent or not practicing a medically
acceptable method of contraception.
FORMULATION/DOSE 
ZORBLISA (containing 6% allantoin) 
ROUTE OF ADMINISTRATION 
Topical  
DURATION/FREQUENCY OF 
TREATMENT 
Once daily for 1440 days (48 months). 
SAFETY ASSESSMENTS 
The safety of ZORBLISA will be assessed by 
monitoring tolerability at the application sites, 
adverse events, and periodic physical 
examinations. 
STATISTICAL CONSIDERATIONS 
In general, results will be summarized using 
descriptive statistics.  Additional evaluations may 
be made to compare responses of patients in this 
extension study with their responses in SD-005. 


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
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10 November 2016 (Version 3) 
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2.
TABLE OF CONTENTS
PAGE 
1.
PROTOCOL SYNOPSIS ......................................................................................................... 2 
2.
TABLE OF CONTENTS   PAGE ............................................................................................ 5 
3.
LIST OF ABBREVIATIONS .................................................................................................. 7 
4.
ADMINISTRATIVE STRUCTURE ........................................................................................ 8 
5.
BACKGROUND INFORMATION ......................................................................................... 9 
5.1. 
Overview of Active Ingredient and Drug Product Formulation (SD-101) .................. 9 
5.1.1. 
Pharmacology of Allantoin ......................................................................... 9 
5.1.2. 
Pharmacokinetics of Allantoin ................................................................... 9 
5.1.3. 
SD-101 Topical Cream ............................................................................... 9 
5.2. 
Summary of Animal and Human Studies with SD-101 ............................................. 10 
6.
RATIONALE FOR STUDY .................................................................................................. 11 
7.
STUDY OBJECTIVES AND PURPOSE .............................................................................. 11 
7.1. 
Primary Objective ...................................................................................................... 11 
7.2. 
Secondary Objective .................................................................................................. 11 
8.
SELECTION AND WITHDRAWAL OF PATIENTS .......................................................... 11 
8.1. 
Subject Numbers ....................................................................................................... 11 
8.2. 
Inclusion Criteria ....................................................................................................... 11 
8.3. 
Exclusion Criteria ...................................................................................................... 12 
8.4. 
Withdrawal Criteria/Study Discontinuation .............................................................. 12 
8.5. 
Handling of Withdrawals........................................................................................... 12 
9.
STUDY DESIGN AND ENDPOINTS .................................................................................. 13 
9.1. 
Study Design ............................................................................................................. 13 
9.2. 
Primary Endpoint ....................................................................................................... 13 
9.3. 
Secondary Endpoints ................................................................................................. 13 
9.3.1. 
Change from Baseline of Body Surface Area of Lesional Skin ............... 13 
9.3.1.1. 
Definition of Lesional Skin for Assessment and 
Calculation of BSA Coverage ............................................... 13 
9.3.2. 
Change in Total Body Wound Burden Compared to Baseline ................. 14 
9.3.2.1. 
Definition of Wound for Assessment and 
Calculation of BSA Coverage ............................................... 15 
9.3.3. 
Assessment of Closure of Target Wounds Non-Healed from 
Study SD-005 ........................................................................................... 15 
9.3.3.1. 
ARANZ SilhouetteStar™ ..................................................... 16 
10. STUDY MEDICATION AND ADMINISTRATION ........................................................... 16 
10.1. 
Study Medication and Administration ....................................................................... 16 
10.2. 
Selection of doses in the study .................................................................................. 16 
10.3. 
Allocation to Treatment ............................................................................................. 17 
10.4. 
Duration of Patient Participation ............................................................................... 17 
10.5. 
Treatment Accountability and Compliance Checks .................................................. 17 
10.6. 
Concurrent Therapy ................................................................................................... 17 
11. STUDY SCHEDULE ............................................................................................................. 18 


Investigational product: 
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Protocol No.: SD-006 
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10 November 2016 (Version 3) 
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12. EFFICACY ASSESSMENTS ................................................................................................ 20 
13. SAFETY ASSESSMENTS .................................................................................................... 20 
13.1. 
Physical Examination including Height, Weight, and Temperature ......................... 20 
13.2. 
Urinalysis ................................................................................................................... 20 
13.3. 
Adverse Events .......................................................................................................... 20 
13.3.1 Definitions ................................................................................................................. 21 
13.3.2 
Assessment of Causality ........................................................................... 22 
13.3.3 
Adverse Event Reporting .......................................................................... 23 
13.4. 
Concomitant Medications .......................................................................................... 23 
14. STATISTICAL CONSIDERATIONS ................................................................................... 23 
14.1. 
Sample Size ............................................................................................................... 23 
14.2. 
Study Populations ...................................................................................................... 23 
14.3. 
Analysis Considerations ............................................................................................ 23 
15. END OF THE STUDY ........................................................................................................... 24 
16. ETHICAL CONDUCT OF THE STUDY .............................................................................. 24 
16.1. 
Independent Ethics Committee (IEC) and Relevant Authorities ............................... 24 
16.2. 
Informed Consent ...................................................................................................... 25 
17. STUDY AND DATA MANAGEMENT ............................................................................... 25 
17.1. 
Protocol Amendments ............................................................................................... 25 
17.2. 
Monitoring ................................................................................................................. 25 
17.3. 
Quality Assurance ..................................................................................................... 26 
17.4. 
Data Recording .......................................................................................................... 26 
17.5. 
Data to be Considered as Source Data ....................................................................... 26 
17.6. 
Confidentiality ........................................................................................................... 26 
17.7. 
Retention of Study Data ............................................................................................ 27 
17.8. 
Communication and Publication of Results .............................................................. 27 
18. SIGNATURES AND AGREEMENT WITH THE PROTOCOL .......................................... 28 
19. APPENDICES ........................................................................................................................ 30
19.1. 
Appendix 1 Epidermolysis Bullosa Subtypes............................................................ 30 


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
Scioderm, Inc. 
10 November 2016 (Version 3) 
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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 
EB 
Epidermolysis Bullosa 
EBS 
Epidermolysis Bullosa Simplex 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
JEB-nH 
Junctional non-Herlitz EB 
PP 
Per Protocol 
RDEB 
Recessive Dystrophic Epidermolysis Bullosa 
SAE 
Serious Adverse Event 
SD-101 
Drug Product Formulation 
SD-101-0.0 
Contains 0% allantoin (placebo) 
SD-101-1.5 
Contains 1.5% allantoin 
SD-101-3.0 
Contains 3% allantoin  
SD-101-6.0 
Contains 6% allantoin – referred to as ZORBLISA 
SD-101-9.0 
Contains 9% allantoin 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
WMA 
World Medical Association 


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
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10 November 2016 (Version 3) 
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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 
Amicus
Amicus


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0) 
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10 November 2016 (Version 3) 
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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 (see Appendix 1 Epidermolysis Bullosa Subtypes). 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 Formulation (SD-101) 
5.1.1. 
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. 
5.1.2. 
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. 
5.1.3. 
SD-101 Topical Cream 
Allantoin is the active ingredient contained within the SD-101 topical product, 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 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
 Page 10 of 31  
 
with SD-101 containing allantoin ranging from 0.5 to 9%, penetration across the various skin 
barriers was dose-related. 
The SD-101 proprietary formulation 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%. 
The SD-101 topical product 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 (containing various 
concentrations of allantoin) 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, SD-101-3.0, and 
SD-101-6.0) demonstrated 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 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 placebo 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 


Investigational product: 
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Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
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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. The results of Study SD-003 support 
that SD-101-6.0 is the most efficacious and safe concentration. It is the concentration used in the 
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 are the population for this 
study. 
6. 
RATIONALE FOR STUDY 
The aim is to assess the long-term safety of ZORBLISA in the treatment of patients with 
Epidermolysis Bullosa. 
7. 
STUDY OBJECTIVES AND PURPOSE 
7.1. 
Primary Objective 
The primary objective is to demonstrate the long-term safety of ZORBLISA in patients with 
Simplex, Recessive Dystrophic, and Junctional non-Herlitz Epidermolysis Bullosa. 
7.2. 
Secondary Objective 
The secondary objectives are to assess the efficacy of ZORBLISA in terms of the change in Body 
Surface Area (BSA) of lesional skin and wound burden; as well as assessment of closure of 
unhealed target wounds in patients rolling over from the SD-005 study. 
8. 
SELECTION AND WITHDRAWAL OF PATIENTS 
8.1. 
Subject Numbers 
Approximately 150 EB patients will be enrolled at study sites worldwide, following completion 
of their participation in Study SD-005. 
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 subject or subject's legal representative; if the 
subject is under the age of 18 but capable of providing assent, signed assent from the 
subject. 
2. Subject (or caretaker) must be willing to comply with all protocol requirements. 
3. Patients who completed the SD-005 study (on study drug at Visit 5). 
 


Investigational product: 
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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.
Pregnancy or breastfeeding during the study. (A urine pregnancy test will be performed
at the final visit for SD-005 for female patients of childbearing potential and repeated
at Visit 1 if these visits do not occur on the same day)
3.
Females of childbearing potential who are not abstinent or not practicing a medically
acceptable method of contraception.
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 subject from the study and discontinue 
study treatment and assessments at any time due to safety concerns.  Full skin examination will 
be performed at each visit.  If ZORBLISA causes any significant rash that has not occurred 
previously in the subject, the Investigator should consider discontinuing the subject.  In addition, 
if lesions appear to significantly worsen above the normal cycle seen in the patient, with use of 
ZORBLISA, the investigator should consider discontinuing the subject.    
Early discontinuation of any subject who has given informed consent /assent to participate will be 
recorded including the reason for discontinuation. The primary reason for a subject withdrawing 
prematurely will be selected from the following standard categories of early discontinuations. 
1.
Adverse Event and Adverse Reactions: Clinical events occurred that are reported that in the
medical judgment of the investigator are grounds for discontinuation in the best interests of
the subject.
2.
Withdrawal of Consent: The subject desired to withdraw from further participation in the
study. The subject 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 subject failed to adhere to the protocol requirements, at the
investigator’s discretion.
4.
Lost to Follow-Up: The subject stopped coming for visits and study personnel were
unable to contact the subject.
5. Other: The subject was terminated for a reason other than those listed above, such as,
termination of study by Sponsor.
8.5. 
Handling of Withdrawals 
Although a subject 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 
subject’s rights.  In the case of withdrawal due to an adverse event the subject will be followed 
per Section 13.3.  Reasonable efforts will be made to contact a subject who fails to attend any 
follow-up appointments, to ensure that he/she is in satisfactory health.   


Investigational product: 
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Protocol No.: SD-006 
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9. 
STUDY DESIGN AND ENDPOINTS 
9.1. 
Study Design 
This is an open label, multi-center extension study to assess the long-term safety of ZORBLISA 
in treating patients with Simplex, Recessive Dystrophic, and Junctional non-Herlitz 
Epidermolysis Bullosa.  All patients must have completed SD-005 to be eligible to participate in 
this open label extension.   
 
ZORBLISA will be applied topically, once a day, to the entire body for a period of 1440 days. 
Patients will return to the study site at Month 1, then once every 3 months until Month 48 
(Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48). 
 
9.2. 
Primary Endpoint 
The primary endpoint is the long-term safety of ZORBLISA in patients with Simplex, Recessive 
Dystrophic, and Junctional non-Herlitz Epidermolysis Bullosa. Safety is assessed via monitoring 
of local tolerability at the application sites, occurrence of adverse events and physical 
examinations. 
9.3. 
Secondary Endpoints 
The secondary endpoints include the change from baseline in BSA coverage of lesional skin and 
wound burden; as well as closure of unhealed target wounds from the SD-005 study. 
9.3.1. 
Change from Baseline of Body Surface Area of Lesional Skin 
Change in lesional skin based on BSA estimates at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 
33, 36, 39, 42, 45, and 48 compared to Baseline will be measured using the Body Surface Area 
Index (BSAI). The BSAI is a global measure of disease extent 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. The BSA will be assessed as in Figure 9-1 per 
the definition below by a study physician. Preferably the same study physician will perform this 
assessment at each patient visit. 
9.3.1.1. 
Definition of Lesional Skin for Assessment and Calculation of BSA Coverage 
• 
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.   
- 
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 do 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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Figure 9-1:  BSAI of Lesional Skin Calculation Charts 
(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. 
 
9.3.2. 
Change in Total Body Wound Burden Compared to Baseline 
Change in total body wound coverage based on BSA estimates at Months 1, 3, 6, 9, 12, 15, 18, 
21, 24, 27, 30, 33, 36, 39, 42, 45, and 48 compared to Baseline will be measured using the BSAI.  
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 to assess the total wound area before and 
after using the product. The BSA of wounds will be assessed by a study physician as per Figure 
9-2. Preferably the same study physician will perform this assessment for each patient visit.  


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9.3.2.1. 
Definition of Wound for Assessment and Calculation of BSA Coverage 
A wound is defined as an open area on the skin (epidermal covering is disrupted). 
Figure 9-2:  BSAI of Total Wound Burden Calculation Charts 
(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. 
 
9.3.3. 
Assessment of Closure of Target Wounds Non-Healed from Study SD-005 
For target wounds that are not closed by the end of Study SD-005, the ARANZ picture and 
calculation of target wound area at the final visit for Study SD-005 will be used as the baseline 
area size of the target wound for SD-006.  The unhealed target wound from SD-005 will be 


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10 November 2016 (Version 3) 
 
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assessed via the ARANZ SilhouetteStar™ at each subsequent scheduled visit until the target 
wound is documented as closed. The closed target wound will be assessed for scarring. 
9.3.3.1. 
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.   
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 9-3 
ARANZ SilhouetteStar™ 
10. 
STUDY MEDICATION AND ADMINISTRATION 
10.1. 
Study Medication and Administration 
ZORBLISA will be supplied in 8-ounce tubes, to be reclosed after use and stored at room 
temperature. 
ZORBLISA will be applied once a day to the entire body for a period of 1440 days (48 months).  
The study cream will be returned at Visit 3, and all visits up to and including Visit 18 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 
All patients will receive ZORBLISA (containing 6% allantoin) daily.  


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10.3. 
Allocation to Treatment 
All patients will receive open-label ZORBLISA. 
10.4. 
Duration of Patient Participation 
It is anticipated that each eligible subject will participate in the trial for approximately 1440 days.  
This study may be further extended by amendment until either SD-101 becomes commercially 
available or the clinical development of SD-101 in EB is discontinued. 
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 will be destroyed in accordance with CRO processes 
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 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. 
Concurrent Therapy 
Medications considered necessary for the subject’s welfare may be given at the discretion of the 
investigator.  The administration of all such medication / therapy must be recorded in the 
appropriate section of the eCRF.   
 


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11. 
STUDY SCHEDULE 
 
Procedure 
Visit 
 
1 
Screening/Baseline 
 
2 
Month 
1 
 
3 
Month 
3 
 
4 
Month 
6 
 
5 
Month 
9 
 
6 
Month 
12  
7 to 17 
Month  
15 to 45a 
 
(Every 3 months) 
 
18 
Month 48 
Final Visit/ 
Early 
Termination 
 
Study Day  
(± 7 Days for Visits 2 – 18) 
0 
30 
90 
180 
270 
360 
450 to 1350  
1440 
Informed consent /assent signed 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion assessment  
X 
 
 
 
 
 
 
 
Demographic, medical and medication historyb 
X 
 
 
 
 
 
 
 
Physical examinationc 
X 
 
 
 
 
 
 
X 
Height, weight, and temperaturec 
X 
 
 
 
 
 
 
X 
Assess BSA of lesional skind 
X 
X 
X 
X 
X 
X 
X 
X 
Assess BSA of wound burdend 
X 
X 
X 
X 
X 
X 
X 
X 
Assess target wound via ARANZe 
X 
X 
X 
X 
X 
X 
X 
X 
Bandage history 
X 
 
X 
X 
X 
X 
X 
X 
Urine pregnancy test (females of child-bearing 
potential only)f 
X 
 
X 
X 
X 
X 
X 
X 
Dispense ZORBLISAg 
X 
 
X 
X 
X 
X 
X 
 
Collect ZORBLISA for the purpose of drug 
accountability 
 
 
X 
X 
X 
X 
X 
X 
Collect all ZORBLISA 
 
 
 
 
 
 
 
X 
Monitor adverse eventsh 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor use of concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 


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a. 
Patients will return once every 3 months for Visit 7 (Month 15; day 450), Visit 8 (Month 18; day 540), Visit 9 (Month 21; day 630), Visit 10 (Month 24; 
day 720), Visit 11 (Month 27; day 810), Visit 12 (Month 30; day 900), Visit 13 (Month 33; day 990), Visit 14 (Month 36; day 1080), Visit 15 (Month 39; day 
1170), Visit 16 (Month 42; day 1260), and Visit 17 (Month 45; day 1350). 
b. Demographic, medical and medication history collected during SD-005 will be utilized as the baseline information for SD-006 
c. 
The physical examination, as well as, height, weight, and temperature performed at the final visit for SD-005 will be utilized as the baseline assessment for 
SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case the assessment will be repeated. A complete physical examination, as well as, 
height, weight, and temperature will be performed at visit 18.   
d. The BSA assessments of lesional skin and wound burden performed at the final visit for SD-005 will be utilized as the baseline assessment for SD-006 unless 
Visit 1 is ≥ 14 days after the final SD-005 visit in which case the assessment will be repeated. The BSA assessments of lesional skin and wound burden will be 
performed at visits 2 through 18.   
e. 
If the target wound has not healed by the final visit of the SD-005 study, the target wound will be assessed in SD-006 using ARANZ until the wound has healed. 
The ARANZ picture and target wound area value determined at the final visit for SD-005 will be utilized as the baseline target wound area and picture for 
SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case the assessment will be repeated. If target wound has healed, assess for scarring. 
f. 
The urine pregnancy test performed at the final visit for SD-005 will be utilized for entry into SD-006 if the visits occur on the same day. Otherwise, the urine 
pregnancy test will be performed at Visit 1 and at Visits 3 through 18. 
g. Ensure the patient is dispensed sufficient ZORBLISA until the next study visit. 
h. All AEs experienced in SD-005 should be noted in medical history for SD-006 at Visit 1 only. 
 
 


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12.
EFFICACY ASSESSMENTS
The body surface coverage (BSA) of lesional skin and wound burden will be measured at each 
visit via the BSAI as described in Sections 9.3.1 and 9.3.2 to monitor the extent of coverage 
with extended use of ZORBLISA. 
Any target wound not completely healed during the SD-005 study will continue to be 
monitored for closure at each study visit, as described in Section 9.3.3. 
13.
SAFETY ASSESSMENTS
The safety of ZORBLISA applied to the skin will be assessed by monitoring tolerability at the 
application sites, adverse events, and physical examinations. 
For timing of individual measurements, refer to Section 11 - Study Schedule. 
13.1. 
Physical Examination including Height, Weight, and Temperature 
The physical examination performed at the final visit for SD-005 will be utilized as the baseline 
assessment for SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case a 
physical examination will be repeated An additional physical examination will be done by a 
physician at Visit 18.  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, and temperature will be recorded. 
13.2. 
Urinalysis 
The urine pregnancy test performed at the final visit for SD-005 will be utilized for entry (Visit 1) 
into SD-006 only if the visits occur on the same day, otherwise, urine pregnancy test will be 
performed at Visit 1. Urine pregnancy tests for female patients of child bearing potential 
(sensitivity at least 25 mIU/ml) will also be performed at Visit 3 through 18.   
13.3. 
Adverse Events 
Adverse events may be volunteered spontaneously by the patient or discovered as a result of 
general, non-leading questioning.  All adverse events should be recorded in the Case Report 
Form.  Adverse events will be collected after signing the informed consent/assent through Visit 
18. Information on AEs will be followed to 30 days after the last dose of study drug has been
administered. 
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. 
Note: All AEs experienced in SD-005 and medical events occurring between the end of SD-005 
and the enrollment into SD-006 after completion of SD-005 should be noted in the medical 
history for SD-006 at Visit 1 only. 


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13.3.1 
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 adverse event (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. 
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, with the exception of skin site changes 
captured during the skin site evaluations (refer to Section 9.3).  A lack of efficacy (i.e. 
worsening EB) should not be considered an ADR. Changes outside of the intended effect (e.g. 
rash) should be considered ADRs.  The phrase “responses to a medicinal product” means that a 
causal relationship between a medicinal product and an adverse event is at least a reasonable 
possibility, i.e., the relationship cannot be ruled out. 
Serious Adverse Event (SAE) 
An adverse event that: 
•
Results in death
•
Is life-threatening (i.e. 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 a serious adverse event. 
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 adverse event is not an SAE. 


Investigational product: 
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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 AE or SAE. 
Unexpected Adverse Drug Reaction 
An adverse reaction, the nature or severity of which is not consistent with applicable product 
information (e.g., Investigators Brochure). 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A SUSAR is a serious adverse event 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. 
13.3.2 
Assessment of Causality 
Severity 
The severity (intensity) of each adverse event 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 adverse event 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. 


Investigational product: 
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10 November 2016 (Version 3) 
 
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- 
Event cannot be explained by patient’s clinical state or other factors. 
 
13.3.3 
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 IRBs, where required, and to the regulatory authorities of all adverse drug reactions (ADRs) 
that are serious unexpected and reasonably associated 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 will submit to the regulatory authorities all safety updates and periodic reports, as 
required by applicable regulatory requirements. 
13.4. 
Concomitant Medications 
All concomitant medications will be recorded.  In addition, concomitant medications will be 
coded for those patients that experience adverse events. 
14. 
STATISTICAL CONSIDERATIONS 
14.1. 
Sample Size 
All patients who complete the basic protocol SD-005 (on study drug at Visit 5) and who wish to 
receive ZORBLISA will be eligible to enter this open label extension. 
14.2. 
Study Populations 
Study populations are the same as defined for SD-005. 
14.3. 
Analysis Considerations 
In general, results will be summarized using descriptive statistics.  Summary statistics to be used 
include proportion of patients with complete closure of their target lesion at each visit, mean and 
standard deviation of BSAI compared with baseline at each visit, and incidence rates of specific 
adverse events. 
Additional evaluations may be made to compare responses of patients in this extension study with 
their responses in SD-005.  For those patients randomized to ZORBLISA in SD-005, the use of 
summary statistics as described in the previous paragraph will provide an understanding of the 
long term effect of ZORBLISA in these patients.  For those patients randomized to the control 
arm in SD-005, summary statistics will be used to compare their response to ZORBLISA in 
SD-006 with their response to control in SD-005. 
In addition to the evaluations described above for the primary efficacy and safety variables, 
secondary and exploratory variables will also be evaluated using summary statistics. 


Investigational product: 
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15. 
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/ECs, 
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 adverse events 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. 
7. If SD-101 becomes commercially available, 
the Sponsor may transition subjects to commercial drug supply. 
 
16. 
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). 
16.1. 
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. 


Investigational product: 
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16.2. 
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. 
17. 
STUDY AND DATA MANAGEMENT 
17.1. 
Protocol Amendments 
No amendments to the protocol will be implemented prior to agreement from the Sponsor, and 
prior to approval from appropriate authorities. 
17.2. 
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, 
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 communications between the Sponsor, designated study representative, and Investigator 
should be documented for the study file. 


Investigational product: 
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17.3. 
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. 
17.4. 
Data Recording 
The investigator has the responsibility for ensuring that all source documents (i.e., study and/or 
medical records) are completed and maintained according to the study protocol, and are available 
at the site. 
17.5. 
Data to be Considered as Source Data 
The following are considered source data: Informed consents, laboratory reports, patient files, and 
IMP accountability list. 
The following information must be entered in the patient’s file: 
- 
Patient’s name, address and date of birth 
- 
Patient’s weight, height, 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 patient  
- 
Date of informed consent / assent 
- 
Physical examinations and results done at the appropriate visits  
- 
Dates and time of urine pregnancy test 
- 
Anatomical location of the target wound and corresponding ARANZ report with 
photograph 
- 
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 subject i.e., telephone, email, certified letter 
 
All other data recorded directly in the eCRF [i.e., no prior written or electronic record of data] 
will be considered as source data. 
17.6. 
Confidentiality 
The Investigator must assure that the patients’ anonymity will be maintained.  On all study 
documentation, with the exception of the consent form and patient ID logs, patients will only be 
identified by their unique identification code and initials and will not be referred to by name. 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
 Page 27 of 31  
 
17.7. 
Retention of Study Data 
The Investigator is required to maintain all study documentation, including regulatory documents, 
copies of eCRFs, signed informed consent forms, and records for the receipt and disposition of 
study medications, for a period of two years following approval date of a New Drug Application 
for the drug, or until 15 years after completion of the study, whichever is later. 
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 informed consent/assent form 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. 
17.8. 
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.  
• 
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). 


10 Nov 2016
Amicus
Amicus
Amicus


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
 Page 29 of 31  
 
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: 
                                         
 
 
Principal Investigator 
 
 
 
 
 
Printed:            ________________________ 
 
 
Name of Principal Investigator 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
 Page 30 of 31  
 
19. 
APPENDICES 
19.1. 
Appendix 1 
Epidermolysis Bullosa 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.  
 
 
 
 
 


Investigational product: 
CONFIDENTIAL 
Protocol No.: SD-006 
Zorblisa™ (SD-101-6.0)  
 
Scioderm, Inc. 
 
 
10 November 2016 (Version 3) 
 
 Page 31 of 31  
 
 
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.  
 

SAP_001.pdf: 
Protocol SD-006 
An Open Label Multi-Center Extension Study to Evaluate the Long-term Safety of 
ZORBLISATM (SD-101-6.0) in Patients with Epidermolysis Bullosa 
Statistical Analysis Plan 
Final Version 2.0 
Date 22 August 2018 
CONFIDENTIAL 
Sponsor: 
Scioderm, Inc. 
An Amicus Therapeutics Company 
4601 Creekstone Drive 
Suite 160 
Durham, NC 27703 
The information in this document is the property of Amicus Therapeutics, Inc. and is 
strictly confidential. Neither the document nor the information contained herein may be 
reproduced or disclosed outside of Amicus Therapeutics, Inc. without the prior consent of 
the company. 


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 2 of 26 
REVISION HISTORY 
Version 
Date 
Revision Author 
Comments 
Draft 1.0 
20Dec2016 
Initial Version based on Protocol 
Version 3.1, 10Nov2016 
Draft 0.3 
28Jun2017 
Updates based on protocol 
amendment 2 and standard safety 
text 
Draft 0.4 
14Jul2017 
Updates of safety section for 
consistency with pivotal study 
SD-005 
Final 1.0 
31Jul2017 
Removal of time to wound 
healing analysis. Updates to 
safety section for consistency 
with SD-004. 
Final 2.0 
22Aug2018 
Subgroup analysis deleted from 
efficacy analyses.  Safety analysis 
limited to age subgroups. 
Amicus


Amicus
Amicus
Amicus
08
22
2018


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 4 of 26 
TABLE OF CONTENTS 
REVISION HISTORY.....................................................................................................................2 
SIGNATURE PAGE .......................................................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
1.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS...............................7 
2.
INTRODUCTION ........................................................................................................8 
3.
STUDY OBJECTIVE ...................................................................................................8 
4.
STUDY DESIGN .........................................................................................................8 
4.1. 
General Design .............................................................................................................8 
4.2. 
Method of Assignment of Patients to Treatment Groups .............................................8 
4.3. 
Blinding ........................................................................................................................8 
4.4. 
Determination of Sample Size ......................................................................................9 
5.
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED
ANALYSIS...................................................................................................................9 
5.1. 
Changes in the Conduct of the Study ...........................................................................9 
5.2. 
Changes from the Analyses Planned in the Protocol/CIP ............................................9 
6.
BASELINE, EFFICACY, AND SAFETY EVALUATIONS ......................................9 
6.1. 
Schedule of Evaluations ...............................................................................................9 
6.2. 
Time Point Algorithms ...............................................................................................12 
6.2.1. 
Study Day ...................................................................................................................12 
6.2.2. 
Windows .....................................................................................................................12 
6.3. 
Baseline Definition and Assessments .........................................................................13 
6.3.1. 
Baseline definition ......................................................................................................13 
6.3.2. 
Baseline assessments ..................................................................................................14 
6.4. 
Efficacy Assessments .................................................................................................15 
6.4.1. 
Change in Body Surface Area Index (BSAI) .............................................................15 
6.5. 
Safety Assessments .....................................................................................................15 
6.5.1. 
Extent of Exposure and Compliance to Study Treatment ..........................................15 
6.5.2. 
Adverse Events ...........................................................................................................15 
6.5.3. 
Clinical Laboratory Evaluations .................................................................................16 
6.5.4. 
Physical Examination including Height/Length, Weight and Temperature ...............16 
7.
STATISTICAL METHODS .......................................................................................17 
7.1. 
General Methodology .................................................................................................17 


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 5 of 26 
7.2. 
Adjustments for Covariates ........................................................................................17 
7.3. 
Handling of Dropouts or Missing Data ......................................................................17 
7.4. 
Multi-center Studies and Pooling of Centers ..............................................................17 
7.5. 
Multiple Comparisons/Multiplicity ............................................................................17 
7.6. 
Examination of Subgroups .........................................................................................17 
8.
STATISTICAL ANALYSIS ......................................................................................18 
8.1. 
Disposition of Patients ................................................................................................18 
8.2. 
Protocol Deviations ....................................................................................................18 
8.3. 
Analysis Populations ..................................................................................................18 
8.3.1. 
Intent-to-Treat (ITT) Population .................................................................................18 
8.3.2. 
Safety Population ........................................................................................................18 
8.4. 
Demographic and Other Baseline Characteristics ......................................................18 
8.5. 
Prior and Concomitant Therapy ..................................................................................19 
8.6. 
Analysis of Efficacy Parameters .................................................................................20 
8.6.1. 
Analysis of BSAI ........................................................................................................20 
8.7. 
Analysis of Safety .......................................................................................................20 
8.7.1. 
Extent of Exposure .....................................................................................................20 
8.7.2. 
Adverse Events by Preferred Term and System Organ Class ....................................20 
8.7.3. 
Summaries of Adverse Event Incidence Rates for All Patients .................................21 
8.7.4. 
Missing AE Onset, Severity, and Relationship ..........................................................21 
8.7.4.1. 
Missing or Partial AE Dates .......................................................................................21 
8.7.4.2. 
Missing Severity .........................................................................................................22 
8.7.4.3. 
Missing Relationship ..................................................................................................22 
8.7.5. 
Summaries of Adverse Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death ..........................................................................22 
8.7.6. 
Discontinuation from the Study ..................................................................................23 
8.7.7. 
Clinical Laboratory Evaluations .................................................................................23 
8.7.8. 
Other Observations Related to Safety .........................................................................23 
8.7.8.1. 
Vital Signs ..................................................................................................................23 
8.7.8.2. 
Physical Findings ........................................................................................................23 
9.
COMPUTER SOFTWARE ........................................................................................23 
10.
REFERENCES ...........................................................................................................24 
11.
APPENDICES ............................................................................................................25 


Statistical Analysis Plan 
 
Final Version 2.0 
Protocol: SD-006 
 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
 
Page 6 of 26 
11.1. 
Body Surface Area Index (BSAI) of Lesional Skin ...................................................25 
11.2. 
Body Surface Area Index (BSAI) of Total Wound Burden .......................................26 
 


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 7 of 26 
1.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
AE 
Adverse Event 
BSA 
Body Surface Area 
BSAI 
Body Surface Area Index 
CRF 
Case Report Form 
EB 
Epidermolysis bullosa 
EBS 
Epidermolysis bullosa Simplex 
EU 
European Union 
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
Placebo 
Contains 0% allantoin 
PP 
Per Protocol 
ROW 
Rest of the world, including all other countries except US and 
Europe  
SAE 
Serious Adverse Event 
SD-101 
Drug Product Formulation 
SD-101-6.0 
Contains 6% allantoin – referred to as Zorblisa in the study 
protocol  
Placebo –> SD-101-6.0 
Rolled over from 005 study placebo group 
SD-101-6.0 –> SD-101-6.0 Rolled over from 005 study SD-101-6.0 group 
SOC 
System Organ Class 
TEAE 
Treatment-emergent Adverse Event 
TESAE 
Treatment-emergent Serious Adverse Event 
US 
United States 


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 8 of 26 
2.
INTRODUCTION
This statistical analysis plan (SAP) defines the methodology and strategy for performing safety 
and efficacy analysis for patients with epidermolysis bullosa (EB). This SAP is based on the 
protocol amendment 2, version 2 dated 10 November 2016.
3.
STUDY OBJECTIVE
The primary objective is to demonstrate the long-term safety of SD-101-6.0 in patients with 
Simplex, Recessive Dystrophic, and Junctional non-Herlitz epidermolysis bullosa. 
The secondary objectives are to assess the efficacy of SD-101-6.0 in terms of the change in Body 
Surface Area Index (BSAI) of lesional skin and BSAI of wound burden; as well as assessment of 
healing of unhealed target wounds in patients rolling over from the SD-005 study.
4.
STUDY DESIGN
4.1. 
General Design 
This is an open label, multi-center extension study to assess the long-term safety of SD-101-6.0 
in treating patients with Simplex, Recessive Dystrophic, and Junctional non-Herlitz 
epidermolysis bullosa.  
SD-101-6.0 will be applied topically, once a day, to the entire body for a period of 1440 days 
(48 months). This study may be further extended by amendment until either SD-101 becomes 
commercially available or the clinical development of SD-101 in EB is discontinued.  
Patients who successfully completed Study SD-005 (on study drug at Visit 5) have had the 
option to roll over into the SD-006 study. The baseline visit (Visit 1) has occurred at Visit 5 for 
SD-005. The Body Surface Area Index (BSAI) assessments of lesional skin and wound burden 
performed at the final Visit for SD-005 are to be utilized as the baseline assessment for SD-006 
unless Visit 1 is ≥14 days after the final SD-005 visit in which case the assessment are to be 
repeated. Patients return for follow-up visits at Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 
36, 39, 42, 45, and 48 after Visit 1. At each visit, assessments include BSAI of lesional skin and 
wound burden. The unhealed target wounds from SD-005 are assessed at each subsequent 
scheduled visit until the target wound is documented as closed. Closed wounds will be assessed 
for scarring. 
4.2. 
Method of Assignment of Patients to Treatment Groups 
There will only be one treatment group so patients will not be randomized to treatment. All 
patients will receive SD-101-6.0.
4.3. 
Blinding 
This is an open-label study; therefore, blinding was not performed.


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 9 of 26 
4.4. 
Determination of Sample Size 
All patients who complete the study SD-005 (on study drug at Visit 5) and who meet all 
eligibility criteria may be eligible to enter this open label extension. Up to approximately 150 
patients are expected to roll over from Study SD-005.
5.
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED
ANALYSIS
5.1. 
Changes in the Conduct of the Study 
There were two amendments in the protocol. The first amendment was finalized on 2 December 
2015, the second amendment was finalized on 10 November 2016. The second amendment 
extends study period from 360 days to 1440 (48 months) days. On June 4, 2018, a Dear Doctor 
Letter was sent to all sites to discontinue the applications of SD-101 cream immediately, bring 
the patients back to the sites for the end of study visit and collect all the remaining tubes of SD-
101, because the manufacturer of SD-101 had received a warning letter from the FDA for several 
violations of GMP regulations that, although not mentioning SD-101, may have resulted in the 
adulteration of SD-101. 
5.2. 
Changes from the Analyses Planned in the Protocol/CIP 
Subgroup analysis deleted from efficacy analyses. Safety analysis limited to age subgroups. 
6.
BASELINE, EFFICACY, AND SAFETY EVALUATIONS
6.1. 
Schedule of Evaluations


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 10 of 26 
Table 1: 
Assessments Conducted at each Scheduled Visit 
Procedure 
Visit 
1 
Screening/ 
Baseline 
2 
Month 
1 
3 
Month 
3 
4 
Month 
6 
5 
Month 
9 
6 
Month 
12 
7 to 17 
Month 
15 to 45a
(Every 3 
months) 
18 
Month 48 
Final Visit/ 
Early 
Termination 
Study Day 
(± 7 Days for Visits 2 – 18) 
0 
30 
90 
180 
270 
360 
450 to 1350 
1440 
Informed consent /assent 
signed 
X 
Inclusion/Exclusion 
assessment 
X 
Demographic, medical and 
medication historyb
X 
Physical examinationc
X 
X 
Height, weight, and 
temperaturec
X 
X 
Assess BSA of lesional skind
X 
X 
X 
X 
X 
X 
X 
X 
Assess BSA of wound 
burdend
X 
X 
X 
X 
X 
X 
X 
X 
Assess target wound via 
ARANZe
X 
X 
X 
X 
X 
X 
X 
-
Bandage history 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test (females 
of child-bearing potential 
only) f
X 
X 
X 
X 
X 
X 
X 
Dispense SD-101-6.0g
X 
X 
X 
X 
X 
X 


Statistical Analysis Plan 
 
Final Version 2.0 
Protocol: SD-006 
 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
 
Page 11 of 26 
Table 1: 
Assessments Conducted at each Scheduled Visit (Continued) 
 
Procedure 
Visit 
 
1 
Screening/Bas
eline 
 
2 
Month 
1 
 
3 
Month 
3 
 
4 
Month 
6 
 
5 
Month 
9 
 
6 
Month 
12 
7 to 17 
Month 
15 to 45a 
(Every 3 
months) 
18 
Month 48 
Final Visit/ 
Early 
Termination 
Collect SD-101-6.0 for the 
purpose of drug accountability 
 
 
X 
X 
X 
X 
X 
X 
Collect all SD-101-6.0 
 
 
 
 
 
 
 
X 
Monitor adverse eventsh 
X 
X 
X 
X 
X 
X 
X 
X 
Monitor use of concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
a. 
Patients will return once every 3 months for Visit 7 (Month 15; day 450), Visit 8 (Month 18; day 540), Visit 9 (Month 21; day 630), Visit 10 (Month 24; day 
720), Visit 11 (Month 27; day 810), Visit 12 (Month 30; day 900), Visit 13 (Month 33; day 990), Visit 14 (Month 36; day 1080), Visit 15 (Month 39; day 1170), 
Visit 16 (Month 42; day 1260), and Visit 17 (Month 45; day 1350). 
b. 
Demographic, medical and medication history collected during SD-005 will be utilized as the baseline information for SD-006. 
c. 
The physical examination, as well as, height, weight, and temperature performed at the final visit for SD-005 will be utilized as the baseline assessment for SD-
006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case the assessment will be repeated. A complete physical examination, as well as, height, 
weight, and temperature will be performed at visit 18. 
d. 
The BSA assessments of lesional skin and wound burden performed at the final visit for SD-005 will be utilized as the baseline assessment for SD-006 unless 
Visit 1 is ≥ 14 days after the final SD-005 visit in which case the assessment will be repeated. The BSA assessments of lesional skin and wound burden will be 
performed at visits 2 through 18. 
e. 
If the target wound has not healed by the final visit of the SD-005 study, the target wound will be assessed in SD-006 using ARANZ until the wound has healed. 
The ARANZ picture and target wound area value determined at the final visit for SD-005 will be utilized as the baseline target wound area and picture for SD-
006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case the assessment will be repeated. If target wound has healed, assess for scarring. Target 
wound data was not captured in the M48/EOS visit 
f. 
The urine pregnancy test performed at the final visit for SD-005 will be utilized for entry into SD-006 if the visits occur on the same day. Otherwise, the urine 
pregnancy test will be performed at Visit 1 and at Visits 3 through 18. 
g. 
Ensure the patient is dispensed sufficient SD-101-6.0 until the next study visit. 
h. 
All AEs experienced in SD-005 should be noted in medical history for SD-006 at Visit 1 only. 


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 12 of 26 
6.2. 
Time Point Algorithms 
6.2.1. 
Study Day 
The date of informed consent/assent (Visit 1), will be considered study day 0. Days prior to study 
day 0 will be negative. Study days will be calculated as follows only when the full assessment 
date is known (ie, partial dates will have missing relative days). 
Study day will be calculated as follows: 
Date of Assessment – Date of Informed Consent. 
The relative day on study drug will be calculated as follows: 
Date of assessment – date of the first study drug administration +1. 
6.2.2. 
Windows 
For analysis purposes, the visit numbers will be allotted into windowed visits, as illustrated in 
Table 2.


Statistical Analysis Plan 
Final Version 2.0 
Protocol: SD-006 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
Page 13 of 26 
Table 2: 
Analysis Windows 
Week 
Visit 
Scheduled Study Day 
Visit Window for Analysis 
(Days) 
Screening/Baseline 
Visit 1 
0 
Day -13 to Day 0 
Month 1 
Visit 2 
30 
Day 1 – Day 60 
Month 3 
Visit 3 
90 
Day 61 – Day 135 
Month 6 
Visit 4 
180 
Day 136 – Day 225 
Month 9 
Visit 5 
270 
Day 226 – Day 315 
Month 12 
Visit 6 
360 
Day 316 – Day 405 
Month 15 
Visit 7 
450 
Day 406 – Day 495 
Month 18 
Visit 8 
540 
Day 496 – Day 585 
Month 21 
Visit 9 
630 
Day 586 – Day 675 
Month 24 
Visit 10 
720 
Day 676 – Day 765 
Month 27 
Visit 11 
810 
Day 766 – Day 855 
Month 30 
Visit 12 
900 
Day 856 – Day 945 
Month 33 
Visit 13 
990 
Day 946 – Day 1035 
Month 36 
Visit 14 
1080 
Day 1036 – Day 1125 
Month 39 
Visit 15 
1170 
Day 1126 – Day 1215 
Month 42 
Visit 16 
1260 
Day 1216 – Day 1305 
Month 45 
Visit 17 
1350 
Day 1306 – Day 1395 
Month 48/Final Visit 
Visit 18 
1440 
Day 1396 – Completion 
If two visits fall within the window, then the closest one will be selected. If two visits are equal 
distance from the nominal visit day, then the first one is used. 
6.3. 
Baseline Definition and Assessments 
6.3.1. 
Baseline definition 
For most cases, the baseline visit (Visit 1) will occur at Visit 5 for SD-005. Exceptions are 
detailed below. 
The Body Surface Area Index (BSAI) assessments of lesional skin and wound burden performed 
at the Visit 5 for SD-005 will be utilized as the baseline assessment for SD-006 unless Visit 1 is 
≥ 14 days after the final SD-005 visit in which case the assessment will be repeated. 
The urine pregnancy test performed at the final visit for SD-005 will be utilized for entry 
(Visit 1) into SD-006 only if the visits occur on the same day, otherwise, urine pregnancy test 
will be performed at Visit 1 as baseline assessment for SD-006. 


Statistical Analysis Plan 
 
Final Version 2.0 
Protocol: SD-006 
 
22 August 2018 
Scioderm Inc., An Amicus Therapeutics Company 
 
Page 14 of 26 
The physical examination performed at the final visit for SD-005 will be utilized as the baseline 
assessment for SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case a 
physical examination will be repeated and used as baseline assessment for SD-006. 
The ARANZ picture that documents target wound status at the final visit for SD-005 will be 
utilized to determine target wound area unless Visit 1 is ≥ 14 days after the final SD-005 visit, in 
which case the assessment will be repeated on the same wound.  For target wounds that are not 
closed by the end of Study SD-005, the ARANZ picture and calculation of target wound area at 
the final visit for Study SD-005 will be used as the baseline area size of the target wound for SD-
006. The wounds that are closed at the end of study SD-005 will not be followed up and 
analyzed. 
6.3.2. 
Baseline assessments 
The following screening and baseline assessments will be conducted prior to initial application 
of study treatment: 
 Informed consent/assent signed and dated. 
 Inclusion/exclusion assessment. 
Medical and medication history (including disease subtype) obtained from SD-005. 
Adverse events continuing in study SD-005 and those originating within the gap 
between studies SD-005 and SD-006 will be transcribed into Medical History. 
Note: All Adverse Events (AEs) experienced in SD-005 and medical events occurring 
between the end of SD-005 and the enrollment into SD-006 after completion of 
SD-005 should be noted in the medical history for SD-006 at Visit 1 only. 
 Demographics (date of birth, race, gender, ethnicity) obtained from SD-005. 
 Vital Signs (height/length, weight, temperature) obtained from final visit of SD-005 
unless Visit 1 is ≥ 14 days after the final SD-005 visit in which case the assessment 
will be repeated. 
 Physical examination obtained from final visit of SD-005 unless Visit 1 is ≥ 14 days 
after the final SD-005 visit in which case the assessment will be repeated. 
 BSAI of wound burden obtained from final visit of SD-005 unless Visit 1 is ≥ 14 days 
after the final SD-005 visit in which case the assessment will be repeated. 
 BSAI of lesional skin obtained from final visit of SD-005 unless Visit 1 is ≥ 14 days 
after the final SD-005 visit in which case the assessment will be repeated. 
 Assess target wound via ARANZ; if the target wound has not healed by the final visit 
of the SD-005 study, the same target wound will be assessed in SD-006 using 
ARANZ until the wound has healed. The ARANZ picture for target wound will be 
utilized as the baseline for SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 
visit in which case the assessment will be repeated. 
 If target wound has healed, assess for scarring. 
 Bandage history. 


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 The urine pregnancy test performed at the final visit for SD-005 will be utilized for 
entry (Visit 1) into SD-006 only if the visits occur on the same day, otherwise, urine 
pregnancy test will be performed at Visit 1 as baseline assessment for SD-006. 
 Dispense sufficient SD-101-6.0 until next study visit. 
6.4. 
Efficacy Assessments 
6.4.1. 
Change in Body Surface Area Index (BSAI) 
 Change in lesional skin based on BSA estimates at Month 1, 3, 6, 9, 12, 15, 18, 21, 
24, 27, 30, 33, 36, 39, 42, 45, and 48 compared to baseline will be measured using the 
Body Surface Area Index (BSAI), where change is defined as the corresponding 
month value minus the baseline value. 
 The BSAI is a global measure of disease extent 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. The BSAI of lesional skin will 
be assessed as listed in Section 11.1. 
 Change in total body wound coverage based on BSAI estimates at Months 1, 3, 6, 9, 
12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and 48 compared to baseline will be 
measured using the BSAI, where change is defined as the corresponding month value 
minus the baseline value. The BSAI of wounds will be assessed as listed in 
Section 11.2. Due to the termination of the study data at later time points will be 
limited. 
6.5. 
Safety Assessments 
6.5.1. 
Extent of Exposure and Compliance to Study Treatment 
SD-101-6.0 will be applied once a day to the entire body for a period of 1440 days. No daily use 
data are collected in this study. 
6.5.2. 
Adverse Events 
Treatment-emergent adverse events (TEAEs) are 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 adverse event (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. Treatment-emergent AEs will be collected after signing the informed 
consent/assent through the last study visit. If there is a gap between the completion of the Study 
SD-005 and the start of Study SD-006, adverse events starting after the last study day or 
changing in severity or relationship to treatment within the gap will be recorded in the medical 
history for study SD-006. Continuing adverse events will be also captured in medical history for 
the extension study SD-006. 
Medical review will take place to determine if any of AEs could be potentially related to the 
contamination of the study medication during the manufacturing process. The investigator’s 


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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 - the month. 
c. 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. 
6.5.3. 
Clinical Laboratory Evaluations 
The urine pregnancy test performed at the final visit for SD-005 will be utilized for entry 
(Visit 1) into SD-006 only if the visits occur on the same day, otherwise, urine pregnancy test 
will be performed at Visit 1. Urine pregnancy tests for female patients of child bearing potential 
(sensitivity at least 25 mIU/ml) will also be performed at Visit 3 through Visit 18. 
6.5.4. 
Physical Examination including Height/Length, Weight and Temperature 
The physical examination performed at the final visit for SD-005 will be utilized as the baseline 
assessment for SD-006 unless Visit 1 is ≥ 14 days after the final SD-005 visit, in which case a 
physical examination will be repeated. An additional physical examination will be done by a 
physician at Visit 18. 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.


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7. 
STATISTICAL METHODS 
7.1. 
General Methodology 
The final analysis after the study completion will be preceded by at least one interim analysis. 
Data will be summarized by treatment groups (based on 005 study treatment: Placebo –> 
SD-101-6.0 and SD-101-6.0 –> SD-101-6.0) and overall (where appropriate). Summary and 
analysis tables will include number of patients (n), mean, standard deviation, median, minimum, 
and maximum values for all continuous variables. When appropriate, two-sided 95% confidence 
intervals may be used. 
In summary tables of categorical variables counts and percentages will be presented. The 
denominator for each percentage will be the number of patients within the population (unless 
otherwise specified).  
All analyses for efficacy will be performed using the Intent-To-Treat (ITT) population, all safety 
analyses will be performed using the safety population. No comparison between treatment 
groups will be performed. The comparison to baseline will be done by visit in Placebo –> 
SD-101-6.0 group. All hypothesis testing will be two-sided. P-values less than 0.001 will be 
reported as <0.001 in summary tables. 
All statistical analysis will be performed using SAS® v9.2 or higher. 
7.2. 
Adjustments for Covariates 
No covariates are planned to be used in the analyses for this study. 
7.3. 
Handling of Dropouts or Missing Data 
Dropout patients will not be replaced in this study. Missing data will not be imputed unless 
specified otherwise in the following section. 
7.4. 
Multi-center Studies and Pooling of Centers 
Data will be pooled across all study sites. The justification for pooling is made on the basis of 
three important factors: 1) all study sites use one common protocol, 2) sites are actively and 
adequately monitored to ensure protocol compliance, 3) all sites use a common data reporting 
method and data collection procedures(1). 
7.5. 
Multiple Comparisons/Multiplicity 
No multiple comparisons and multiplicity adjustment will be used for this study. 
7.6. 
Examination of Subgroups 
Safety summaries will be presented by subgroups of gender, age (28 days to <2 years, 2 years to 
<12 years, 12 years to <= 18 years, >18 years).,  


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8. 
STATISTICAL ANALYSIS 
8.1. 
Disposition of Patients 
The number and percentage of patients who were enrolled, treated, and completed the study will 
be summarized. Similar summaries will be provided for those patients who discontinued from 
the study prematurely. For those patients who discontinue early, the reasons for discontinuing 
will also be summarized. The disposition of all patients will be listed.  
Data on screening failures (patients who signed informed consent but were not entered into the 
trial) will be collected with a yes or no on the CRF and will be presented in a listing. 
8.2. 
Protocol Deviations 
Number and percentage of patients with major protocol deviations will be summarized for the 
ITT population. A final list of patients who have any major protocol deviations will be 
documented before interim and final database locks. A listing of patients with major protocol 
deviations will be provided.  
8.3. 
Analysis Populations 
8.3.1. 
Intent-to-Treat (ITT) Population 
The intent-to-treat (ITT) population will be defined as all patients who have rolled over from 
SD-005. 
8.3.2. 
Safety Population 
The safety population is defined as all randomized patients who applied/were administered the 
study medication at least once. 
The Intent-to-Treat (ITT) population will be used for all efficacy analyses. The Safety population 
will be used for all safety analyses. The Per Protocol (PP) population will be used for supportive 
analyses of the efficacy endpoints. 
If the Safety population and ITT populations are identical, then the efficacy and safety analyses 
will be performed using the ITT population only. 
8.4. 
Demographic and Other Baseline Characteristics 
Descriptive summaries of demographic and baseline characteristics will be presented for the ITT 
Population.  
Continuous variables such as patient age, weight, height, body mass index (BMI), BSAI (for 
lesion and wound burden), and temperature will be summarized as described previously. 
Categorical variables such as patient gender, , age group (28 days to <2 years, 2 years to <12 
years, 12 years to < 18years, 18 years to < 65 years, 65 years to <85 years,  >=85 years), EB 
type, and baseline target wound size (=0, >0) will be summarized using number of observations 
and percentages for each category. 
Enrollment by country will be summarized. 
Medical history, including disease history will be summarized and listed. 


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8.5. 
Prior and Concomitant Therapy 
The World Health Organization (WHO) Drug Dictionary will be used to classify medications for 
the purpose of the first interim analysis. The WHO Drug Dictionary version might be updated in 
the future analyses and if so it will be properly footnoted on all tables and listings. Any 
medication taken before and continuing after first application of SD-101-6.0 in the study SD-006 
is considered a concomitant medication. Any medication given before first application but 
discontinued prior to first application 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 patients who had previous therapies/medications by 
Anatomical Therapeutic Chemical (ATC) code text and WHO drug name 
2. Number and percentage of patients who had concomitant therapies/medications by ATC 
text and WHO drug name 
 
 


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8.6. 
Analysis of Efficacy Parameters 
8.6.1. 
Analysis of BSAI 
No comparison between treatment groups will be performed. The comparison to baseline will be 
done by visit in Placebo –> SD-101-6.0 group using the paired t-test. 
 Change in extent of lesional skin based on BSAI at each visit compared to baseline. 
To evaluate post-baseline BSAI of lesional skin, both change from baseline and 
percentage change from baseline will be explored using descriptive statistics. Change 
from baseline will be calculated as the post-baseline measurement minus the baseline 
value. Percentage change from baseline will be calculated as the change from 
baseline divided by the baseline value times 100. 
Graphs of the mean change and mean percentage change from baseline over time will 
also be presented. 
 Change in total wound burden based on BSAI at each visit compared to baseline. 
This assessment will be analyzed using the same approach for lesional skin as the 
total body wound burden to both change from baseline and the percentage change 
from baseline. 
Graphs of the mean change and mean percentage change from baseline over time will 
also be presented. 
8.7. 
Analysis of Safety 
8.7.1. 
Extent of Exposure  
No diary data were collected on whether a patient used or did not use SD-101-6.0 on a given day. 
Therefore the number of days on the study will be considered number of days of exposure. It will 
be summarized using descriptive statistics by overall. Descriptive statistics will also be provided 
for duration of exposure into categorical summary of <30, >=30 to <90, >=90 to <180, >=180 to 
<1 year, >=1 year to <2 years, >=2 years.  
8.7.2. 
Adverse Events by Preferred Term and System Organ Class  
For the first interim analysis serious AEs will be mapped to system organ class (SOC) and 
preferred terms (PTs) using the 19.1 version of MedDRA. 
If there is a gap between the completion of the study SD-005 and the start of the study SD-006, 
adverse events starting after the last study day or changing the severity or relationship to 
treatment within the gap will be counted as medical history for the extension study SD-006. 
Continuing adverse events will also be captured in medical history for the extension study 
SD-006. If the severity or relationship to treatment changed on or after the first dose of study 
medication, then that AE is considered a TEAE after that change.  
If an AE stared after signing an informed consent/assent but before the first dose of study 
medication was taken in the study SD-006, then such an AE is non treatment-emergent. 


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8.7.3. 
Summaries of Adverse Event Incidence Rates for All Patients 
The number and percentage of patients who experienced TEAEs will be presented by SOC and 
by PT within SOC for each treatment group. Treatment-emergent AEs (TEAEs) will be similarly 
presented by severity (mild, moderate, severe), by relationship to study drug (unrelated, definite, 
probable, and possible) and by outcome of events. Additionally, the number of TEAEs (as 
opposed to the number and percentage of patients) will be presented by treatment group.  
The number of patients with TEAEs and number of TEAEs will also be presented by the 
following subgroups of Age (28 days to <2 years, 2 years to <12 years, 12 years to <=18 years, 
>18 years). Subgroups for age are defined based at the patient’s age at Baseline. 
To count the number of patients who experienced each TEAE, a patient experiencing the same 
TEAE multiple times will only be counted once for the corresponding PT. Similarly, if a patient 
experiences multiple TEAEs within the same SOC, the patient will be counted only once for that 
SOC. If a patient 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 patient experienced more than one TEAE, the worst 
outcome will be counted under that patient. If a patient experienced more than one outcome 
within a SOC (or PT), the patient 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 patient 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).  
Additionally, the incidence and the number of non-serious TEAEs will be presented by treatment 
group. 
Non treatment-emergent AEs, if any, will be listed. 
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: 
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. 
3. 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 the month. 


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c. If the Day and Month are missing then impute Day and Month as the Day and Month 
of the first study drug application. 
4. 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. 
5. 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. 
6. 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. 
7. 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 patient 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 treatment 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 Incidence Rates for Serious Adverse Events (SAE), 
Adverse Event Dropouts, and Death 
During the treatment period, the number and percentage of patients who experienced TESAEs 
and separately TEAEs leading to withdrawal from the study will be presented by SOC and by PT 
within each SOC for each treatment. Treatment-emergent SAEs and 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 patients) and separately TEAEs leading to withdrawal will be presented.  
Number of patients with TESAEs and separately TEAEs resulting in withdrawal as well as 
number of TESAEs and separately the number of TEAEs leading to withdrawal will also be 
presented by the following subgroups of Age (28 days to <2 years, 2 years to <12 years, 12 years 
to <=18 years, >18 years), EB type and independently. Subgroups for age are defined based at 
the patient’s age at Baseline.  
In case that there are non-treatment emergent serious adverse events, they will be listed. 


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A listing of all serious adverse events and discontinuations due to AEs will be included. Patient 
with deaths, SAEs or patients who withdraw due to AE will be listed separately and discussed 
with patient narratives.  
8.7.6. 
Discontinuation from the Study 
Number of patients who discontinued from the study and reasons for discontinuation will be 
summarized. 
8.7.7. 
Clinical Laboratory Evaluations 
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 metric units. 
8.7.8.2. 
Physical 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. Baseline is defined in section 6.3. 
9. 
COMPUTER SOFTWARE 
All analyses will be performed by FMD K&L Inc. using Version 9.2 or later of SAS® software. 
All summary tables, data listings and figures will be prepared utilizing SAS® software. 
The standard operating procedures (SOPs) of FMD K&L Inc. will be followed in the creation 
and quality control of all data displays and analyses. 


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10. 
REFERENCES 
1) 
Meinert, C. Clinical Trials: Design, Conduct, and Analysis. (1986). Oxford University 
Press. New York, NY 


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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.