Conditions: Atopic Dermatitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 102
Healthy volunteers: no

Brief summary:
This study will compare the safety and efficacy of Oral DS107 (2 g) to placebo in patients with moderate to severe atopic dermatitis.

Oral DS107 (2 g) will be orally administered for 8 weeks, and will be compared against placebo.

This study will enroll approximately 100 adult patients.

Detailed description:
Subjects will come to the clinic on 6 occasions: at screening, baseline, week 2, week 4, week 8 (end of treatment/early termination) and week 10 (follow-up). The primary efficacy variable will be the IGA. Secondary efficacy variables will include IGA (Investigator's Global Assessment), SCORAD (Scoring Atopic Dermatitis) Visual Analog Scale (VAS), EASI, BSA (Body Surface Area), POEM (Patient Orientated Eczema Measure), DLQI (Dermatology Life Quality Index).

Arms:
arm 1: Oral DS1072g, 4 x 500mg capsules administered orally once a day arm 2: Placebo capsules matching Oral DS107 capsules

Interventions: intervention 1: Oral DS107 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document:
Prot_000.pdf: 
Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 1 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
 
 
 
 A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II STUDY 
TO ASSESS THE EFFICACY AND SAFETY OF ORALLY ADMINISTERED DS107G 
TO PATIENTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS 
  
 
PROTOCOL # DS107G-02 
 
 
Final 
 
VERSION 2.2 
22 July 2015 
 
 
Previous version number: 1.0  28 Jul 2014 
 
 
 
 
2.0 12 Nov 2014 
 
 
 
 
2.1 13 Mar 2015 
 
Sponsor: 
 
 
 
Dignity Sciences Ltd,  
           
 
 
 
Trintech Building, South County Business Park, 
          
 
 
 
Leopardstown, Dublin 18, 
          
 
 
 
Republic of Ireland 
           
 
 
 
Tel.: 00353 (1) 2933590 
 
Sponsor Medical Advisor:   
Prof. Dr. med. Diamant Thaci 
 
 
Comprehensive Center For Inflammation Medicine 
 
 
Universität zu Lübeck 
 
 
Ratzeburger Allee 160, 23538 Lübeck, 
 
 
Germany 
 
Medical Monitoring:  
 
Safety Physician 
Product Life Ltd, 
The Jeffreys Building, 
St. John’s Innovation Park, 
Cowley Road, 
Cambridge CB4 0DS, United Kingdom 
Tel.: +44 (0) 1223 402660 
 
Email: safety@productlife-group.com 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 2 of 49 
Protocol version 2.2: 22 July 2015 
 
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TABLE OF CONTENTS 
 
PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE .................................................................. 7 
LIST OF ABBREVIATIONS........................................................................................................................... 8 
SUMMARY .................................................................................................................................................. 10 
1 
BACKGROUND .................................................................................................................................. 14 
1.1 
Atopic Dermatitis ........................................................................................................................ 14 
1.2 
DS107G ..................................................................................................................................... 14 
1.3 
Rationale for this study .............................................................................................................. 15 
2 
STUDY HYPOTHESIS AND OBJECTIVES ....................................................................................... 16 
3 
STUDY ENDPOINTS ......................................................................................................................... 16 
3.1 
Primary Endpoint ............................................................................................................................ 16 
3.2 
Secondary Endpoints ..................................................................................................................... 16 
3.3 
Exploratory Endpoints .................................................................................................................... 16 
4 
STUDY DESIGN ................................................................................................................................. 17 
5 
STUDY POPULATION ....................................................................................................................... 17 
5.1 
Inclusion Criteria ............................................................................................................................ 17 
5.2 
Exclusion Criteria ........................................................................................................................... 18 
5.3 
Study Restrictions .......................................................................................................................... 19 
5.4 
Discontinuations ............................................................................................................................. 19 
6 
TREATMENT ...................................................................................................................................... 21 
6.1 
Treatment Administration ............................................................................................................... 21 
6.2 
Study Treatment ............................................................................................................................. 22 
6.2.1 
Description ............................................................................................................................. 22 
6.2.2 
Storage Conditions ................................................................................................................ 22 
6.2.3 
Study Drug Dispensing and Return ....................................................................................... 22 
6.2.4 
Drug Accountability ............................................................................................................... 22 
6.2.5 
Method of Assignment to Treatment ..................................................................................... 23 
6.2.6 
Rationale for Selection and Timing of Doses in the Study .................................................... 23 
6.2.7 
Breaking of Study Blinding .................................................................................................... 23 
6.3 
Concomitant Therapy ..................................................................................................................... 24 
6.3.1 
Permitted therapies ............................................................................................................... 24 
6.3.2 
Prohibited therapies or procedures ....................................................................................... 25 
6.3.3 
Assessment of Compliance ................................................................................................... 25 
7 
STUDY PROCEDURES ..................................................................................................................... 26 
7.1 
Screening, Visit 1 (Day -30 to -1) ................................................................................................... 26 
7.2 
Baseline, Visit 2 (Day 0) ................................................................................................................. 26 
7.3 
Week 2, Visit 3 (Day 14 ± 2 days) .................................................................................................. 27 
7.4 
Week 4, Visit 4 (Day 28 ± 2 days) .................................................................................................. 27 
7.5 
Week 8, Visit 5 (Day 56 ± 2 days) (End of Treatment/Early Termination Visit) ............................. 28 


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7.6 
Follow-up/Week 10, Visit 6 (Day 70 ± 3 days) ............................................................................... 28 
7.7 
Early termination visit ..................................................................................................................... 29 
8 
STUDY ASSESSMENTS ................................................................................................................... 29 
8.1 
Efficacy Assessments .................................................................................................................... 29 
8.1.1 
Investigator’s Global Assessment (IGA) ............................................................................... 29 
8.1.2 
Eczema Area and Severity Index (EASI) .............................................................................. 29 
8.1.3 
Body Surface Area (BSA) ...................................................................................................... 29 
8.1.4 
SCORing Atopic Dermatitis (SCORAD) ................................................................................ 29 
8.1.5 
Visual Analog Scale of Pruritus ............................................................................................. 30 
8.1.6 
Patient-Oriented Eczema Measure (POEM) ......................................................................... 30 
8.1.7 
Dermatology Quality of Life (DLQI) Questionnaire ................................................................ 30 
8.1.8 
Transepidermal Water Loss (TEWL) (at selected sites only) ................................................ 30 
8.2 
Safety Assessments ....................................................................................................................... 31 
8.2.1 
Vital Signs .............................................................................................................................. 31 
8.2.2 
Physical Examination ............................................................................................................ 31 
8.2.3 
Clinical Laboratory Tests ....................................................................................................... 31 
8.2.4 
Total and Free DGLA plasma levels, Total Fatty Acid Profile and Interleukins levels .......... 32 
9 
ADVERSE EVENTS ........................................................................................................................... 33 
9.1.1 
Adverse Events Causality ..................................................................................................... 33 
9.1.2 
Adverse Events Severity ....................................................................................................... 33 
9.1.3 
Serious Adverse Events ........................................................................................................ 34 
9.1.4 
SAE Reporting: ...................................................................................................................... 34 
9.2 
Pregnancy Reporting ..................................................................................................................... 35 
10 
DATA QUALITY ASSURANCE/SITE MONITORNG ......................................................................... 35 
11 
DATA COLLECTION AND RETENTION ........................................................................................... 35 
12 
CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT RECORDS ..................................... 36 
13 
INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS .............................................................. 36 
14 
SAMPLE SIZE AND STATISTICAL METHODS ................................................................................ 37 
14.1 
Determination of Sample Size ................................................................................................... 37 
14.2 
Statistical and Analytical Plans .................................................................................................. 37 
14.2.1 
Subject Disposition............................................................................................................ 37 
14.2.2 
Efficacy analysis ................................................................................................................ 37 
14.2.3 
Safety Analysis .................................................................................................................. 38 
15 
ETHICS .............................................................................................................................................. 38 
15.1 
Local Regulations/Declaration of Helsinki ................................................................................. 38 
15.2 
Ethical Review ........................................................................................................................... 39 
15.3 
Informed Consent ...................................................................................................................... 39 
16 
PUBLICATION POLICY ..................................................................................................................... 39 
17 
REFERENCES ................................................................................................................................... 39 
18 
APPENDIX A  Study Flow Chart ........................................................................................................ 41 
19 
APPENDIX B – INVESTIGATOR’S GLOBAL ASSESSMENT .......................................................... 43 
20 
APPENDIX C - Eczema Area and Severity Index (EASI) .................................................................. 44 
21 
APPENDIX D - SCORing Atopic Dermatitis (SCORAD) .................................................................... 45 


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22 
APPENDIX E - Patient-Oriented Eczema Measure (POEM) ............................................................. 46 
23 
APPENDIX F – Dermatology Life Quality Index (DLQI) ..................................................................... 47 
24 
APPENDIX G - Diagnostic Criteria for Atopic Dermatitis ................................................................... 49 
 
 


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Confidential and property. Permission should be obtained before any reproduction. 
PROTOCOL SUMMARY OF CHANGES 
Amendment 
Rational for amendment 
Major changes to the protocol 
V2.1 / 13 
MAR 2015 
 
 
 
V2.2 / 22 
JUL 2015 
 
1) Addition of later testing for interleukins 
blood levels. 
 
 
 
1) In the case where the subject ends the 
study before completion and has an early 
termination visit, the subject will also 
return for the safety assessments listed at 
Week 10, two weeks after the early 
termination visit.  
 
 
 
 
 
 
 
 
 
 
2) Adjustment of the statistical analysis for 
the primary endpoint to take into account 
the stratification by site included in the 
randomization. 
 
 
 
 
 
3) Change in the evaluation of the impact 
of missing values on the primary 
endpoint.  
  
 
1) Interleukin evaluation was added in the 
following sections: Endpoints (page 17), 
study procedures (pages 26-28), safety 
assessments (page 32) and study flow chart 
(page 41). 
 
1) The Week 10 safety assessments for the 
subject 
who 
ends 
the 
study 
before 
completion  will include (added in the 
Discontinuations section/pages 19-20): 
- Concomitant medications 
- Safety labs (only if there was a clinically 
significant change from baseline at the 
Week 8 / ET visit)  
- Urine pregnancy test, if female of 
childbearing potential 
- Vital signs  
- Physical exam  
- Adverse events 
The Study Flow Chart was updated 
accordingly (page 41). 
 
2) Cochran-Mantel-Haenszel test with site 
as a stratification factor will be used for the 
statistical analysis instead of the chi-square 
test to compare between groups for the 
primary endpoint. A supportive analysis will 
be performed using a Fisher’s exact test.  
(was added in the Efficacy analysis 
section/page 37). 
 
3) Supportive analysis using the last 
observation carried forward (LOCF) will be 
performed instead of the tipping point 
analysis. (was added in the Efficacy 
analysis section/page 37). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




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PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
Investigator name:  
 
 
Signature: 
 
Date:  
 
 
 
 
 
 
 
Institution Name: 
 
 
 
 
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) procedures, 
instructions from Innovaderm Research representatives, the Declaration of Helsinki, 
International Conference on Harmonization (ICH) Good Clinical Practices 
Guidelines, applicable Canadian regulations, U.S. federal regulations, and local 
regulations governing the conduct of clinical studies. 
 
 
 
 


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LIST OF ABBREVIATIONS 
 
15 HETrE 
15 hydroxyeicosatrienoic acid  
AD 
Atopic dermatitis 
AE 
Adverse Event/Adverse Experience 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
COX 
Cyclooxygenase 
CRF 
Case Report Form 
DGLA 
Dihomo-gamma-linolenic acid 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
ECRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLA 
Gamma-linolenic acid 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IMP 
Investigational medicinal product 
ITT 
Intent-to-treat 
IRB 
Institutional Review Board 
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web Response System 
LOCF 
Last observation carried forward 
LPO 
Lipoxygenase 
MedDRA © 
Medical Dictionary for Regulatory Activities 
PGE 
Prostaglandine E 
POEM 
Patient Oriented Eczema Measure 
PP 
Per Protocol 
PUVA 
Psoralen and Ultra Violet A  
REB 
Research Ethics Board 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
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Confidential and property. Permission should be obtained before any reproduction. 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOC 
System Organ Classification 
SCORAD 
SCORing of Atopic Dermatitis 
TEWL 
Trans Epithelial Water Loss 
UV, UVA, UVB 
Ultra Violet (A or B) 
VAS 
Visual Analog Scale 
 
 
 
 
 


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SUMMARY  
 
Title: 
A Randomised, Double-blind, Placebo-Controlled, Phase II Study to Assess 
the Efficacy and Safety of orally administered DS107G to Patients with 
Moderate to Severe Atopic Dermatitis 
  
Phase: 
 IIa 
 
Population: 
Approximately 100 male or female subjects, aged 18 years or older, moderate to 
severe atopic dermatitis will be included in this study. 
 
Number of Sites: 
Approximately 20 centers in Canada and US will participate in this study  
 
Study Duration: 
10 to 14 weeks including screening and follow-up 
 
Hypothesis: 
DS107G is superior to placebo for improvement of IGA score in patients with 
moderate to severe atopic dermatitis. 
 
Objectives:  
 
Primary objective:  
To compare the efficacy of orally administered DS107G capsules versus placebo, in the treatment of adult 
patients with moderate to severe atopic dermatitis. 
 
Secondary objective: 
To assess the safety of orally administered DS107G capsules versus placebo, in adult patients with 
moderate to severe atopic dermatitis. 
 
 
Endpoints: 
 
Primary Endpoint 
 
Proportion of patients achieving an IGA (Investigator Global Assessment) of 0 (clear) or 1 (almost clear) 
and a decrease of at least 2 points in IGA at Week 8. 
 
Secondary Endpoints 
 
o 
Change from baseline in IGA at week 2, 4 and 8. 
 
o 
Change from baseline in EASI (Eczema Area and Severity Index) at week 2, 4 and 8. 
 
o 
Proportion of patients achieving at least a 1-point decrease in IGA at week 8 
 
o 
Change from baseline in the Patient Orientated Eczema Measure (POEM) at week 2, 4 
and 8. 
 
o 
Change from baseline in the Dermatology Life Quality Index (DLQI) score at week 2, 4 
and 8. 
 
o 
Change from baseline in SCORAD at week 2, 4 and 8. 
 


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o 
Change from baseline in the patient’s Visual Analog Scale (VAS) pruritus score at Week 
2, 4 and 8. 
 
o 
Change from baseline in Body Surface Area (BSA) at Week 2, 4 and 8. 
 
o 
Number of treatment-emergent adverse events (TEAEs) in each treatment group. 
 
Exploratory Endpoints 
 
o 
Change from baseline in Trans epidermal water loss (TEWL) at week 2, 4 and 8 
(selected sites only). 
 
o 
Plasma total and free DGLA concentrations at Baseline, weeks 4 and 8. 
 
o 
Plasma total fatty acid profile at Baseline, week 4 and week 8 (sample to be retained and 
analyzed at a later date). 
 
o 
Interleukin profile at Baseline, week 4 and week 8 (Sample to be retained and analyzed 
at a later date).  
 
Overall Study Design 
 
Approximately 100 patients with moderate to severe atopic dermatitis will be included in this multicenter, 
double-blind, placebo controlled, phase IIa study. All subjects will sign an informed consent and undergo 
screening for study eligibility. Subjects will be randomized (1:1) at baseline visit to either receive oral 
DS107G 2 g, or placebo once daily for 8 weeks in a fasting state.  
 
Subjects will come to the clinic on 6 occasions: at screening, baseline, week 2, week 4, week 8 (end of 
treatment/early termination) and week 10 (follow-up). All subjects will exit the study at the Week 10 visit. 
The primary efficacy variable will be the proportion of patients achieving an IGA of 0 (clear) or 1 (almost 
clear) and a decrease of at least 2 points in IGA at week 8. Secondary efficacy variables will include IGA 
at other visits, pruritus (obtained from the SCORAD visual analog scale), EASI, BSA, POEM, DLQI, 
SCORAD and TEWL (for selected sites only). Safety will be assessed through adverse events, physical 
examination, vital signs and safety laboratory tests (including pregnancy tests for women of childbearing 
potential). Pharmacokinetic samples will be obtained at Baseline (Day 0), week 4 and week 8 visits in order 
to measure total and free DGLA plasma trough levels.  Separate plasma samples will be retained for later 
analysis of total fatty acid profile and interleukin profile. 
 
Inclusion Criteria 
1. Male or female subject aged 18 years and older on the day of signing the informed consent form 
(ICF). 
 
2. Clinically confirmed diagnosis of active atopic dermatitis according to Hanifin and Rajka criteria 
(Appendix G). 
 
3. Moderate to severe atopic dermatitis at baseline as defined by an IGA of minimum 3 at baseline 
visit. 
 
4. Atopic dermatitis covering minimum 10% of the body surface area at baseline. 
 
5. Body mass index (BMI) is between 18 and 35 kg/m2 inclusively. 
 
6. Female patients of childbearing potential must use adequate contraception or have a sterilized 
partner for the duration of the study: systemic hormonal contraceptives, intrauterine device or 
barrier method of contraception in conjunction with spermicide, or agree to sexual abstinence. 


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Hormonal contraceptives must be on a stable dose for at least one month before baseline. Note: 
Women of non-child bearing potential are;  
 
- 
women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or 
tubal ligation) 
- 
women greater than 60 years of age  
- 
women greater than 40 and less than 60 years of age who have had a cessation of menses 
for at least 12 months and a follicle-stimulating hormone (FSH) test confirming non-
childbearing potential (FSH ≥40 mIU/mL) or cessation of menses for at least 24 months 
without FSH levels confirmed.  
 
7. Patients who are able and willing to stop treatment for atopic dermatitis throughout the study 
(except for allowed emollients; see Section 6.3.1). 
 
8. Capable and willing to give signed informed consent and the consent must be obtained prior to 
any study related procedures. 
 
Exclusion Criteria 
1. Female patients with positive pregnancy test at screening or Day 0 visit (baseline) or lactating women. 
2. Any clinically significant controlled or uncontrolled medical condition or laboratory abnormality that 
would, in the opinion of the investigator, put the patient at undue risk or interfere with interpretation of 
study results.  
3. Clinically significant impairment of renal or hepatic function. 
4. Other skin conditions that might interfere with atopic dermatitis diagnosis and/or evaluation (such as 
psoriasis or current viral, bacterial and fungal skin infections). 
5. History of hypersensitivity to any substance in DS107G or placebo capsules. 
6.  Use of biologics 3 months prior to start of treatment/ Day 0 visit (baseline), or 5 half-lives (whichever 
is longer). 
7. Use of systemic treatments (other than biologics) that could affect atopic dermatitis less than 4 weeks 
prior to baseline visit (Day 0), e.g. retinoids, calcineurin inhibitors, methotrexate, cyclosporine, 
hydroxycarbamide (hydroxyurea), azathioprine and oral/injectable corticosteroids; Intranasal 
corticosteroids and inhaled corticosteroids for stable medical conditions are allowed. 
8. Treatment with any experimental drug within 30 days prior to Day 0 visit (baseline), or 5 half-lives 
(whichever is longer). 
9. Excessive sun exposure, use of tanning booths or other ultraviolet (UV) light sources 4 weeks prior to 
Day 0 visit (baseline) and/or is planning a trip to sunny climate or to use tanning booths or other UV 
sources between screening and follow-up visits. 
10. Use of any topical medicated treatment for atopic dermatitis 2 weeks prior to start of treatment/Day 0 
visit (baseline), including but not limited to, topical corticosteroids, calcineurin inhibitors, tars, bleach, 
antimicrobials and bleach baths. 
 
11. Use of topical products containing urea, ceramides or hyaluronic acid 2 weeks prior to Day 0. 
 
12. Use of anti-histamines for atopic dermatitis within 2 weeks of baseline.  
13. Significant uncontrolled cardiovascular (a history of ECG abnormalities that are clinically significant in 
the opinion of the investigator), neurologic, malignant, psychiatric, respiratory or hypertensive disease, 
as well as diabetes and arthritis. 
14. Medical history of chronic infectious disease (e.g., hepatitis B, hepatitis C or infection with human 
immunodeficiency virus). 


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15. History of clinically significant drug or alcohol abuse in the last year prior to Day 0 (baseline). 
 
 
Statistical Analysis 
 
Continuous variables will be summarized in tables and will include the number of subjects, mean, standard 
deviation, median, minimum, maximum and inter-quartile range. Categorical variables will be presented in 
tables as frequencies and percentages. 
 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, unless otherwise 
specified. 
 
 
 


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1 BACKGROUND 
1.1 Atopic Dermatitis 
Atopic dermatitis is a chronic inflammatory skin disorder characterized by the presence of pruritus, papules, 
lichenification, excoriations, xerosis and oozing (1). The prevalence of AD has increased in the last few 
decades, affecting up to 20 percent of young children with the majority of cases starting in children younger 
than 5 years of age. Most cases improve by adulthood. The prevalence of atopic dermatitis in adults has 
been reported to be 1–3% (2-4) but more recent reports suggest that it may be much higher (5)(Silverberg 
JI). Atopic dermatitis can have a significant impact on morbidity and quality of life because of loss of sleep 
caused by pruritus, and the social stigma of a visible skin condition.  
 
AD is a multifactorial disease, with genetics, environment, and impaired immune response being the 
predominant factors (1, 6). Dendritic cells, T lymphocytes, macrophages, keratinocytes, mast cells, and 
eosinophils all play a role in AD by releasing proinflammatory cytokines and chemokines which induce the 
inflammatory response characteristic of atopic dermatitis lesions (7). 
 
Most of currently approved treatments for AD are topical and include corticosteroids, pimecrolimus and 
tacrolimus (8). Corticosteroids have been the mainstay of treatment for AD and different potencies and 
formulations are available. Topical corticosteroids are effective for the treatment of AD but their use is 
limited by the potential for local side effects such as skin atrophy and striae, Systemic absorption of 
corticosteroids can also induce diabetes, cataracts, osteoporosis and suppression of the hypothalamic 
pituitary axis. In addition, transient improvement is often followed by a rebound flare-up on discontinuation 
of treatment. Other treatments available include topical calcineurin inhibitors (eg, pimecrolimus, tacrolimus), 
and coal tar preparations. Cases of lymphoma have been reported in patients treated with calcineurin 
inhibitors. Patients with more severe disease are treated with ultraviolet B and A phototherapy or oral agents 
such as corticosteroids, cyclosporine, mycophenolate mofetil, methotrexate and azathioprine (9). There is 
a need for the development of novel treatments for atopic dermatitis.  
 
1.2 DS107G  
Dihomo-gamma-linolenic acid (DGLA) is an essential fatty acid found naturally in the body as the 2-carbon 
elongation product of gamma-linolenic acid (GLA). DGLA has a wide range of desirable biological effects. 
DGLA is metabolized by cyclooxygenase (COX) and lipoxygenase (LPO) enzymes to form eicosanoids, 
prostaglandins (PG) of the 1 series and also hydroxyl-fatty acid as 15 hydroxyeicosatrienoic acid DGLA 
(15 HETrE).  
 
DGLA is present in the human diet at levels up to 0.115 g per measure (10, 11). DGLA is also present in 
breast milk, with recorded levels ranging from 0.44% at Week 6 of lactation to 0.27% at Week 30 of lactation 
(12). DGLA is a ubiquitous constituent of normal tissues with a very benign safety profile when dosed to 
high levels. This is supported by the results of toxicity studies on orally administered DGLA published in the 
scientific literature and by recently completed preclinical and clinical studies which have shown no safety 
concerns. A number of pre-clinical studies with oral DGLA were described by Kawashima et al(13). These 
showed that DGLA had very low oral toxicity (LD50 more than 10 000 mg/kg), which is consistent with 
experience and expectation for other lipids of this class.  
 
Oral DGLA has been successfully dosed in healthy human subjects, at doses of up to 450 mg/day for up to 
four weeks, without any adverse effects or changes to blood biochemical parameters (14, 15). The content 
of DGLA in serum phospholipids was dose dependent, returning to baseline after a 4-week washout period. 
There were also no notable differences in serum lipid concentrations or any adverse signs related to 
treatment (14). 
 


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Based on the wide range of desirable biological effects observed for GLA, DGLA and its metabolites on 
inflammation and skin function (16-20), there is a clear rationale for development of DGLA as a treatment 
for inflammatory skin diseases. 
 
Oral DGLA (DS107G) administered to healthy volunteers in a Phase I trial (DS107G-01) as a single 500-, 
1000-, 2000-, or 4000-mg dose under fasted conditions; as a single 1000-mg dose under fed conditions; 
and as multiple 2000- and 4000-mg doses taken once daily for 28 consecutive days was well tolerated. The 
most common TEAE was diarrhea (reported as ‘loose stools’) which was mild to moderate in severity and 
of relatively short duration. The plasma pharmacokinetics of free and total DGLA were linear with single 
doses, but may be saturable with repeated doses or high concentrations. Plasma concentrations of free 
and total DGLA achieved steady-state by approximately Day 14. Free DGLA distributes well into skin: skin 
blister fluid concentrations were similar to plasma concentrations after about Day 8 of repeated dosing. 
Total DGLA concentrations are higher in plasma than in skin; the distribution to skin may be saturable. 
 
For more information on DS107G, refer to the most recent version of the investigator brochure.  
 
1.3 Rationale for this study 
 
Both DGLA and its metabolites have been shown to have various anti-inflammatory effects in the body 
(21). With advancement of purification technologies of fatty acids, purified DGLA is now available. The 
technology involves purifying GLA from plant oils such as borage oil and then converting to DGLA by 
adding two carbons. 
 
Supplementation of human or guinea pig diets with evening primrose or borage oil (vegetable oils that 
contain GLA) raises epidermal PGE1 concentrations. Evening primrose oil has been used in the clinical 
management of inflammatory disorders of the skin, including inflammation due to acne and atopic 
d ermatitis, and its reported beneficial effects may be due, at least in part, to epidermal generation of 
PGE1 & 15-HETrE from elevated tissue DGLA concentrations (22). This is supported by a recent study 
showing that clinical efficacy of evening primrose oil in AD is correlated with plasma levels of DGLA. In 
murine models, administration of DGLA also prevents the development of AD (23). 
 
This study will compare the safety and efficacy of one daily dose of DS107G (2g) to placebo in patients 
with moderate to severe atopic dermatitis.  
 
 


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2 STUDY HYPOTHESIS AND OBJECTIVES 
Hypothesis:  
 
DS107G is superior to placebo for improvement of IGA score in patients with moderate to severe atopic 
dermatitis. 
 
Primary objective:  
 
To compare the efficacy of orally administered DS107G capsules versus placebo, in the treatment of adult 
patients with moderate to severe atopic dermatitis. 
 
Secondary objective: 
 
To assess the safety of orally administered DS107G capsules versus placebo, in adult patients with 
moderate to severe atopic dermatitis. 
 
3 STUDY ENDPOINTS 
3.1 Primary Endpoint 
 
 
Proportion of patients achieving an IGA (Investigator Global Assessment) of 0 (clear) or 1 (almost 
clear) and a decrease of at least 2 points in IGA at Week 8. 
3.2 Secondary Endpoints 
 
 
Change from baseline in IGA at week 2, 4 and 8. 
 
 
Change from baseline in EASI (Eczema Area and Severity Index) at week 2, 4 and 8.  
 
 
Proportion of patients achieving at least a 1-point decrease in IGA at week 8. 
 
 
Change from baseline in the Patient Orientated Eczema Measure (POEM) at week 2, 4 and 8. 
 
 
Change from baseline in the Dermatology Life Quality Index (DLQI) score at week 2, 4 and 8. 
 
 
Change from baseline in SCORAD at week 2, 4 and 8. 
 
 
Change from baseline in the patient’s Visual Analog Scale (VAS) pruritus score at Week 2, 4 and 
8. 
 
 
Change from baseline in Body Surface Area (BSA) at Week 2, 4 and 8. 
 
 
Number of treatment-emergent adverse events (TEAEs) in each treatment group. 
 
3.3 Exploratory Endpoints 
 
 
Change from baseline in Trans epidermal water loss (TEWL) at week 2, 4 and 8 (selected sites 
only). 


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 
Plasma total and free DGLA concentrations at Baseline, weeks 4 and 8. 
 
 
Plasma total fatty acid profile at Baseline, week 4 and week 8 (sample to be retained and analyzed 
at a later date). 
 
 
Interleukin profile at Baseline, week 4 and week 8 (Sample to be retained and analyzed at a later 
date) 
4 STUDY DESIGN  
Approximately 100 patients with moderate to severe atopic dermatitis will be included in this multicenter, 
double-blind, placebo controlled, phase IIa study. All subjects will sign an informed consent and undergo 
screening for study eligibility. Subjects will be randomized (1:1) at baseline visit to either receive oral 
DS107G 2 g, or placebo once daily for 8 weeks in a fasting state.  
 
Subjects will come to the clinic on 6 occasions: at screening, baseline, week 2, week 4, week 8 (end of 
treatment/early termination) and week 10 (follow-up). All subjects will exit the study at the Week 10 visit. 
The primary efficacy variable will be the proportion of patients achieving an IGA of 0 (clear) or 1 (almost 
clear) and a decrease of at least 2 points in IGA at week 8. Secondary efficacy variables will include IGA 
at other visits, pruritus (obtained from the SCORAD visual analog scale), EASI, BSA, POEM, DLQI, 
SCORAD and TEWL (for selected sites only). Safety will be assessed through adverse events, physical 
examination, vital signs and safety laboratory tests (including pregnancy tests for women of childbearing 
potential). Pharmacokinetic samples will be obtained at Baseline (Day 0), week 4 and week 8 visits in order 
to measure total and free DGLA plasma trough levels.  Separate plasma sample will be retained for later 
analysis of total fatty acid profile and interleukin profile 
5 STUDY POPULATION  
Approximately 100 subjects with moderate to severe atopic dermatitis as per IGA score and a BSA of 
minimum 10% may be included in this study. Subjects will be men or women, 18 years or older.  
5.1 Inclusion Criteria 
 
Subjects may be eligible if they meet all the following inclusion criteria at the screening and baseline visits 
unless specified otherwise:  
1. Male or female subject aged 18 years and older on the day of signing the informed consent form 
(ICF). 
 
2. Clinically confirmed diagnosis of active atopic dermatitis according to Hanifin and Rajka criteria 
(Appendix G). 
 
3. Moderate to severe atopic dermatitis at baseline as defined by an IGA of minimum 3 at baseline 
visit. 
 
4. Atopic dermatitis covering minimum 10% of the body surface area at baseline. 
 
5. Body mass index (BMI) is between 18 and 35 kg/m2 inclusively. 
 
6. Female patients of childbearing potential must use adequate contraception or have a sterilized 
partner for the duration of the study: systemic hormonal contraceptives, intrauterine device or 
barrier method of contraception in conjunction with spermicide, or agree to sexual abstinence. 


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Hormonal contraceptives must be on a stable dose for at least one month before baseline. Note: 
Women of non-child bearing potential are;  
 
- 
women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or 
tubal ligation) 
- 
women greater than 60 years of age  
- 
women greater than 40 and less than 60 years of age who have had a cessation of menses 
for at least 12 months and a follicle-stimulating hormone (FSH) test confirming non-
childbearing potential (FSH ≥40 mIU/mL) or cessation of menses for at least 24 months 
without FSH levels confirmed.  
 
7. Patients who are able and willing to stop treatment for atopic dermatitis throughout the study 
(except for allowed emollients; see Section 6.3.1). 
 
8. Capable and willing to give signed informed consent and the consent must be obtained prior to any 
study related procedures. 
 
5.2 Exclusion Criteria 
 
Subjects will not be eligible if they meet any of the following criteria at the screening and baseline visits 
unless specified otherwise:  
1. Female patients with positive pregnancy test at screening or Day 0 visit (baseline) or lactating women. 
2. Any clinically significant controlled or uncontrolled medical condition or laboratory abnormality that 
would, in the opinion of the investigator, put the patient at undue risk or interfere with interpretation of 
study results.  
3. Clinically significant impairment of renal or hepatic function. 
4. Other skin conditions that might interfere with atopic dermatitis diagnosis and/or evaluation (such as 
psoriasis or current viral, bacterial and fungal skin infections). 
5. History of hypersensitivity to any substance in DS107G or placebo capsules. 
6. Use of biologics 3 months prior to start of treatment/ Day 0 visit (baseline), or 5 half-lives (whichever is 
longer). 
7. Use of systemic treatments (other than biologics) that could affect atopic dermatitis less than 4 weeks 
prior to baseline visit (Day 0), e.g. retinoids, calcineurin inhibitors, methotrexate, cyclosporine, 
hydroxycarbamide (hydroxyurea), azathioprine and oral/injectable corticosteroids; Intranasal 
corticosteroids and inhaled corticosteroids for stable medical conditions are allowed. 
8. Treatment with any experimental drug within 30 days prior to Day 0 visit (baseline), or 5 half-lives 
(whichever is longer). 
9. Excessive sun exposure, use of tanning booths or other ultraviolet (UV) light sources 4 weeks prior to 
Day 0 visit (baseline) and/or is planning a trip to sunny climate or to use tanning booths or other UV 
sources between screening and follow-up visits. 
10. Use of any topical medicated treatment for atopic dermatitis 2 weeks prior to start of treatment/Day 0 
visit (baseline), including but not limited to, topical corticosteroids, calcineurin inhibitors, tars, bleach, 
antimicrobials and bleach baths. 
 
11. Use of topical products containing urea, ceramides or hyaluronic acid 2 weeks prior to Day 0. 
 
12. Use of anti-histamines for atopic dermatitis within 2 weeks of baseline.  


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13. Significant uncontrolled cardiovascular (a history of ECG abnormalities that are clinically significant in 
the opinion of the investigator), neurologic, malignant, psychiatric, respiratory or hypertensive disease, 
as well as diabetes and arthritis. 
14. Medical history of chronic infectious disease (e.g., hepatitis B, hepatitis C or infection with human 
immunodeficiency virus). 
15. History of clinically significant drug or alcohol abuse in the last year prior to Day 0 (baseline). 
 
5.3 Study Restrictions 
 
Each subject will be questioned on the specific points listed below prior to drug administration. If a subject 
admits a non-compliance with these restrictions, the Principal Investigator (or designee) and/or the sponsor 
will decide whether or not the subject will be permitted to remain in the study. Non-compliance with these 
restrictions will be recorded. 
 
 
Subjects will be instructed to abstain from planning a trip to sunny climate or use of tanning 
equipment between screening and follow-up visits. 
 
 
Subjects will be instructed to abstain from using any drugs/treatments that may influence atopic 
dermatitis (refer to exclusion criteria and prohibited therapies or procedures section) throughout 
the study.  
 
 
Subjects will be required to start fasting at least 8 hours before drug administration upon 
waking. Fasting will continue for at least 60 minutes following drug administration, after which 
subject can have breakfast. Water will be allowed at all times during the fasting period, but no 
other fluids will be permitted. Medication(s) for other conditions that are permitted in the study 
can be taken as usual. 
 
 
For Baseline (Day 0), week 4 and week 8 visits, a blood draw will be performed for PK analysis. 
PK samples must be taken pre-dose; therefore, study drug administration will occur during the 
visit for Day 0 and week 4 visits. Because dosing will occur at the clinic on Day 0 and week 4, 
subjects will be required to fast for at least 8 hours prior to study drug administration and will 
be allowed to have a meal 60 minutes after study drug administration. 
 
5.4 
Discontinuations 
 
Subjects have the right to withdraw from the study at any time for any reason without penalty. The 
investigator also has the right to withdraw subjects from the study if he feels it is in the best interest of the 
subject or if the subject is uncooperative or non-compliant. It is understood by all concerned that an 
excessive rate of withdrawal can render the study un-interpretable; therefore, unnecessary withdrawal of 
subjects should be avoided. Should a subject decide to withdraw, all efforts will be made to complete and 
report the observations, particularly the follow-up examination, as thoroughly as possible. 
 
The investigator or one of his or her staff members should contact the subject either by telephone or through 
a personal visit to determine as completely as possible the reason for the withdrawal, and record the reason 
in subject’s source document and CRF. A complete final early termination (week 8) evaluation at the time 
of the subject’s withdrawal should be made with an explanation of why the subject is withdrawing from the 
study. If the reason for removal of a subject is an adverse event or an abnormal laboratory test result, the 
principal specific event or test will be recorded. Subjects who discontinue the study before week 8 visit will 
be asked to come for an early termination visit as soon as possible and have the assessments listed at 
week 8 performed. They will also be asked to return two weeks later for the safety assessments listed at 


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week 10. 
 
Reasons for discontinuation include: 
 
The investigator decides that the subject should be withdrawn. If this decision is made because of a 
serious or persistent adverse event, laboratory abnormality, or intercurrent illness, the study drug is to 
be discontinued and appropriate measures are to be taken. The investigator will notify the Sponsor or 
designee immediately. 
 
The subject or attending physician requests that the subject be withdrawn from the study. 
 
The subject for any reason requires treatment with another therapeutic agent that has been 
demonstrated to be effective for treatment of the study indication. In this case, discontinuation from the 
study occurs immediately upon introduction of the new agent. 
 
The subject is lost to follow-up, in this case, a reasonable attempt to contact the subject and ascertain 
his/her status must be made and these attempts must be documented. 
 
Serious protocol violation, including persistent non-compliance.  
 
The Sponsor or Regulatory Authorities, for any reason, stops the study. All subjects will be discontinued 
from the study and notified of the reasons for the discontinuation. 
 
Pregnancy at any time during the study.  
 
Other: the subject may withdraw from the study for any other reason, including withdrawal of consent. 
 


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6 TREATMENT 
6.1 Treatment Administration 
 
Subjects who fulfill all the inclusion and none of the exclusion criteria may be accepted in the study. Each 
subject must read and sign an informed consent form prior to any screening procedures being performed. 
This study involves a comparison of DS107G (2 g) with placebo, administered orally once daily upon waking 
for a total duration of 8 weeks. The last study drug administration should occur on the day preceding week 
8 visit / Early Termination (ET) visit. Subjects will be randomized to one of the two treatment groups in a 
1:1 ratio: 
 
 
Treatment group A: 2 grams DS107G (4 capsules) 
 
 
Treatment group B: 2 grams placebo capsules (4 capsules) 
 
 
Subjects will be required to start fasting at least 8 hours before drug administration upon waking. Fasting 
will continue for at least 60 minutes following drug administration, after which subjects can have breakfast. 
Water will be allowed at all times during the fasting period, but no other fluids will be permitted. Medication(s) 
for other conditions that are permitted in the study can be taken as usual. 
 
Blister packs will consist of 7 rows of 4 capsules. Each row constitutes one daily dose. Subjects will be 
instructed to take the 4 capsules from left to right, top to bottom, as shown below: 
 
 
 


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6.2 Study Treatment 
6.2.1 Description 
 
DS107G capsules will be provided by Dignity Sciences as opaque, oval soft gelatin capsules containing 
500mg of DGLA free fatty acid (FFA). 
 
Placebo capsules will be also provided by Dignity Sciences as opaque, oval soft gelatin capsules containing 
500mg of liquid paraffin. 
 
DS107G capsules will be supplied in manufactured form (blinded), packaged in aluminum foil blisters of 28 
units. Placebo will be presented in identical blisters and packs and stored/packaged the same as DS107G 
capsules. Study medication will be labelled according to US and Canadian regulations. 
6.2.2 Storage Conditions 
 
The study medication will be provided by the sponsor to the investigator and will be kept, on site, in a locked 
room or cabinet with limited access. DS107G and placebo capsules should be stored at a controlled room 
temperature between 15-30°C and will only be supplied to subjects in the trial under the supervision of the 
investigator. 
6.2.3 Study Drug Dispensing and Return 
 
Study drug will be dispensed by the study site to the subject at each study visit. Subjects are to return all 
study drug blister packs (used and unused) to the study site. The capsules within blister packs will be 
counted prior to dispensing and upon return and the counts will be recorded in the source documents and 
eCRF. Each subject is to be instructed on the importance of returning study drug at the next study visit. If 
a subject does not return study drug, he/she will be instructed to return it as soon as possible.  
6.2.4 Drug Accountability 
 
The investigator is responsible for maintaining accurate records of the study medication received initially, 
the study drug dispensed/used, the returned medication by subjects and the medication destroyed or 
returned to the Sponsor or designee. All study drug accountability forms and treatment logs must be 
retained in the Investigator’s study file. These records must be available for inspection by the Sponsor, its 
designees or by regulatory agencies at any time. 
 
Used drug boxes/blister packs will be stored safely until destruction and must be accounted for by the 
investigator. The study monitor will perform drug accountability for all study drug at the site and assist in 
returning study drug, including used and unused study drug to the Sponsor or designee. After verification 
of the drug accountability by the sponsor, the investigator will ensure proper destruction or return of the 
remaining study product.  
 
Any study medication accidentally or deliberately destroyed will be accounted for. Any discrepancies 
between amounts dispensed and returned will be explained. 
 
Drug inventory and accountability records will be maintained at each site as per GCP/ICH guidelines.  


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6.2.5 Method of Assignment to Treatment 
 
Approximately 100 patients will be randomized into double-blind treatment groups in a 1:1 ratio by an 
Interactive Web Response System (IWRS) or Interactive Voice Response System (IVRS), as follows: 
 
 
Treatment group A: 2 grams DS107G (4 capsules)  
 
 
Treatment group B: 2 grams placebo capsules (4 capsules)  
 
  
A randomization list permuted blocks and stratified by site will be generated by Dignity Sciences or its 
designee. The randomization schedule with study drug assignments will be generated prior to the start of 
the study and will be known only to the individuals responsible for labeling the study drug. The IVRS or 
IWRS will assign a study drug kit number to each subject and the contents will be based on the 
randomization code.  
 
At the investigational site, each subject will be assigned a patient identifier number during screening that 
will be used on all patient documentation. The patient identifier number will contain the site number and the 
patient number assigned in numerical order at the screening visit (e.g.: 02-010 for the tenth patient screened 
at the site #02). Numbers will be assigned in ascending order starting with 001. 
 
6.2.6 Rationale for Selection and Timing of Doses in the Study 
 
Doses up to 4 g have been well tolerated in healthy subjects. The dose of 2 g has been selected as the 
tested dose in the current study based primarily on the pharmacokinetic results from the Phase I trial which 
suggested saturable skin levels of total DGLA with repeated oral dosing of greater than 2g per day.  
 
In addition the following factors were considered:  
(a) there were less frequent transient gastrointestinal instances recorded at a dose of 2g compared to 
4g daily 
(b) the number of capsules (4) administered daily. A higher dose would be possible but is deemed less 
desirable as too many capsules may have a negative impact on patient adherence to treatment. 
6.2.7 Breaking of Study Blinding 
 
At all times, treatment and randomization information will be kept confidential and will not be released to 
the investigator, the study staff, the CRO or the sponsor’s study team until following the conclusion of the 
study. 
 
Blinding codes should only be broken in emergency situations for reasons of subject safety. The method 
will be either a manual or electronic process. When the blind for a subject has been broken, the reason 
must be fully documented. Whenever possible, the investigator should contact the Sponsor or its designee 
before breaking the blind. If the blind is broken, the investigator should promptly inform the Medical Monitor. 
Documentation of breaking the blind should be recorded with the date and time the blind was broken, and 
the names of the personnel involved. 
 
The subject for whom the blind has been broken will be discontinued from the study and undergo the early 
termination (ET) procedures listed at the Week 8 visit. They will be also asked to return two weeks after the 
early termination visit for the safety assessments listed at Week 10. In cases where there are ethical 
reasons to have the subject remain in the study, the investigator must obtain specific approval from the 
Sponsor or its designee for the subject to continue in the study. 


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6.3 Concomitant Therapy 
 
All medications (including over-the-counter drugs, vitamins, and antacids) taken ≤4 weeks prior to screening 
and throughout the study must be recorded. All medications taken for atopic dermatitis in the 2 months prior 
to screening must be recorded. 
 
Medication entries should be specific to the generic name. Trade name may be used for combination drugs. 
Entries will include the dose, unit, and frequency of administration, route of administration, start date, 
discontinuation date, and indication. If the medication is discontinued, or the dosage changed, these details 
must be recorded. 
 
The Investigator should assess any concomitant procedures, medications, and dietary supplements for 
acceptability that are not explicitly prohibited. 
6.3.1 Permitted therapies 
 
6.3.1.1 Emollients 
 
Subjects can apply a bland emollient of their choice on their skin, including AD lesions, provided that 
emollient use is initiated at least 2 weeks prior to Day 0 and continues at the same frequency and on the 
same skin areas throughout the study. Subjects will be requested to avoid using emollients containing any 
active ingredient which has or may have an effect on atopic dermatitis including the following ingredients: 
 
 
Urea 
 
Ceramide 
 
Hyaluronic acid 
 
Every effort should be made to keep the same emollient throughout the study. The commercial name of the 
selected emollient(s) will be recorded in the source document and the eCRF. No other products may be 
applied to the lesions during the study. 
 
6.3.1.2 Other permitted therapies 
 
 
Non-sedative anti-histamines (e.g. loratadine, fexofenadine) are allowed during the study only if used to 
treat medical conditions other than atopic dermatitis. Such medications are allowed during the study only if 
the subject has been on a stable dose for at least 2 weeks prior to Day 0 and continues to use the same 
agent everyday throughout the study 
 
Inhaled and intranasal corticosteroids for stable medical conditions are allowed.  


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6.3.2 Prohibited therapies or procedures 
 
The following topical therapies or procedures are prohibited during the study for all subjects: 
 
 
Topical medicated treatments that could affect atopic dermatitis, including but not limited to: 
o 
topical corticosteroids 
o 
calcineurin inhibitors 
o 
tars 
o 
bleach 
o 
antimicrobials 
o 
bleach baths 
 
 
Any topical product containing urea, ceramides or hyaluronic acid 
 
Systemic therapy that could affect atopic dermatitis, e.g. retinoids, calcineurin inhibitors, 
methotrexate, cyclosporine, hydroxycarbamide (hydroxyurea), azathioprine and oral/injectable 
corticosteroids  
 
Anti-histamines (except non-sedative anti-histamine) 
 
Any biological agent  
 
UVA or UVB phototherapy 
 
Psoralen + Ultraviolet A (PUVA) therapy  
 
Excessive sun exposure or use of tanning booth 
 
Any investigational agent 
6.3.3 Assessment of Compliance 
 
Treatment compliance will be assessed at each visit by direct questioning, review of the subject’s 
compliance log and capsule count, and will be based on the latter. Subjects will be given a paper diary at 
each visit along with study medication. Subjects will indicate any missed doses on the diary, as well as the 
timing of the last food ingestion prior to study drug administration and food ingestion following study drug 
administration. Subjects will be instructed to bring all capsules and blister packs (used and unused) and 
compliance log to the next study visit. Any deviation from the prescribed dosage regimen will be recorded 
in the source document and in the eCRF. Subjects who are significantly noncompliant will be counseled.  


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7 STUDY PROCEDURES 
Please refer to Appendix A for a flowchart of procedures to perform at each visit. 
7.1 Screening, Visit 1 (Day -30 to -1) 
 
Screening evaluation will only be performed after the subject has agreed to participate and has signed and 
dated the informed consent form. No treatment or trial related procedures will be initiated before the 
informed consent is signed. Day 0 visit must be performed, at the latest, 30 days after the screening visit. 
 
Screening evaluation will be performed according to inclusion and exclusion criteria. If the subject fulfils all 
inclusion criteria and no exclusion criteria, the subject may be included in the study.  
 
The following procedures will be performed at the screening visit: 
 
- 
Informed consent 
- 
Review of Inclusion-Exclusion criteria, including review of Hanifin and Rajka criteria (Appendix G) 
- 
Assign subject identifier number (Site number – Subject number) 
- 
Demographics 
- 
Concomitant medications 
- 
Medical/ surgical history  
- 
Physical examination 
- 
Vital signs  
- 
BMI 
- 
Safety labs (chemistry, coagulation, hematology and urinalysis)  
- 
Serum pregnancy test (women of childbearing potential only) and FSH level test for women greater 
than 40 and less than 60 years of age who have had a cessation of menses for at least 12 months 
but less than 24 months 
- 
BSA evaluation 
- 
IGA 
 
7.2 Baseline, Visit 2 (Day 0) 
 
Subjects are required to fast for at least 8 hours prior to study drug administration. They will be allowed to 
have a meal 60 minutes after study drug administration. 
 
The following procedures will be performed at this visit: 
 
- 
Confirm eligibility with inclusion and exclusion criteria 
- 
Update or confirm medical/surgical history  
- 
Concomitant medications 
- 
Vital signs  
- 
BMI 
- 
Safety labs and biomarkers of inflammation (chemistry, coagulation, hematology, urinalysis, and 
interleukin profile).  
- 
Urine pregnancy test (women of childbearing potential only) 
- 
Pre-dose blood draw pharmacokinetics 
- 
Blood draw total fatty acid profile 
- 
BSA evaluation 
- 
IGA 
- 
EASI assessment 
- 
SCORAD assessment (including VAS pruritus assessment) 
- 
POEM questionnaire  


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- 
DLQI questionnaire 
- 
TEWL assessment (for selected sites only) 
- 
Randomize subject in IVRS/IWRS 
- 
Study drug administration 
- 
Dispensing of study drug  
- 
Dispensing of Subject Compliance Log 
- 
Adverse events evaluation (after first study drug administration)  
 
7.3 Week 2, Visit 3 (Day 14 ± 2 days) 
 
The following procedures will be performed at this visit: 
 
- 
Vital signs 
- 
Urine pregnancy test (women of childbearing potential only) 
- 
BSA evaluation 
- 
IGA 
- 
EASI assessment 
- 
SCORAD assessment (including VAS pruritus assessment) 
- 
POEM questionnaire  
- 
DLQI questionnaire 
- 
TEWL assessment (for selected sites only) 
- 
Collection and dispensing of study drug Review, collection and dispensing of Subject Compliance 
log  
- 
Capsule count  
- 
Concomitant medications 
- 
Adverse events evaluation 
 
7.4 Week 4, Visit 4 (Day 28 ± 2 days) 
 
Subjects are required to fast for at least 8 hours prior to study drug administration. They will be allowed to 
have a meal 60 minutes after study drug administration. 
 
The following procedures will be performed at this visit: 
 
- 
Vital signs 
- 
Urine pregnancy test (women of childbearing potential only) 
- 
Physical examination 
- 
Safety labs and biomarkers of inflammation (chemistry, coagulation, hematology, urinalysis, and 
interleukin profile).  
- 
Pre-dose blood draw pharmacokinetics (if study medication was taken prior to the visit, subject 
must come back the next day) 
- 
Blood draw total fatty acid profile 
- 
BSA evaluation 
- 
IGA 
- 
EASI assessment 
- 
SCORAD assessment (including VAS pruritus assessment) 
- 
POEM questionnaire  
- 
DLQI questionnaire 
- 
TEWL assessment (for selected sites only) 
- 
Study drug administration (instruct subject that last dose should occur on the day preceding week 8 
visit) 
- 
Collection and dispensing of study drug 


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- 
Review, collection and dispensing of Subject Compliance log  
- 
Capsule count  
- 
Concomitant medications 
- 
Adverse events evaluation 
 
7.5 Week 8, Visit 5 (Day 56 ± 2 days) (End of Treatment/Early 
Termination Visit) 
 
The following procedures will be performed at this visit: 
 
- 
Ongoing medical history review 
- 
Vital signs 
- 
Physical examination 
- 
BMI 
- 
Safety labs and biomarkers of inflammation (chemistry, coagulation, hematology, urinalysis and 
interleukin profile).  
- 
Serum pregnancy test (women of childbearing potential only) 
- 
Blood draw pharmacokinetics (if study medication was taken prior to the visit, subject must come 
back the next day) 
- 
Blood draw total fatty acid profile 
- 
BSA evaluation 
- 
IGA 
- 
EASI assessment 
- 
SCORAD assessment (including VAS pruritus assessment) 
- 
POEM questionnaire  
- 
DLQI questionnaire 
- 
TEWL assessment (for selected sites only) 
- 
Collection of study drug 
- 
Review and collection of Subject Compliance log  
- 
Capsule count  
- 
Concomitant medications 
- 
Adverse events evaluation 
 
7.6 Follow-up/Week 10, Visit 6 (Day 70 ± 3 days)  
 
The following procedures will be performed at this visit: 
 
- 
Ongoing medical history review 
- 
Vital signs 
- 
Physical examination 
- 
Safety labs (chemistry, coagulation, hematology and urinalysis): only if clinically significant change 
from baseline in safety lab results at week 8. Urine pregnancy test (women of childbearing potential 
only) 
- 
BSA evaluation 
- 
IGA 
- 
EASI assessment 
- 
SCORAD assessment (including VAS pruritus assessment) 
- 
POEM questionnaire  
- 
DLQI questionnaire 
- 
TEWL assessment (for selected sites only) 
- 
Concomitant medications 
- 
Adverse events evaluation 


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7.7 Early termination visit 
 
In the case the subject ends the study before completion, the procedures listed at Week 8 visit should be 
completed (section 7.5). Subject will also return two weeks later for the following Follow-up/Week 10 
safety assessments: 
 
- 
Concomitant medications 
- 
Safety labs (only if there was a clinically significant change from baseline at the ET visit) 
- 
Urine pregnancy test, if female of childbearing potential 
- 
Vital signs  
- 
Physical exam  
- 
Adverse events 
8 STUDY ASSESSMENTS 
8.1 Efficacy Assessments 
 
Clinical evaluations of atopic dermatitis will be performed by an experienced and qualified dermatologist 
(board certified or equivalent). To assure consistency and reduce variability, the same assessor should 
perform all assessments on a given subject whenever possible.  
 
8.1.1 Investigator’s Global Assessment (IGA) 
 
The Investigator’s Global Assessment (IGA) of Disease Severity (Appendix B) (25, 26) will be assessed at 
each visit. The IGA is a global assessment of the current state of the disease. It is a 6-point morphological 
assessment of overall disease severity and will be determined according to the following definitions: 
0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), 4 (severe) and 5 (very severe). In order to be eligible, 
subjects must have an IGA score >/= 3 at Baseline visit (Day 0).  
 
8.1.2 Eczema Area and Severity Index (EASI) 
 
The Eczema Area and Severity Index (EASI) will be assessed at each visit, except screening visit. It 
quantifies the severity of a subject’s atopic dermatitis based on both lesion severity and the percent of BSA 
affected (24). The EASI is a composite score ranging from 0-72 that takes into account the degree of 
erythema, induration/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for 
each of four body regions, with adjustment for the percent of BSA involved for each body region and for the 
proportion of the body region to the whole body. A detailed procedure of EASI score calculation is provided 
in Appendix C. 
8.1.3 Body Surface Area (BSA) 
 
The overall BSA affected by AD will be evaluated (from 0 to 100%) at each visit. One patient’s palm 
represents 1% of his/her total BSA. For all study visits except at screening, the BSA of involved skin will be 
measured with the SCORAD measurement (see below for description) and evaluated as a separate 
endpoint. In order to be eligible, subjects must have a BSA of at least 10% at Baseline visit (Day 0). 
8.1.4 SCORing Atopic Dermatitis (SCORAD) 
 


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SCORAD will be measured at each visit, except the screening visit. The SCORAD grading system was 
developed by the European Task Force on Atopic Dermatitis (1993) and has been a standard tool to assess 
the AD severity in clinical studies in Europe (27, 28). Six items (erythema, edema/papulation, oozing/crusts, 
excoriation, lichenification, and dryness) will be selected to evaluate the AD severity. The overall BSA 
affected by AD will be evaluated (from 0 to 100%) and included in the SCORAD scores. Loss of sleep and 
pruritus will be evaluated by patients on a visual analog scale (0-10). The sum of these measures represents 
the SCORAD which can vary from 0 to 103. The detailed procedure of SCORAD score calculation is 
provided in Appendix D. 
 
8.1.5 Visual Analog Scale of Pruritus 
 
For all study visits except screening, the pruritus severity score will be recorded with the SCORAD 
measurement and this will be evaluated as a separate endpoint. This will be evaluated by asking subjects 
to indicate on the 10-cm scale (0-10) of the assessment form the point corresponding to the average value 
for the last three days/nights. 
 
8.1.6  Patient-Oriented Eczema Measure (POEM) 
 
The Patient-Oriented Eczema Measure (POEM) will be assessed at each visit, except screening visit. The 
POEM developed by Charman et.al. (29, 30) is a self-assessment of disease severity by the patient. POEM 
has a maximum value of twenty eight based on the patient’s response to seven questions scored according 
to the following scale: 
 
- 
No Days = 0 
- 
1-2 Days = 1 
- 
3-4 Days = 2 
- 
5-6 Days = 3 
- 
Everyday = 4 
 
A detailed description of the POEM assessment is provided in Appendix E. 
8.1.7 Dermatology Quality of Life (DLQI) Questionnaire 
 
The DLQI is a simple 10-question validated questionnaire which will be completed at each visit, except 
screening. The questionnaire is provided in Appendix F. 
 
8.1.8 Transepidermal Water Loss (TEWL) (at selected sites only) 
 
The clinical severity of AD and associated effect on skin barrier function will be evaluated at each visit, 
except the screening visit. This evaluation will be performed at selected sites that have demonstrated 
previous experience with this device. 
 
At Baseline (Day 0), the investigator will select three representative areas of active AD for each subject; 
the location of these sites will be recorded. At subsequent visits, TEWL readings for each area of AD will 
be taken in standard room ambient conditions (22-25˚C, 40-60% relative humidity); the mean of the TEWL 
measurements will be used for the analyses. 


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8.2 Safety Assessments 
8.2.1 Vital Signs 
 
The following vital signs will be recorded at every visit in a seated position, after having sat calmly for at 
least 5 minutes: systolic and diastolic blood pressure (mmHg), pulse (bpm), body temperature (°C) and 
respiratory rate (breath/min).  
 
Weight (kg) and Height (cm) will be collected to calculate the BMI, and will be recorded at the Screening, 
Baseline and week 8 visits. The height will only be recorded once at the screening visit and the same value 
will be used for BMI calculation at baseline and Week 8 visits. 
 
Any abnormal finding related to vital signs that the investigator considers to be clinically significant, must 
be recorded as an AE. 
 
8.2.2 Physical Examination 
 
The following sites/systems will be included in the physical examination. Each system will be scored as 
normal/abnormal (non-clinically significant or clinically significant). Pertinent details must be recorded for 
any clinically significant findings.  
 
General appearance 
 
Dermatological (except Atopic dermatitis) 
 
Head, Eyes, Ears, Nose, Throat (HEENT) 
 
Respiratory 
 
Cardiovascular 
 
Abdominal 
 
Neurological 
 
Musculoskeletal 
 
Lymphatic  
  
8.2.3 Clinical Laboratory Tests 
 
Laboratory tests will be performed at screening, Day 0, Week 4 and Week 8. If Week 8 results indicate a 
clinically significant change from baseline, laboratory tests will also be performed at Week 10. The tests will 
include urinalysis, hematology with differential and coagulation testing, a standard chemistry panel 
(chemistry includes liver function tests and cholesterol), coagulation, serum pregnancy test (screening and 
week 8 / Early termination visits) for women of childbearing potential (WOCBP). At baseline (Day 0), week 
2, week 4 and week 10 visits, a urine pregnancy test will be performed for women of childbearing potential 
(conducted at the investigator site). At screening visit, FSH levels will be tested for women greater than 40 
and less than 60 years of age who have had a cessation of menses for at least 12 months but less than 24 
months. The specific tests in these panels are listed below: 
 
 


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Table 1 Clinical Laboratory Testing 
 
Laboratory testing 
Tests included 
Hematology 
Basophils, Eosinophils, HCT, HGB, Lymphocytes, MCH, MCV, Monocytes, 
Neutrophils, platelets, RBC, WBC 
Coagulation panel 
(frozen) 
APTT, INR, PT 
Serum Chemistry 
Albumin, Alkaline Phosphatase, ALT, AST, Chloride, Cholesterol (non-fasting), CK, 
Creatinine (Enzymatic), GGT, Glucose Random, LDH, Potassium, Sodium, Total 
Bilirubin, Triglycerides, Urea (BUN), Uric Acid 
β-hCG for females of childbearing potential (Screening and week 8 / Early 
termination) 
Urinalysis 
Blood, Glucose, pH, Protein 
Laboratory Tests 
Required at Screening 
only 
FSH levels for women greater than 40 and less than 60 years of age who have had a 
cessation of menses for at least 12 months but less than 24 months. 
8.2.4 Total and Free DGLA plasma levels, Total Fatty Acid Profile and 
Interleukins levels 
 
At Baseline, week 4 and week 8 visits, blood draws will be performed prior to study drug administration 
(no study drug administration at week 8 visit). If a subject comes to the clinic after taking their daily dose of 
study medication, this subject will be required to come back the following day for PK blood draws. Total 
DGLA and free DGLA trough plasma levels will be measured. A second blood draw will be performed for 
later evaluation of total fatty acid profile in plasma. The blood draw for serum chemistry analysis will be split 
in two aliquots for chemistry analysis and later evaluation of interleukins. 
 
The date and time of the subject’s last dose at home before the visit will be recorded accurately. The study 
site will instruct subjects not to take their daily study drug dose at home for week 4 visit. Dosing will occur 
in the clinic during the study visit. The exact time of the sample collection must be recorded. 
 
Blood samples will be processed as soon as possible, no later than 1 hour after blood collection. The 
plasma obtained will be transferred in polypropylene tubes. Each tube will be labeled in order to identify the 
analyte to be assayed. All samples will be frozen in an upright position. The detailed instruction for PK, 
Total Fatty Acid and interleukin sample collection, processing, storage and shipment will be provided in the 
central laboratory manual. The labels on each tube will include at least the following information: 
 
- 
Study protocol 
- 
Site number 
- 
Subject identification number 
- 
Visit name 
- 
Analyte name  
- 
Primary (A) or Duplicate (B) 
 
Shipment of the experimental samples will be shipped to ICON Central Laboratories. 
 


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Detailed instructions for shipment will be provided in the central laboratory manual. Samples will then be 
shipped to the analytical facility and will be analyzed using a validated analytical method in compliance with 
their standard operating procedures.  
 
Blood specimens for PK analysis will be maintained in a blinded fashion. 
9 ADVERSE EVENTS  
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, 
without regard to the possibility of a causal relationship with this treatment.  
 
Investigators are responsible for monitoring the safety of subjects who are participating in this study and for 
alerting the Sponsor of any event that seems unusual, even if this event may be considered an 
unanticipated benefit to the subject. The investigator is responsible for appropriate medical care of subjects 
during the study. 
 
The investigator remains responsible for following through an appropriate health care option, adverse 
events that are serious or that caused the subject to discontinue before completing the study. The subject 
should be followed until the event is resolved or stable. Follow-up frequency is left to the discretion of the 
investigator. 
 
Safety will be evaluated by collecting adverse events, vital signs, performing physical examinations and 
evaluating laboratory results. The reported adverse events will be coded according to MedDRA terminology. 
 
Prior to enrollment, study site personnel will note the occurrence and nature of each subject’s medical 
condition(s) in the appropriate section of the source document and CRF. During the study, site personnel 
will again note any change in the condition(s) and the occurrence and nature of any adverse events.  
 
If a subject experiences an adverse event after the first dose of the study drug, the event will be recorded 
as an adverse event in the source document and CRF. All AEs will be described in the source documents 
and in the CRF. 
 
9.1.1 Adverse Events Causality 
 
The investigator will establish causality of the AE to experimental treatment. The investigator should take 
into account the subject’s history, most recent physical examination findings, and concomitant medications.  
 
The following definitions will be used to determine causality of an AE:  
 
- 
Not related: temporal relationship of the onset of the AE, relative to the experimental treatment is 
not reasonable or another cause can explain the occurrence of the AE. 
 
- 
Related: temporal relationship of the onset of the AE, relative to the experimental treatment is 
reasonable, follows a known response pattern to the treatment, and an alternative cause is unlikely. 
9.1.2 Adverse Events Severity 
 
The intensity of an AE is an estimate of the relative severity of the event made by the investigator based 
on his or her clinical experience and familiarity with the literature. The following definitions are to be used 
to rate the severity of an AE: 
 


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- 
Mild: The symptom is barely noticeable to the subject and does not influence performance of daily 
activities. Treatment is not ordinarily indicated. 
 
- 
Moderate: The symptom is sufficiently severe to make the subject uncomfortable, and performance 
of daily activities is influenced. Treatment may be necessary. 
 
- 
Severe: The symptom causes severe discomfort, and daily activities are significantly impaired or 
prevented. Treatment may be necessary. 
9.1.3 Serious Adverse Events 
 
If a patient experiences a serious adverse event after the first dose of the study drug, the event will be 
recorded as a serious adverse event. All AEs will be described in the source documents and in the CRF. 
A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose: 
 
results in death, 
 
is life-threatening, 
 
requires in-subject hospitalization or prolongation of existing hospitalization, 
 
results in persistent or significant disability/incapacity, or 
 
is a congenital anomaly/birth defect. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the subject 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 were more severe. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate 
in other situations, such as important medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the 
other outcomes listed in the definition above. These should also usually be considered serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or development of drug 
dependency or drug abuse. 
9.1.4 SAE Reporting: 
 
Any Serious Adverse Event, related or not, occurring during the study must be reported on a SAE Form 
within 24 hours of awareness to the CRO: 
 
Innovaderm Research 
Fax   (514) 221-4199 
If a fax is not available within 24 hours of awareness: 
Email: efaxcro@innovaderm.ca 
   
 


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The SAE will be reported by the CRO to the following Sponsor’s Representative Product Life Limited: 
 
Name: James Wilson    
Title: Pharmacovigilance Associate 
Company name: Product Life Limited 
Tel. (+44 1223) 402660 (Working hours) 
Tel. (+44 1223) 402660 (nights, weekends, and holidays) JAM answering service is in operation for all calls 
outside working hours. 
Fax. (+44 1223 413689) 
Email: safety@productlife-group.com 
 
 
Product Life will process and evaluate all SAEs as soon as the reports are received and will assess the 
expectedness of each SAE to the study treatment. For each SAE received, Product Life will make a 
determination as to whether the criteria for expedited reporting to relevant regulatory authorities have been 
met. Product Life will manage the expedited reporting of relevant safety information to concerned regulatory 
agencies in accordance with local laws and regulations. 
9.2 Pregnancy Reporting 
 
If a subject becomes pregnant during the study, the subject should inform the study site as soon as possible. 
Upon confirmation of the pregnancy, the subject must be withdrawn from study drug but may continue study 
participation. The Investigator must complete a study-specific Pregnancy Form upon confirmation of a 
pregnancy and send it to Innovaderm Research within 24 hours of confirmation of the pregnancy. 
Innovaderm Research will report all cases of pregnancy to the Sponsor in a timely manner (contact 
information to be used are the same as for SAE reporting). Post-treatment follow-up should be done to 
ensure subject safety. Pregnancy is not itself an AE or SAE; however, maternal/fetal complications or 
abnormalities will be recorded as AEs or SAEs, as appropriate. The investigator will follow the pregnancy 
until completion (or until pregnancy termination) and notify Innovaderm Research of the outcome as a follow 
up to the initial Pregnancy Form. 
10 DATA QUALITY ASSURANCE/SITE MONITORNG 
During the study, monitoring visits will be conducted at regular intervals. The monitoring visits will be 
conducted to ensure protocol adherence, quality of data, accuracy of entries in the eCRF, drug 
accountability, compliance with regulatory requirements and continued adequacy of the investigational site 
and its facilities.  
 
The site may be audited and/or monitored by a quality assurance officer named by the Sponsor and/or 
regulatory authorities may wish to perform on-site audits. The investigator will be given notice before an 
audit occurs and will be expected to cooperate with any audit, provide assistance and documentation 
(including source data) as requested. 
11 DATA COLLECTION AND RETENTION 
Subject data will be entered by site personnel using Medrio eClinical Overnight, a web based electronic 
data capture (EDC) and reporting system. This application will be set up for remote entry. Medrio Inc. are 
the developers and owners of Medrio eClinical Overnight. The EDC software has been fully validated and 
conforms to 21 CFR Part 11 requirements. Investigator site staff will not be given access to the EDC system 
until they have been fully trained by the Sponsor or delegate. Designated investigator staff will enter the 
data required by the protocol into the eCRFs using this web based application. Automatic validation 
programs check for data discrepancies in the eCRFs and, by generating appropriate error messages, allow 


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modification or verification of the entered data by the investigator staff before confirming the data. The 
investigator must certify that the data are complete and accurate by applying an electronic signature to the 
eCRFs.  
 
The investigator must maintain source documents for each subject in the study, consisting of case and visit 
notes (clinical medical records) containing demographic and medical information and the results for any 
tests or assessments. All information on the eCRFs must be traceable to these source documents in the 
subject’s file. Data not requiring a written or electronic record will be defined before study start and will be 
recorded directly on the eCRFs, which will be documented as being the source data. 
 
The data collected will be encoded and stored electronically in a database system. Validated data may 
subsequently be transferred to the sponsor. 
12 CONFIDENTIALITY OF TRIAL DOCUMENTS AND SUBJECT 
RECORDS  
The investigator must assure that the subjects’ anonymity will be maintained and that their identities are 
protected from unauthorized parties. On CRFs or other document submitted to the Sponsor, subjects should 
not be identified by their names, but by an identification code. The Investigator should keep a subject 
enrolment log relating codes with the names of subjects. The Investigator should maintain documents not 
for submission to the sponsor e.g., subjects’ written consent forms, in the strictest confidence. 
13 INVESTIGATOR’S FILES/RETENTION OF DOCUMENTS 
The Investigator must maintain adequate and accurate records to enable the conduct of the study to be 
fully documented and the study data to be subsequently verified. These records include, but are not limited 
to, the identity of all participating subjects, all original signed informed consent documents, copies of all 
CRFs, safety reporting forms, source documents, and detailed records of treatment disposition, and 
adequate documentation of relevant correspondence. These documents should be classified into two 
different separate categories: Investigator Study File and Subject Clinical Source Documents. 
The records should be retained by the investigator according to International Conference on Harmonisation 
(ICH), local regulations, or as specified in the Clinical Trial Agreement (CTA), whichever is longer.  


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14 SAMPLE SIZE AND STATISTICAL METHODS  
14.1 Determination of Sample Size 
 
 
 
The primary endpoint can be translated as a responder analysis where a subject will be classified as 
Responder if he/she achieves an IGA score of 0 (clear) or 1 (almost clear) at Week 8, considering a 2-point 
decrease from baseline. A sample size of 45 subjects will have a power of 80% to detect a statistically 
significant difference of 25% between responders from treated group and from the placebo group, based 
on a chi-square test and an alpha of 0.05. Based on the literature review, it is expected that the placebo 
could reach up to 7%, so the minimal proportion expected in the treated group should be at least 32%. 
Allowing for 10% drop-out, a total of 100 subjects should be enrolled in the study. 
14.2 Statistical and Analytical Plans 
 
Continuous variables will be summarized in tables and will include the number of subjects, mean, standard 
deviation, median, minimum, maximum and inter-quartile range. Categorical variables will be presented in 
tables as frequencies and percentages.  
 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, unless otherwise 
specified. 
14.2.1 Subject Disposition 
 
Efficacy will be evaluated on the basis of the ITT population and analyses will be performed based on the 
randomized treatment and not on the treatment received. 
 
The per-protocol (PP) population will include all subjects who were randomized with no significant protocol 
deviations. The specific criteria for the PP population and the ITT population will be detailed in a separate 
statistical analysis plan. 
 
The safety population will be defined as all subjects who received at least one dose of the medication. 
Analysis will be done according to the actual treatment they received. 
14.2.2 Efficacy analysis 
 
The primary endpoint can be translated as a responder analysis where a subject will be classified as 
Responder if he/she achieves an IGA score of 0 (clear) or 1 (almost clear) at Week 8, considering a 2-point 
decrease from baseline. The comparison between groups for the primary endpoint will be done using a 
Cochran-Mantel–Haenszel test with site included as a stratification factor. A supportive analysis will be 
performed using a Fisher’s exact test. The primary efficacy analysis will be done using observed values 
and a supportive analysis will be conducted using the last observation carried forward (LOCF) approach. 
The analyses will be done using the ITT population and will serve as the primary analysis while the analysis 
of the primary endpoint using the PP population will be used a sensitivity analysis. 
 
The secondary endpoints involving change from baseline will be analyzed using an analysis-of-covariance 
(ANCOVA) including the change from baseline as the dependent, the site and treatment group and site as 
fixed effects, and the baseline value as covariate. Ls-means and 95% CI will be presented along with 
corresponding p-value from the comparison of treatment. The secondary endpoints involving proportion will 
be analyzed using a Cochran-Mantel-Haenszel test stratified by site and p-value will be presented. 


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Analyses for the secondary endpoints will be done using observed data and no imputation will be used for 
missing observation.  
 
 
All details regarding the statistical analyses will be included in a separate statistical analysis plan. 
14.2.3 Safety Analysis 
 
All adverse events (AEs) that occur after the first study drug administration during the study will be classified 
on the basis of Medical Dictionary for Regulatory Activities (MedDRA) terminology. Descriptions of AEs will 
include the date of onset, the date the AE ended (if it resolved), the severity and seriousness of the AE, the 
relationship of the AE to study medication, and the outcome. The focus in this protocol will be limited to 
treatment emergent adverse events. 
 
Reported AEs will be summarized by the number of subjects reporting the events, as well as by System 
Organ Class, Preferred Term, severity, seriousness, and relationship to study medication. For the summary 
of AEs by severity, each patient will be counted only once within a System Organ Class or a Preferred Term 
by using the AEs with the highest intensity within each category for each analysis. For the summary of AEs 
by relationship to study medication, each patient will be counted only once within a System Organ Class or 
a Preferred Term by using the AEs with the greatest reported relationship within each category. For the 
summary of AEs by relationship to study medication and severity, each patient will be counted only once 
within a System Organ Class or a Preferred Term by using (1) the greatest reported relationship followed 
by (2) the highest reported intensity. 
 
All information pertaining to AEs noted during the study will be listed by patient, detailing verbatim, System 
Organ Class, Preferred Term, start date, stop date, intensity, outcome and relationship to study drug. The 
AE onset will also be shown relative (in number of days) to the day of test article administration. Serious 
adverse events (SAEs) will be tabulated by treatment group, relationship to the test article, and a reference 
to the occurrence of the SAEs to the relative day of dosing. 
 
Concomitant medications will be coded with the WHO-Drug Dictionary and listed by subject. 
 
In addition, a list of subjects who discontinued from the study and a list of subjects who experienced SAEs 
will also be provided. 
 
Results from laboratory analyses and vital signs will be tabulated using descriptive statistics. The value at 
visit as well as the change from baseline will be presented descriptively. 
 
No inferential statistics will be done on safety variables (TEAEs, concomitant medication, laboratory and 
vital signs). 
15 ETHICS 
15.1 Local Regulations/Declaration of Helsinki 
 
This study will be conducted in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki (2008) and that are consistent with “Good Clinical Practice” ICH Tripartite Guideline (July 2002) 
and the applicable laws and regulations of the country in which the research is conducted, whichever affords 
the greater protection to the individual.  


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15.2 Ethical Review  
 
It is the understanding of the Sponsor that this protocol (and any amendment) as well as appropriate 
consent procedures, will be reviewed and approved by a research ethics board/institutional review board 
(REB/IRB). This Board must operate in accordance with the current Federal regulations. A letter or 
certification of approval will be sent by the Investigator to the Sponsor prior to initiation of the study, and 
also whenever subsequent modifications to the protocol are made.  
15.3 Informed Consent  
 
It is the responsibility of the Investigator, or a person designated by the Investigator (if acceptable by local 
regulation), to obtain written informed consent from each individual participating in this study after adequate 
explanation of the aims, methods, objectives and potential hazards of the study. It must also be explained 
to the subjects that they are completely free to refuse to enter the study or to withdraw from it at any time 
for any reason.  
 
If new safety information results in significant changes in the risk/benefit assessment or any new information 
that may affect willingness to continue to participate, the consent form should if necessary be reviewed and 
updated by the Research Ethics Board/Institutional Review Board. All subjects (including those already 
being treated) should be informed of the new information, given a copy of the revised form and asked to 
give their consent to continue in the study. 
 
 
16 PUBLICATION POLICY  
Sponsor permission is required for publication but is reflective of applicable laws and regulation. The 
Publication Policy will be addressed in the Research and Financial agreement, and all details outlined in 
the agreement will apply to this protocol.  
 
17 REFERENCES 
 
1. 
Williams HC. Atopic eczema. BMJ. 1995 Nov 11;311(7015):1241-2. 
2. 
De Benedetto A, Agnihothri R, McGirt LY, Bankova LG, Beck LA. Atopic dermatitis: a disease 
caused by innate immune defects? J Invest Dermatol. 2009 Jan;129(1):14-30. 
3. 
Williams HC. Clinical practice. Atopic dermatitis. N Engl J Med. 2005 Jun 2;352(22):2314-24. 
4. 
Leung DY, Bieber T. Atopic dermatitis. Lancet. 2003 Jan 11;361(9352):151-60. 
5. 
Silverberg JI. Persistence of childhood eczema into adulthood. JAMA Dermatol. 2014 Jun 
1;150(6):591-2. 
6. 
Bos JD, Kapsenberg ML, Smitt JH. Pathogenesis of atopic eczema. Lancet. 1994 May 
28;343(8909):1338-41. 
7. 
Homey B, Steinhoff M, Ruzicka T, Leung DY. Cytokines and chemokines orchestrate atopic skin 
inflammation. J Allergy Clin Immunol. 2006 Jul;118(1):178-89. 
8. 
Wolter S, Price HN. Atopic dermatitis. Pediatr Clin North Am. 2014 Apr;61(2):241-60. 
9. 
Arkwright PD, Motala C, Subramanian H, Spergel J, Schneider LC, Wollenberg A. Management of 
difficult-to-treat atopic dermatitis. J Allergy Clin Immunol Pract. 2013 Mar;1(2):142-51. 
10. 
USDA National Nutrient Database for Standard Reference, Release 26, Software v.1.4, 2014 
[database on the Internet]. Available from: http://ndb.nal.usda.gov/. 
11. 
Scollan ND, Choi NJ, Kurt E, Fisher AV, Enser M, Wood JD. Manipulating the fatty acid composition 
of muscle and adipose tissue in beef cattle. Br J Nutr. 2001 Jan;85(1):115-24. 
12. 
Makrides M, Simmer K, Neumann M, Gibson R. Changes in the polyunsaturated fatty acids of 
breast milk from mothers of full-term infants over 30 wk of lactation. Am J Clin Nutr. 1995 Jun;61(6):1231-
3. 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 40 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
13. 
Kawashima H, Toyoda-Ono Y, Suwa Y, Kiso Y. Subchronic (13-week) oral toxicity study of dihomo-
gamma-linolenic acid (DGLA) oil in rats. Food Chem Toxicol. 2009 Jun;47(6):1280-6. 
14. 
Teraoka N, Kawashima H, Shiraishi-Tateishi A, Tanaka T, Nakamura J, Kakutani S, et al. Oral 
supplementation with dihomo-gamma-linolenic acid-enriched oil altered serum fatty acids in healthy men. 
Biosci Biotechnol Biochem. 2009 Jun;73(6):1453-5. 
15. 
Tanaka T, Kakutani S, Horikawa C, Kawashima H, Kiso Y. Oral supplementation with dihomo-
gamma-linolenic acid (DGLA)-enriched oil increases serum DGLA content in healthy adults. Lipids. 2014 
Jun;47(6):643-6. 
16. 
Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, et al. Dietary 
supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy 
humans. J Nutr. 1997 Aug;127(8):1435-44. 
17. 
Laidlaw M, Holub BJ. Effects of supplementation with fish oil-derived n-3 fatty acids and gamma-
linolenic acid on circulating plasma lipids and fatty acid profiles in women. Am J Clin Nutr. 2003 
Jan;77(1):37-42. 
18. 
Lovell CR, Burton JL, Horrobin DF. Treatment of atopic eczema with evening primrose oil. Lancet. 
1981 Jan 31;1(8214):278. 
19. 
Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet. 1982 Nov 
20;2(8308):1120-2. 
20. 
Fiocchi A, Sala M, Signoroni P, Banderali G, Agostoni C, Riva E. The efficacy and safety of gamma-
linolenic acid in the treatment of infantile atopic dermatitis. J Int Med Res. 1994 Jan-Feb;22(1):24-32. 
21. 
Ziboh VA, Miller CC, Cho Y. Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: 
generation of antiinflammatory and antiproliferative metabolites. Am J Clin Nutr. 2000 Jan;71(1 
Suppl):361S-6S. 
22. 
Miller CC, Ziboh VA. Gammalinolenic acid-enriched diet alters cutaneous eicosanoids. Biochem 
Biophys Res Commun. 1988 Aug 15;154(3):967-74. 
23. 
Kawashima H, Tateishi N, Shiraishi A, Teraoka N, Tanaka T, Tanaka A, et al. Oral administration 
of dihomo-gamma-linolenic acid prevents development of atopic dermatitis in NC/Nga mice. Lipids. 2008 
Jan;43(1):37-43. 
24. 
Tofte S, Graeber M, Cherill R, Omoto M, Thurston M, Hanifin JM. Posters - P48 - Eczema area and 
severity index (EASI): A new tool to evaluate atopic dermatitis. [abstract]. J Eur Acad Dermatol Venereol. 
1998;11(suppl 2):S197. 
25. 
Hanifin JM. Atopic dermatitis. J Am Acad Dermatol. 1982 Jan;6(1):1-13. 
26. 
Rajka G, Langeland T. Grading of the severity of atopic dermatitis. Acta Derm Venereol Suppl 
(Stockh). 1989;144:13-4. 
27. 
Rullo VE, Segato A, Kirsh A, Sole D. Severity scoring of atopic dermatitis: a comparison of two 
scoring systems. Allergol Immunopathol (Madr). 2008 Jul-Aug;36(4):205-11. 
28. 
Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task 
Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31. 
29. 
Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and 
initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Arch 
Dermatol. 2004 Dec;140(12):1513-9. 
30. 
The patient-oriented eczema measure: development and initial validation of a new tool for 
measuring atopic eczema severity from the patients' perspective - correction. Arch Dermatol. 2005 
Dec;141(3):381. 
31. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl. 
1980;92:44-7. 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 41 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
18 APPENDIX A 
 Study Flow Chart 
Visit 
Screening 
Baseline 
Week 2 
Week 4 
Week 8 / 
ET visit 
Follow up 
visit / Week 
10 
Day 
-30 to -1 
0 
14 (± 2) 
28 (± 2) 
56 (± 2) 
70 (±3) 
Informed Consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical / Surgical History 
X 
X 
 
 
 
 
Ongoing medical historyƔ 
 
 
 
 
X 
X 
Review Inclusion/Exclusion Criteria  
X 
X 
 
 
 
 
Hanifin and Rajka criteria 
X 
 
 
 
 
 
Assign subject identifier number 
X 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Safety labs and inflammation 
biomarkers: Serum Chemistry 
(including FSH levels at screening 
when applicable¥ and interleukin 
profile), Coagulation, Hematology, 
urinalysis  
X Φ 
X 
 
X 
X 
(X**) Φ,  
Pharmacokinetics (pre-dose blood 
draw)††  
 
X 
 
X 
X 
 
Blood draw for fatty acid profile 
sample††,  
 
X 
 
X 
X 
 
Pregnancy Test (-hCG if female of 
childbearing potential)* 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
X 
X 
X 
BMI 
X 
X 
 
 
X 
 
Study Drug Administration (on site)€ 
 
X 
 
X 
§ 
 
Dispense Study Drug 
 
X 
X 
X 
 
 
Collect Study Drug 
 
 
X 
X 
X 
 
Dispense Subject Compliance Log 
 
X 
X 
X 
 
 
Collect and Review Subject 
Compliance Log 
 
 
X 
X 
X 
 
Capsule count 
 
 
X 
X 
X 
 
BSA 
X 
X 
X 
X 
X 
X 
IGA 
X 
X 
X 
X 
X 
X 
EASI assessment 
 
X 
X 
X 
X 
X 
SCORAD assessment / VAS 
pruritus assessment 
 
X 
X 
X 
X 
X 
POEM questionnaire 
 
X 
X 
X 
X 
X 
DLQI questionnaire 
 
X 
X 
X 
X 
X 
TEWL (selected sites only) 
 
X 
X 
X 
X 
X 
Adverse Events† 
 
X† 
X 
X 
X 
X 
¥:: For women greater than 40 and less than 60 years of age who have had a cessation of menses for at least 12 months but less 
than 24 months 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 42 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
**: Only if clinically significant change from baseline in safety lab results at week 8 
*: Serum pregnancy test at screening and week 8 / ET visits, urine test pregnancy for all other visits 
††: If a subject took study medication prior to the visit, he/she will be required to come back the following day for PK blood draws. 
€: Subjects must be fasting for at least 8 hours before and 60 minutes after drug administration 
§: Subjects will be instructed to take their last study drug dose the day preceding week 8 visit. 
†: Collection of AE will start after the first study drug administration 
Ɣ: Assessment if any ongoing condition has improved since baseline. 
Φ: Interleukin profile will not be evaluated at screening and week 10. 
 In the case the subject ends the study before completion, the subject will also return 2 weeks after the ET visit for safety 
assessments listed at Week 10. 

 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 43 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
19 APPENDIX B – INVESTIGATOR’S GLOBAL ASSESSMENT  
 
Score 
Grade 
Definition 
0 
Clear 
No evidence of disease with the exception of residual pigment changes 
and/or xerosis 
1 
Almost clear 
Perceptible erythema, papulation/infiltration 
2 
Mild 
Mild erythema, papulation/infiltration 
3 
Moderate 
Moderate erythema, papulation/infiltration 
4 
Severe 
Severe erythema, papulation/infiltration 
5 
Very Severe 
Severe erythema, papulation/infiltration with oozing/crusting 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 44 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
20 APPENDIX C - Eczema Area and Severity Index (EASI) 
 
Four anatomic sites – head, upper extremities, trunk and lower extremities – are assessed for erythema, 
induration (papules), excoriation and lichenification as seen on the day of the examination. The severity of 
each sign is assessed using a 4-point scale: 
 
• 
0 = No symptoms 
• 
1 = Slight 
• 
2 = Moderate 
• 
3 = Marked 
 
The area affected by atopic dermatitis within a given anatomic site is estimated as a percentage of the total 
area of that anatomic site and assigned a numerical value according to the degree of atopic dermatitis 
involvement as follows: 
 
• 
0 = no involvement 
• 
1 = < 10 % 
• 
2 = 10 to < 30% 
• 
3 = 30 to < 50% 
• 
4 = 50 to < 70% 
• 
5 = 70 to < 90% 
• 
6 = 90 to 100 % 
 
The EASI score is obtained by using the formula 
 
EASI = 0.1 (Eh + Ih + Exh + Lh) Ah + 0.2 (Eu + Iu + Exu + Exu) Au + 0.3 (Et 
+ It + Ext + Ext) At + 0.4 (El + Il + Exl + Exl) Al 
 
Where E, I, Ex, L and A denote erythema, induration, excoriation, lichenification and area, respectively, and 
h, u, t, and l denote head, upper extremities, trunk, and lower extremities, respectively. 
 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 45 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
21 APPENDIX D - SCORing Atopic Dermatitis (SCORAD) 
Six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) are 
selected to evaluate the AD severity. The intensity of each item is graded using a 4-point scale: 
 
• 
0 = No symptoms 
• 
1 = Mild 
• 
2 = Moderate 
• 
3 = Severe 
 
The area chosen for grading must be representative (average intensity) for each item. The individual 
intensity ratings for each item will then be added (ranging from 0-18) and multiplied by 3.5, giving a maximal 
score of 63. 
 
The overall BSA affected by AD is evaluated (from 0 to 100%) and divided by 5. One patient’s palm 
represents 1% of his/her total BSA. The maximum is 20. 
 
Subjective items include loss of sleep and the occurrence of pruritus. These are evaluated by asking 
patients to indicate on the 10-cm scale (0-10) of the assessment form the point corresponding to the 
average value for the last three days/nights. The combined maximum score of these two is 20. 
 
The sum of the above measures represents the SCORAD which can vary from 0 to 103. If the subjective 
scores of pruritus and loss of sleep are excluded, the SCORAD becomes objective SCORAD (score range 
0-83) 
 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 46 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
22 APPENDIX E - Patient-Oriented Eczema Measure (POEM) 
 
Patient ID #: ___ ___ - ___ ___ ___  
 
Patient Initials: ___ ___ ___ 
 
Visit Day: ___________ 
 
Visit Date (dd-mmm-yyyy):______________ 
 
Please circle one response for each of the seven questions below about your eczema. Please 
leave blank any questions you feel unable to answer. 
 
1. Over the last week, on how many days has your skin been itchy because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
2. Over the last week, on how many nights has your sleep been disturbed because of your 
eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
3. Over the last week, on how many days has your skin been bleeding because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
4. Over the last week, on how many days has your skin been weeping or oozing clear fluid 
because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
5. Over the last week, on how many days has your skin been cracked because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
6. Over the last week, on how many days has your skin been flaking off because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
7. Over the last week, on how many days has your skin felt dry or rough because of your eczema? 
 
No days 
1-2 days 
3-4 days 
5-6 days 
Every day 
 
 
 
 
© CR Charman, AJ Venn, HC Williams, December 2004. 
 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 47 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
23 APPENDIX F – Dermatology Life Quality Index (DLQI) 
 
Patient ID #: ___ ___ - ___ ___ ___  
 
Patient Initials: ___ ___ ___ 
 
Visit Day: ___________ 
 
Visit Date (dd-mmm-yyyy):______________ 
The aim of this questionnaire is to measure how much your skin problem has affected 
your life OVER THE LAST WEEK. Please check one box for each question. 
 
1. Over the last week, how itchy, sore, painful or stinging 
has your skin been? 
Very 
much 
A lot 
A little 
Not at all 

 
 
 
2. Over the last week, how embarrassed or self conscious 
have you been because of your skin? 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
3. Over the last week, how much has your skin interfered 
with you going shopping or looking after your home or 
yard? 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
4. Over the last week, how much has your skin influenced 
the clothes you wear? 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
5. Over the last week, how much has your skin affected any 
social or leisure activities? 
 
 
 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
6. Over the last week, how much has your skin made it 
difficult for you to do any sport? 
 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 48 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
7. Over the last week, has your skin prevented you from 
working or studying? 
yes 
no 
 

 
 
Not relevant 
 
If "No", over the last week how much has your skin been a 
problem at work or studying? 
A lot 
A little 
Not at all  
 
 
 
 
 
 
 
8. Over the last week, how much has your  
skin created 
problems with your partner or any of your close friends or 
relatives?   
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
9. Over the last week, how much has your  
skin caused 
any sexual difficulties?  
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
10 Over the last week, how much of a problem has the 
treatment for your skin been, for example by making your 
home messy, or by taking up time? 
Very 
much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant 
 
©AY Finlay, GK Khan, April 1992 www.dermatology.org.uk. 
 
Please check you have answered EVERY question. Thank you. 
 


Protocol DS107G-02 – ORAL DS107 IN MODERATE TO SEVERE ATOPIC DERMATITIS 
Page 49 of 49 
Protocol version 2.2: 22 July 2015 
 
Confidential and property. Permission should be obtained before any reproduction. 
24 APPENDIX G - Diagnostic Criteria for Atopic Dermatitis 
 
Per Inclusion Criterion 2, a subject is to have a clinical diagnosis of atopic dermatitis according to the 
criteria of Hanifin and Rajka (31). The criteria go as follows: 
 
 
Major Criteria (must have at least three) 
Pruritus 
Typical morphology and distribution: 
Adults: flexural lichenification or linearity 
Children and infants: involvement of facial and extensor surfaces 
Chronic or relapsing dermatitis 
Personal or family history of atopy 
 
 
Minor Criteria (must have at least three) 
Xerosis 
Icthyosis/keratosis pilaris/palmer hyperlinearity 
Immediate (type 1) skin test reactivity 
Elevated serum IgE 
Early age at onset 
Tendency to skin infections (Staphylococcus aureus, herpes simplex)/impaired cellular 
immunity 
Hand/foot dermatitis 
Nipple eczema 
Conjunctivitis 
Dennie-Morgan fold 
Keratoconus 
Anterior subcapsular cataracts 
Orbital darkening 
Facial pallor/erythema 
Pityriasis alba 
Anterior neck folds 
Itch when sweating 
Intolerance to wool and lipid solvents 
Perifollicular accentuation 
Food intolerance 
Course influenced by environmental/emotional factors 
White demographic/delayed blanch 
 

SAP_001.pdf: 
 
 
Protocol number: 
DS107G-02 
 
A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE II STUDY 
TO ASSESS THE EFFICACY AND SAFETY OF ORALLY ADMINISTERED DS107G 
TO PATIENTS WITH MODERATE TO SEVERE ATOPIC DERMATITIS 
Statistical Analysis Plan 
FINAL 
Prepared by Josée Morin 
Effective date: 
19 OCT 2015 
 
Version 1.0 
 


 
SAP version FINAL 1.0: DS107G-02 
19 OCT 2015 
Page 2 of 107 
 
 
SIGNATURE PAGE 
 
Prepared by:  
Josée Morin 
 
 
 
 
Senior Biostatistician 
Excelsus Statistics 
Date  
 
Signature 
 
Approved by: 
Annie Lévesque 
 
 
 
 
Director, Scientific Affairs  
Innovaderm Research Inc. 
Date  
 
Signature 
 
Approved by: 
Blánaid Ní Chuinneagáin 
 
 
 
 
Clinical Scientist 
Dignity Sciences 
Date  
 
Signature 
 
 
 
 


 
SAP version FINAL 1.0: DS107G-02 
19 OCT 2015 
Page 3 of 107 
 
Statistical Analysis Plan 
TABLE OF CONTENTS 
 
SIGNATURE PAGE ................................................................................................... 2 
TABLE OF CONTENTS ............................................................................................. 3 
LIST OF ABBREVIATIONS ......................................................................................... 5 
1 
Introduction ........................................................................................................ 7 
2 
Study Objectives ................................................................................................. 7 
3 
Study Methods ................................................................................................... 7 
3.1 
General Study Design and Plan ..................................................................... 7 
3.2 
Inclusion-Exclusion Criteria and General Study Population ............................... 10 
3.2.1 
Inclusion Criteria ....................................................................................... 10 
3.2.2 
Exclusion Criteria ...................................................................................... 11 
3.3 
Randomization and Blinding ........................................................................ 12 
3.4 
Study Variables .......................................................................................... 12 
3.4.1 
Demographics and Baseline Characteristics .................................................. 12 
3.4.2 
Efficacy Variables ...................................................................................... 13 
3.4.3 
Safety Variables ........................................................................................ 18 
4 
Sample Size ..................................................................................................... 20 
5 
General Considerations ..................................................................................... 20 
5.1 
Timing of Analyses ..................................................................................... 20 
5.2 
Analysis Populations ................................................................................... 20 
5.2.1 
Intent-to-treat Population ............................................................................ 20 
5.2.2 
Safety Population ...................................................................................... 20 
5.2.3 
Per-Protocol Population ............................................................................. 21 
5.3 
Missing Data/Multiple Observations .............................................................. 21 


 
SAP version FINAL 1.0: DS107G-02 
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Page 4 of 107 
 
5.4 
Multi-centre Studies .................................................................................... 21 
5.5 
Multiple Testing .......................................................................................... 22 
6 
Summary of Study Data ..................................................................................... 22 
6.1 
Subject Disposition ..................................................................................... 22 
6.2 
Protocol Deviations .................................................................................... 23 
6.3 
Demographic and Baseline Variables ............................................................ 23 
6.4 
Medical History .......................................................................................... 23 
6.5 
Prior and Concomitant Medications............................................................... 23 
6.6 
Exposure and Treatment Compliance ........................................................... 23 
7 
Efficacy Analyses .............................................................................................. 24 
7.1 
Primary Efficacy Analysis ............................................................................ 24 
7.2 
Secondary Efficacy Analyses ....................................................................... 24 
7.3 
Exploratory Efficacy Analyses ...................................................................... 25 
8 
Safety Analyses ................................................................................................ 25 
9 
Reporting Conventions ...................................................................................... 27 
10 
Technical Details ........................................................................................... 27 
11 
Summary of Changes to the Protocol................................................................ 27 
12 
References ................................................................................................... 27 
13 
Mock Tables, Listings and Figures ................................................................... 28 
13.1 
Mock Tables .............................................................................................. 28 
13.2 
Mock Listings ............................................................................................. 66 
13.3 
Mock Figures ............................................................................................. 99 
 
 
 


 
SAP version FINAL 1.0: DS107G-02 
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Page 5 of 107 
 
LIST OF ABBREVIATIONS 
 
AD 
Atopic Dermatitis 
AE 
Adverse Event/Adverse Experience 
ANCOVA 
Analysis of Covariance 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
CI 
Confidence Interval 
CRF 
Case Report Form 
CS 
Clinically Significant 
DGLA 
Dihomo-gamma-linolenic acid 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
ICF 
Informed Consent Form 
IGE 
Investigator’s Global Evaluation of Eczema  
ITT 
Intent-to-treat 
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web Response System 
LOCF 
Last Observation Carried Forward 
LLN 
Lower Limit of Normal 
LLT 
Lower Level Term 
MedDRA © 
Medical Dictionary for Regulatory Activities 
NCS 
Non-clinically significant 
POEM 
Patient Oriented Eczema Measure 
PP 
Per Protocol 
PT 
Preferred Term 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SAF 
Safety Population 
SAP 
Statistical analysis plan 
SCORAD 
SCORing of Atopic Dermatitis 
SD 
Standard Deviation 


 
SAP version FINAL 1.0: DS107G-02 
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Page 6 of 107 
 
SOC 
System Organ Classification 
TEAE 
Treatment-Emergent Adverse Event/Adverse Experience 
TEWL 
Trans Epithelial Water Loss 
ULN 
Upper Limit of Normal 
WHODD 
World Health Organisation Drug Dictionnary 
VAS 
Visual Analog Scale 
 
 
 


 
SAP version FINAL 1.0: DS107G-02 
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Page 7 of 107 
 
1 Introduction 
All statistical analyses will be performed in accordance with the protocol DS107G-02, dated 22-
JUL-2015 (Version 2.2). This statistical analysis plan (SAP) includes a comprehensive and 
detailed description of the statistical methods and presentation of the data analysis by adding 
more details to the proposed methods in the protocol. The purpose of the SAP is to define the 
statistical approaches for the analysis of study data prior to database lock. 
2 Study Objectives 
Primary objectives: To compare the efficacy of orally administered DS107G capsules versus 
placebo, in the treatment of adult patients with moderate to severe atopic dermatitis. 
Secondary objective: To assess the safety of orally administered DS107G capsules versus 
placebo, in adult patients with moderate to severe atopic dermatitis. 
3 Study Methods 
3.1 General Study Design and Plan 
Approximately 100 patients with moderate to severe atopic dermatitis will be included in this 
multicenter, double-blind, placebo controlled, phase IIa study. All subjects will sign an informed 
consent and undergo screening for study eligibility. Subjects will be randomized (1:1) at baseline 
visit to either receive oral DS107G 2 g, or placebo once daily for 8 weeks in a fasting state.  
Subjects will come to the clinic on 6 occasions: at screening, baseline, week 2, week 4, week 8 
(end of treatment/early termination) and week 10 (follow-up). All subjects will exit the study at the 
Week 10 visit. The primary efficacy variable will be the proportion of patients achieving an IGA of 
0 (clear) or 1 (almost clear) and a decrease of at least 2 points in IGA at week 8. Secondary 
efficacy variables will include IGA at other visits, pruritus (obtained from the SCORAD visual 
analog scale), EASI, BSA, POEM, DLQI, SCORAD and TEWL (for selected sites only). Safety 
will be assessed through adverse events, physical examination, vital signs and safety laboratory 
tests (including pregnancy tests for women of childbearing potential). Pharmacokinetic samples 
will be obtained at Baseline (Day 0), week 4 and week 8 visits in order to measure total and free 
DGLA plasma trough levels. A separate plasma sample will be retained for later analysis of total 
fatty acid profile and interleukin profile. 
The study flow chart of all assessment and timing is presented in Figure 1. 
 
 
 


 
SAP version FINAL 1.0: DS107G-02 
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Page 8 of 107 
 
Figure 1. Study Flow Chart 
Visit 
Screening 
Baseline 
Week 2 
Week 4 
Week 8 / 
ET visit 
Follow up 
visit / Week 
10 
Day 
-30 to -1 
0 
14 (± 2) 
28 (± 2) 
56 (± 2) 
70 (±3) 
Informed Consent 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical / Surgical History 
X 
X 
 
 
 
 
Ongoing medical historyƔ 
 
 
 
 
X 
X 
Review Inclusion/Exclusion Criteria  
X 
X 
 
 
 
 
Hanifin and Rajka criteria 
X 
 
 
 
 
 
Assign subject identifier number 
X 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Safety labs and inflammation 
biomarkers: Serum Chemistry 
(including FSH levels at screening 
when applicable¥ and interleukin 
profile), Coagulation, Hematology, 
urinalysis  
X Φ 
X 
 
X 
X 
(X**) Φ,  
Pharmacokinetics (pre-dose blood 
draw)††  
 
X 
 
X 
X 
 
Blood draw for fatty acid profile 
sample††,  
 
X 
 
X 
X 
 
Pregnancy Test (-hCG if female of 
childbearing potential)* 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
X 
X 
X 
BMI 
X 
X 
 
 
X 
 
Study Drug Administration (on site)€ 
 
X 
 
X 
§ 
 
Dispense Study Drug 
 
X 
X 
X 
 
 
Collect Study Drug 
 
 
X 
X 
X 
 
Dispense Subject Compliance Log 
 
X 
X 
X 
 
 
Collect and Review Subject 
Compliance Log 
 
 
X 
X 
X 
 
Capsule count 
 
 
X 
X 
X 
 
BSA 
X 
X 
X 
X 
X 
X 
IGA 
X 
X 
X 
X 
X 
X 
EASI assessment 
 
X 
X 
X 
X 
X 
SCORAD assessment / VAS 
pruritus assessment 
 
X 
X 
X 
X 
X 
POEM questionnaire 
 
X 
X 
X 
X 
X 
DLQI questionnaire 
 
X 
X 
X 
X 
X 
TEWL (selected sites only) 
 
X 
X 
X 
X 
X 
Adverse Events† 
 
X† 
X 
X 
X 
X 
¥:: For women greater than 40 and less than 60 years of age who have had a cessation of menses for at least 12 months but less 
than 24 months 
**: Only if clinically significant change from baseline in safety lab results at week 8 


 
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*: Serum pregnancy test at screening and week 8 / ET visits, urine test pregnancy for all other visits 
††: If a subject took study medication prior to the visit, he/she will be required to come back the following day for PK blood draws. 
€: Subjects must be fasting for at least 8 hours before and 60 minutes after drug administration 
§: Subjects will be instructed to take their last study drug dose the day preceding week 8 visit. 
†: Collection of AE will start after the first study drug administration 
Ɣ: Assessment if any ongoing condition has improved since baseline. 
Φ: Interleukin profile will not be evaluated at screening and week 10. 
In the case the subject ends the study before completion, the subject will also return 2 weeks after the ET visit for safety 
assessment listed at Week 10. 
 
 


 
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3.2 Inclusion-Exclusion Criteria and General Study Population 
To participate in the study, subjects must meet all the inclusion criteria and none of the exclusion 
criteria. 
3.2.1 Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for this study: 
 
Male or female subject aged 18 years and older on the day of signing the informed 
consent form (ICF). 
 
Clinically confirmed diagnosis of active atopic dermatitis according to Hanifin and 
Rajka criteria. 
 
Moderate to severe atopic dermatitis at baseline as defined by an IGA of minimum 3 
at baseline visit. 
 
Atopic dermatitis covering minimum 10% of the body surface area at baseline. 
 
Body mass index (BMI) is between 18 and 35 kg/m2 inclusively. 
 
Female patients of childbearing potential must use adequate contraception or have a 
sterilized partner for the duration of the study: systemic hormonal contraceptives, 
intrauterine device or barrier method of contraception in conjunction with spermicide, 
or agree to sexual abstinence. Hormonal contraceptives must be on a stable dose for 
at least one month before baseline. Note: Women of non-child bearing potential are: 
- 
women who have had surgical sterilization (hysterectomy or bilateral 
oophorectomy or tubal ligation) 
- 
women greater than 60 years of age  
- 
women greater than 40 and less than 60 years of age who have had a 
cessation of menses for at least 12 months and a follicle-stimulating hormone 
(FSH) test confirming non-childbearing potential (FSH ≥40 mIU/mL) or 
cessation of menses for at least 24 months without FSH levels confirmed. 
 
Patients who are able and willing to stop treatment for atopic dermatitis throughout 
the study (except for allowed emollients). 
 
Capable and willing to give signed informed consent and the consent must be 
obtained prior to any study related procedures. 
 
 


 
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3.2.2 Exclusion Criteria 
Subjects must not have the following to be eligible for this study: 
 
Female patients with positive pregnancy test at screening or Day 0 visit (baseline) 
or lactating women. 
 
Any clinically significant controlled or uncontrolled medical condition or laboratory 
abnormality that would, in the opinion of the investigator, put the patient at undue 
risk or interfere with interpretation of study results.   
 
Clinically significant impairment of renal or hepatic function. 
 
Other skin conditions that might interfere with atopic dermatitis diagnosis and/or 
evaluation (such as psoriasis or current viral, bacterial and fungal skin infections). 
 
History of hypersensitivity to any substance in DS107G or placebo capsules. 
 
Use of biologics 3 months prior to start of treatment/ Day 0 visit (baseline), or 5 half-
lives (whichever is longer). 
 
Use of systemic treatments (other than biologics) that could affect atopic dermatitis 
less than 4 weeks prior to baseline visit (Day 0), e.g. retinoids, calcineurin inhibitors, 
methotrexate, cyclosporine, hydroxycarbamide (hydroxyurea), azathioprine and 
oral/injectable corticosteroids; Intranasal corticosteroids and inhaled corticosteroids 
for stable medical conditions are allowed. 
 
Treatment with any experimental drug within 30 days prior to Day 0 visit (baseline), 
or 5 half lives (whichever is longer). 
 
Excessive sun exposure, use of tanning booths or other ultraviolet (UV) light sources 
4 weeks prior to Day 0 visit (baseline) and/or is planning a trip to sunny climate to 
use tanning booths or other UV sources between screening and follow-up visits. 
 
Use of any topical medicated treatment for atopic dermatitis 2 weeks prior to start of 
treatment/Day 0 visit (baseline), including but not limited to, topical corticosteroids, 
calcineurin inhibitors, tars, bleach, antimicrobials and bleach baths. 
 
Use of topical products containing urea, ceramides or hyaluronic acid for 2 weeks 
prior to Day 0. 
 
Use of anti-histamines for atopic dermatitis within 2 weeks of baseline. 
 
Significant uncontrolled cardiovascular (a history of ECG abnormalities that are 
clinically significant in the opinion of the investigator), neurologic, malignant, 
psychiatric, respiratory or hypertensive disease, as well as diabetes and arthritis. 
 
Medical history of chronic infectious disease (e.g., hepatitis B, hepatitis C or infection 
with human immunodeficiency virus). 
 
History of clinically significant drug or alcohol abuse in the last year prior to Day 0 
(baseline). 
 


 
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3.3 Randomization and Blinding 
Approximately 100 patients will be randomized into double-blind treatment groups a 1:1 ratio by 
an Interactive Web Response System (IWRS) or Interactive Voice Response System (IVRS), as 
follows: 
• Treatment group A: 2 grams DS107G (4 capsules)  
• Treatment group B: 2 grams placebo capsules (4 capsules)  
A randomization list permuted blocks will be generated by Dignity Sciences or its designee. The 
randomization schedule with study drug assignments will be generated prior to the start of the 
study and will be known only to the individuals responsible for labeling the study drug. The IVRS 
or IWRS will assign a study drug kit number to each subject and the contents will be based on 
the randomization code. 
Each subject will be assigned a patient identifier number during screening that will be used on all 
patient documentation. The patient identifier number will contain the site number and the patient 
number assigned in numerical order at the screening visit (e.g.: 02-010 for the tenth patient 
screened at the site #02). Numbers will be assigned in ascending order starting with 001.  
Four patients were randomized under site 6X instead of site 06 (6X-001, 6X-002, 6X-004 and 
6X-005). Those 4 patients will be reassigned to site 06 for the presentation and the 
summarization of the results. 
 
3.4 Study Variables 
3.4.1 Demographics and Baseline Characteristics  
Age calculated in years is defined as the difference between the informed consent date and the 
birthdate. 
Gender is a code list where 1 equals Male and 2 equals Female. 
Height in centimeters measured to the nearest centimeter. 
Weight in kilograms (kg) measured to one decimal place.  
Body Mass Index (BMI) will be calculated as the weight (kg) divided by the square of height (m) 
and rounded to one decimal place (kg/m2). 
Race is an integer ranging from 1 to 6, where 1 corresponds to American Indian or Alaska Native, 
2 corresponds to Asian, 3 corresponds to Black or African American, 4 corresponds to Native 
Hawaiian or Other Pacific Islander, 5 corresponds to White, and 6 corresponds to Other. 
Ethnicity is code list where 1 corresponds to ‘Hispanic or Latino’ and 2 corresponds to ‘Not 
Hispanic or Latino’.    


 
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Medical History 
Medical history will be coded using the Body System Code as the following: Eyes-Ears-Nose-
Throat, 
Respiratory 
(Asthma/Other), 
Cardiovascular, 
Gastrointestinal, 
Hepatobiliary, 
Genitourinary/ Renal, Reproductive, Neurological, Endocrine, Hematological, Musculoskeletal, 
Dermatologic, Extremities, Immunological, Psychiatric, and Allergies. 
 
Medications 
Medications will be coded using the Preferred Term from the WHO Drug Dictionary (Sept-2014 
B2). If the start and end dates of the medication are prior to the study drug start date then the 
medication will be coded as prior medication. Otherwise the medication will be considered as 
concomitant medications. 
 
3.4.2 Efficacy Variables 
3.4.2.1 Primary Efficacy Variable  
The primary efficacy variable is the Investigator’s Global Assessment (IGA) of Disease 
Severity and will be assessed at each visit. The IGA is a global assessment of the current state 
of the disease. It is a 6-point morphological assessment of overall disease severity and will be 
determined according to the following definitions: 
 
Score  
Grade  
Definition 
0 
Clear 
No evidence of disease with the exception of residual pigment 
changes and/or xerosis 
1 
Almost clear 
Perceptible erythema, papulation/infiltration 
2 
Mild 
Mild erythema, papulation/infiltration 
3 
Moderate 
Moderate erythema, papulation/infiltration 
4 
Severe 
Severe erythema, papulation/infiltration 
5 
Very Severe 
Severe erythema, papulation/infiltration with oozing/crusting 
 
Change from Baseline will be calculated as the value at the visit minus the value at Baseline. The 
change will be calculated at Week 2, Week 4, Week 8, and Week 10. Percent change from 
baseline will also be calculated. In addition, change and percent change from Week 8 to Week 
10 will be calculated. 
The IGA will be also examined using the following criteria: 
- 
IGA of 0 (clear) or 1 (almost clear) at Week 8;  
- 
at least a 2-point decrease in IGA at Week 8; 
- 
at least a 1-point decrease in IGA at Week 8; 
- 
No Change or Increased from Baseline in IGA at Week 8 


 
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3.4.2.2 Secondary Efficacy Variable  
Secondary efficacy variables are as follows: 
 
The Eczema Area and Severity Index (EASI) will be assessed at each visit, except 
screening visit. It quantifies the severity of a subject’s atopic dermatitis based on both 
lesion severity and the percent of BSA affected.  
Four anatomic sites – head, upper extremities, trunk, and lower extremities – are assessed 
for erythema, induration (papules), excoriation and lichenification as seen on the day of 
the examination. The severity of each sign is assessed using a 4-point scale: 0 = No 
symptoms, 1 = Slight, 2 = Moderate, 3 = Marked. 
The area affected by atopic dermatitis within a given anatomic site is estimated as a 
percentage of the total area of that anatomic site and assigned a numerical value 
according to the degree of atopic dermatitis involvement as follows: 0 = no involvement, 1 
= < 10 %, 2 = 10 to < 30%, 3 = 30 to < 50%, 4 = 50 to < 70%, 5 = 70 to < 90%, 6 = 90 to 
100 %. 
The EASI score is obtained by using the formula: 
EASI =  0.1 * (Eh + Ih + Exh + Lh) * Ah +  
 
0.2 * (Eu + Iu + Exu + Exu) * Au +  
 
0.3 * (Et + It + Ext + Ext) * At +  
 
0.4 * (El + Il + Exl + Exl) * Al 
Where E, I, Ex, L and A denote erythema, induration, excoriation, lichenification and area, 
respectively, and h, u, t, and l denote head, upper extremities, trunk, and lower extremities, 
respectively. The EASI score ranges from 0 (no disease) - 72 (maximal disease). The 
score will be set to missing in case of at least one missing value.  
The change from baseline in EASI at Week 2, Week 4, Week 8, and Week 10 will be 
calculated as the value at the visit minus the value at Baseline. Percent change from 
baseline will also be calculated. In addition, change and percent change from Week 8 to 
Week 10 will be calculated. 
 
 
The overall Body Surface Area (BSA) affected by AD will be evaluated (from 0 to 100%) 
at each visit. One patient’s palm represents 1% of his/her total BSA. For all study visits 
except at screening, the BSA of involved skin will be measured with the SCORAD 
measurement. The change from Baseline will be calculated as the value at the visit minus 
the value at Baseline. The change from baseline will be calculated at Week 2, Week 4, 
Week 8 and Week 10. Percent change from baseline will also be calculated. In addition, 
change and percent change from Week 8 to Week 10 will be calculated. 
 
 


 
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 
The SCORing Atopic Dermatitis (SCORAD) will be measured at each visit, except the 
screening visit. The SCORAD grading system is a standard tool to assess the AD severity 
in clinical studies in Europe. Six items (erythema, edema/papulation, oozing/crusts, 
excoriation, lichenification, and dryness) are selected to evaluate the AD severity. The 
intensity of each item is graded using a 4-point scale: 0 = No symptoms, 1 = Mild, 2 = 
Moderate, 3 = Severe. 
The area chosen for grading must be representative (average intensity) for each item. The 
individual intensity ratings for each item will then be added (ranging from 0-18) and 
multiplied by 3.5, giving a maximal score of 63. 
The overall BSA affected by AD is evaluated (from 0 to 100%) and divided by 5. One 
patient’s palm represents 1% of his/her total BSA. The maximum is 20. 
Subjective items include loss of sleep and the occurrence of pruritus. These are evaluated 
by asking patients to indicate on the 10-cm scale (0-10) of the assessment form the point 
corresponding to the average value for the last three days/nights. The combined maximum 
score of these two is 20. 
The sum of the above measures represents the SCORAD which can vary from 0 to 103. 
If the subjective scores of pruritus and loss of sleep are excluded, the SCORAD becomes 
objective SCORAD (score range 0-83). 
The score will be set to missing if there is at least one missing value. The change from 
Baseline will be calculated as the value at the visit minus the value at Baseline. The 
change from baseline will be calculated at Week 2, Week 4, Week 8, and Week 10. 
Percent change from baseline will also be calculated. In addition, change and percent 
change from Week 8 to Week 10 will be calculated. 
 
 
The Visual Analog Scale (VAS) of Pruritus will be assessed with the SCORAD 
measurement for all study visits except screening. This will be evaluated by asking 
subjects to indicate on the 10-cm scale (0-10) of the assessment form the point 
corresponding to the average value for the last three days/nights. The change from 
Baseline will be calculated as the value at the visit minus the value at Baseline. The 
change from baseline will be calculated at Week 2, Week 4, Week 8, and Week 10. 
Percent change from baseline will also be calculated. In addition, change and percent 
change from Week 8 to Week 10 will be calculated. 
 
 
The Patient-Oriented Eczema Measure (POEM) will be assessed at each visit, except 
screening visit. The POEM is a self assessment of disease severity by the patient. The 
following questions are to be rated as: 0=No Days, 1=1-2 Days, 2=3-4 Days, 3=5-6 Days, 
4=Everyday. 


 
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1. Over the last week, on how many days has your skin been itchy because of your 
eczema? 
2.  Over the last week, on how many nights has your sleep been disturbed because of 
your eczema? 
3. Over the last week, on how many days has your skin been bleeding because of 
your eczema? 
4. Over the last week, on how many days has your skin been weeping or oozing clear 
fluid because of your eczema? 
5. Over the last week, on how many days has your skin been cracked because of your 
eczema? 
6. Over the last week, on how many days has your skin been flaking off because of 
your eczema? 
7. Over the last week, on how many days has your skin felt dry or rough because of 
your eczema? 
The POEM score is the sum of the 7 question ratings for a possible total of 28 (more 
severe eczema). The score will be set to missing if there is at least one missing value. The 
change from Baseline will be calculated as the value at the visit minus the value at 
Baseline. The change from baseline will be calculated at Week 2, Week 4, Week 8, and 
Week 10. Percent change from baseline will also be calculated. In addition, change and 
percent change from Week 8 to Week 10 will be calculated 
 
 
The Dermatology Life Quality Index (DLQI) questionnaire is a simple 10-question 
validated questionnaire which will be completed at each visit, except screening. The 
following questions are to be assessed by the patient: 
1. Over the last week, how itchy, sore, painful or 
stinging has your skin been? 
Very much (3) 
A lot (2) 
A little (1) 
Not at all (0) 
 
 
 
 
2. Over the last week, how embarrassed or self 
conscious have you been because of your skin? 
Very much (3) 
A lot (2) 
A little (1) 
Not at all (0) 
 
3. Over the last week, how much has your skin 
interfered with you going shopping or looking 
after your home or yard? 
Very much (3) 
A lot (2) 
A little (1) 
Not at all  
 
 
 
Not relevant (0) 
4. Over the last week, how much has your skin 
influenced the clothes you wear? 
Very much (3) 
A lot (2) 
A little (1) 
 
 
 


 
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Not at all 
Not relevant (0) 
5. Over the last week, how much has your skin 
affected any social or leisure activities? 
 
 
 
Very much (3) 
A lot (2) 
A little (1) 
Not at all 
 
 
 
Not relevant (0) 
6. Over the last week, how much has your skin made 
it difficult for you to do any sport? 
 
Very much (3) 
A lot (2) 
A little (1) 
Not at all 
 
 
 
Not relevant (0) 
7. Over the last week, has your skin prevented you 
from working or studying? 
Yes (3) 
No (0) 
 
 
 
If "No", over the last week how much has your skin 
been a problem at work or studying? 
A lot (2) 
A little (1) 
Not at all (0) 
 
8. Over the last week, how much has your skin 
created problems with your partner or any of your 
close friends or relatives?   
Very much (3) 
A lot (2) 
A little (1) 
Not at all 
 
 
 
Not relevant (0) 
9. Over the last week, how much has your skin 
caused any sexual difficulties? 
 
Very much (3) 
A lot (2) 
A little (1) 
Not at all 
 
 
 
Not relevant (0) 
10. Over the last week, how much of a problem has the 
treatment for your skin been, for example by 
making your home messy, or by taking up time? 
Very much (3) 
A lot (2) 
A little (1) 
Not at all 
 
 
 
Not relevant (0) 
 
The DLQI score is the sum of the 10 questions for a possible total of 30 (quality of life is 
impaired). ‘Not relevant” and “Unanswered’ questions will be scored as 0. The change 
from Baseline will be calculated as the value at the visit minus the value at Baseline. The 
change from baseline will be calculated at Week 2, Week 4, Week 8, and Week 10. 
Percent change from baseline will also be calculated. In addition, change and percent 
change from Week 8 to Week 10 will be calculated  
 
 
Trans epidemal Water Loss (TEWL), the clinical severity of AD and associated effect on 
skin barrier function will be evaluated at each visit, except the screening visit. This 
evaluation will be performed at selected sites that have demonstrated previous experience 
with this device. 
At Baseline (Day 0), the investigator will select three representative areas of active AD for 
each subject; the location of these sites will be recorded. At subsequent visits, TEWL 
readings for each area of AD will be taken in standard room ambient conditions (22-25˚C, 
40-60% relative humidity); the mean of the TEWL measurements will be used for the 


 
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analyses. The change from Baseline will be calculated as the value at the visit minus the 
value at Baseline. The change from baseline will be calculated at Week 2, Week 4, Week 
8, and Week 10. Percent change from baseline will also be calculated. In addition, change 
and percent change from Week 8 to Week 10 will be calculated. 
 
3.4.3 Safety Variables  
3.4.3.1 Adverse Events  
Treatment-emergent adverse events (TEAEs) are defined as AEs that developed, worsened or 
became serious after the first dose of study drug during the study, i.e. from the study drug start 
date to the end of study.  
TEAEs will be coded according to Medical Dictionary for Regulatory Activities (MedDRA, version 
17.0) terminology. The coding process using MedDRA will be conducted by the data management 
where lower level term (LLT), the preferred term (PT) and system organ class (SOC) will be 
assigned to each AE term. 
Descriptions of AEs will include the date of onset, the date the AE ended (if it resolved), the 
severity and seriousness of the AE, the relationship of the AE to study medication, and the 
outcome. If the onset date of the AE is incomplete or missing and the end date is incomplete or 
missing, or the end date is after the start of treatment, then the event will be evaluated as a TEAE. 
If the start date is at the Baseline Visit and the end date is incomplete or missing, then the event 
will be evaluated as a TEAE. The AE onset will also be shown relative (in number of days) to the 
day of first dose. 
 


 
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3.4.3.2 Laboratory Safety Variables 
Urinalysis, hematology (with differential and coagulation testing), a standard chemistry panel 
(chemistry includes liver function tests and cholesterol), coagulation, and serum pregnancy test 
for women of childbearing potential will be collected during the study (see Figure 1. Study Flow 
Chart for details). The list of laboratory parameters are presented in Table 1 below. 
 
Table 1. Clinical laboratory Testing 
Laboratory testing 
Tests included 
Hematology 
Basophils, Eosinophils, HCT, HGB, Lymphocytes, MCH, MCV, 
Monocytes, Neutrophils, platelets, RBC, WBC 
Coagulation 
APTT, INR, PT 
Serum Chemistry 
Albumin, Alkaline Phosphatase, ALT, AST, Chloride, Cholesterol 
(non-fasting), CK, Creatinine (Enzymatic), GGT, Glucose Random, 
LDH, Potassium, Sodium, Total Bilirubin, Triglycerides, Urea (BUN), 
Uric Acid 
β-hCG for females of childbearing potential 
Urinalysis 
Blood, Glucose, pH, Protein 
 
Laboratory results will be transferred by the laboratory itself. The data will include the visit date 
and time, the laboratory result type (e.g. hematology), the analyte name, the result, the unit, the 
reference values, and the abnormal flag.  
 
3.4.3.3 Vital Signs 
Vital signs will be assessed at each visit and include systolic and diastolic blood pressure, pulse, 
oral temperature and respiratory rate.  The following variables were created for each vital sign.  
 
Value at the time specified is the value specified for the parameter on the CRF 
 
Change from baseline is the value at the time specified minus the value at baseline 
 
3.4.3.4 Physical Examination 
The following sites/systems will be included in the Physical examination. Each system will be 
scored as: Normal, Abnormal Not Clinically Significant, or abnormal clinically significant. 
- 
General appearance 
- 
Dermatological (except atopic dermatitis) 
- 
Head, Eyes, Ears, Nose, Throat (HEENT) 


 
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- 
Respiratory 
- 
Cardiovascular 
- 
Abdominal 
- 
Neurological 
- 
Musculoskeletal 
- 
Lymphatic 
 
3.4.3.5 Total and Free DGLA plasma levels, Total Fatty Profile and Interleukins levels 
Total DGLA and free DGLA trough plasma levels will be measured at Baseline, week 4 and 
week 8. Total fatty profiles and interleukins levels will not be covered in this SAP. 
4 Sample Size  
The primary endpoint can be translated as a responder analysis where a subject will be classified 
as Responder if he/she achieves an IGA score of 0 (clear) or 1 (almost clear) at Week 8, 
considering a 2-point decrease from baseline. A sample size of 45 subjects will have a power of 
80% to detect a statistically significant difference of 25% between responders from treated group 
and from the placebo group, based on a chi-square test and an alpha of 0.05. Based on the 
literature review, it is expected that the placebo could reach up to 7%, so the minimal proportion 
expected in the treated group should be at least 32%. Allowing for 10% drop-out, a total of 100 
subjects should be enrolled in the study. 
5 General Considerations 
5.1 Timing of Analyses 
The final analysis will be performed on data transferred to the statistician, having been 
documented as meeting the cleaning and approval requirements of the database lock and after 
the finalisation and approval of this SAP document. 
There is no interim analysis planned for this study.  
5.2 Analysis Populations 
5.2.1 Intent-to-treat Population 
The Intent-to-treat (ITT) population will consist of all randomized subjects. Analysis will be done 
according to the randomized treatment. This population will be used for all efficacy analyses. 
 
5.2.2 Safety Population 
The safety population will be defined as all randomized subjects who received at least one dose 
of the medication. Analysis will be done according to the actual treatment subjects received. 
 


 
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5.2.3 Per-Protocol Population 
The per-protocol (PP) population will include all subjects who received at least one dose of the 
medication and who had at least one post-baseline evaluation on the primary endpoint of IGA 
with no significant protocol deviations. Analysis will be done according to the actual treatment 
subjects received. 
 
Protocol deviation will be listed and summarized. Prior to database lock, significant protocol 
deviation will be defined and reviewed in a blinded fashion conjointly by the medical director (or 
delegate) and the statistician. Patients with significant protocol deviations will be excluded from 
the PP population. 
 
The PP population will be used for all efficacy analyses as supportive analyses. 
 
5.3 Missing Data/Multiple Observations 
No imputation will be done for all population and all parameters, except for the primary endpoint. 
A supportive analysis using the last observation carried forward (LOCF) method will be performed 
on responder analysis (see section 7.1 for details). 
In the event that two values were collected for the same visit, the scheduled assessment value 
will be retained in the analyses, unless otherwise specified (e.g. lab error). However, all values 
will be presented in the data listings. Laboratory values of ‘< X’ ou ‘> X’ will be set to ‘X’ for the 
analysis. 
 
5.4 Multi-centre Studies 
The primary efficacy analysis will be performed with site included in the statistical model as a 
stratification factor. A sensitivity analysis will also be conducted without site. Analysis on the 
secondary efficacy endpoints will include information on site. Safety data will be presented with 
all study sites pooled. Safety analysis will be performed with data from all sites being pooled. 
 
To obtain a sufficient and better-balanced number of subjects among study sites, pooling of study 
sites will be applied prior to performing the statistical inference and unblinding treatment. Sites 
without at least 5 subjects in the ITT population will be incorporated into pooled sites as follows: 
 
 
All such sites with less than 5 subjects will be ordered from the lowest to the highest 
in terms of number of ITT subjects. In case of ties, the ordering for tied sites will be 
determined according to the site identification number (from smallest to largest). 
 
Sites will be combined beginning at the smallest until the resulting pooled site 
contains at least 5 ITT subjects. The sites pooled in this way will be considered as 
a single site in the statistical analyses. 
 
The process described above will resume for the remaining sites not meeting the 
criterion of at least 5 subjects. If the final set of pooled site does not meet the criterion 
of at least 5 ITT subjects, the final set will be pooled with the preceding pooled site.  


 
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5.5 Multiple Testing 
Since there are only 2 treatment groups involved in this study, no correction for multiplicity will be 
performed.  
6 Summary of Study Data 
All continuous variables will be summarised using the following descriptive statistics: n (non-
missing sample size), mean, standard deviation (SD), median, inter-quartile range (25th and 
75th percentiles), maximum, and minimum. The frequency and percentages (based on the 
non-missing sample size) of observed levels will be reported for all categorical measures.  
In general, all data will be listed, sorted by treatment group, site and subject, and when appropriate 
by visit number within subject. All summary tables will be structured with a column for each 
treatment in the same order (DS107G, Placebo) and will be annotated with the total population 
size relevant to that table/treatment. 
Day 0 is the first day of study medication. In the event that there is more than one value for a 
given assessment prior to the study drug start date, the value obtained closest to Day 0, before 
administration of study drug will be considered as the baseline value. The baseline value will be 
the value nearest to and before the first dose of the study medication. 
All statistical tests will be two-sided and will be performed with a significant level of 0.05, unless 
otherwise specified. 
 
6.1 Subject Disposition 
Subject disposition information, including the counts and percentages of subjects screened, 
screen failed, randomized, and who completed the study will be summarized based on all enrolled 
subjects (i.e. who signed the informed consent form). 
Tables will be created indicating the number of subjects by treatment group in each of the analysis 
populations and attending each visit. Finally, for each of the analysis populations there will be 
tables indicating by treatment group the number of days in the study, the percentage of subjects 
discontinued and the reasons for discontinuation. Overall comparability of subject’s 
discontinuation between the two treatment groups will be tested using a Fisher exact test and 
overall comparability of the reasons for discontinuation for both treatment groups will be done 
using an exact Pearson’s Chi-Squares test. 
Number of days in the study will be calculated as the difference between the date of the last visit 
(Follow up/Week 10) and the informed consent date plus 1. 
 


 
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6.2 Protocol Deviations 
Protocol deviations may include, but are not limited to: 
• 
Visit outside of the visit window 
• 
Missed visit 
• 
Missed/Extra dose(s) 
• 
Study Procedure(s) not done 
• 
Prohibited medication 
• 
Etc. 
A listing of all protocol deviations will be presented and documented in the study file. A descriptive 
summary table of protocol deviation categories by treatment group will be presented. 
 
6.3 Demographic and Baseline Variables 
Demographic and baseline variables will be analysed using descriptive statistics. 
 
6.4 Medical History 
Medical history will be presented using the frequency and percentage of subject by Body System 
Code. 
6.5 Prior and Concomitant Medications 
Medications will be coded to the preferred generic name using the WHO-Drug dictionary (version 
June 2013 B2). Compound product will be coded to the brand name. Any medications that started 
and ended prior to the study drug start date will be considered as “Prior” and “Concomitant”, 
otherwise. A listing of all medications will be produced. 
 
6.6 Exposure and Treatment Compliance 
Descriptive statistics will be presented by Treatment group on the extent of exposure and the 
compliance. 
 
The extent of exposure will be defined as: 
 
Number of days on drug = Date of Week 8/ET Visit – First dose study drug administration date. 
 
Compliance will be calculated as follows: 
 
(Sum of all capsules dispensed) −(Sum of all capsules returned)
(4 × Number of days on drug)
∗100 
 


 
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7 Efficacy Analyses 
All efficacy variables will be summarized using descriptive statistics by treatment group at 
each visit.  
7.1 Primary Efficacy Analysis 
The primary endpoint can be translated as a responder analysis where a subject will be classified 
as Responder if he/she achieves an IGA score of 0 (clear) or 1 (almost clear) at Week 8, 
considering a 2-point decrease from baseline. Patients who did not complete the study (i.e. 
subjects with an early termination visit at Week 8) will be classified as non-responder.  
The comparison between groups for the primary endpoint will be done using a Cochran-Mantel–
Haenszel (CMH) test where the site will be used as the stratification factor. A sensitivity analysis 
will also be conducted using a Fisher’s exact without Site. Subgroup analyses will also be 
performed on responders vs. non responders (using CMH test stratified for site) for each subgroup 
of patients (Very Severe/Severe and Modreate), separately. 
The primary efficacy analysis will be done using observed values.A supportive analysis will be 
conducted using the LOCF method. For subjects who did not complete the study, the last non-
missing IGA results (including results collected during the early termination Week 8 visit) will be 
used.  
The analyses will be done using the ITT population and will serve as the primary analysis while 
the analysis of the primary endpoint using the PP population will be used as a supportive analysis. 
7.2 Secondary Efficacy Analyses 
The second efficacy endpoints are:  
- 
Change from baseline in IGA at week 2, 4, and 8 
- 
Change from baseline in EASI at week 2, 4, and 8 
- 
Change from baseline in POEM at week 2, 4, and 8 
- 
Change from baseline in DLQI at week 2, 4, and 8 
- 
Change from baseline in SCORAD at week 2, 4, and 8 
- 
Change from baseline in VAS at week 2, 4, and 8 
- 
Change from baseline in BSA at week 2, 4, and 8 
- 
Proportion of patients achieving at least 1-point decrease in IGA at Week 8 
 
All secondary endpoint based on the change from baseline will be assesd using an ANCOVA 
where the change from baseline will be the dependant variable and including the treatment group 
and site as fixed effects and baseline value as a covariate. In addition, ANCOVA will also be 
performed on the change from baseline at week 10 and on the change from Week 8 to Week 10. 
All secondary endpoint based on categories will be analysed using a Cochran–Mantel–Haenszel 
test stratified by site and the p-value from this test will be presented along with frequency and 
percentage of subjects for each category. 


 
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All change and percent change values will be summarized using descriptive statisitics, for each 
treatment group and visit. Proportion of subjects with no, 1-point, 2-point, 3-point, 
decrease/increase, will be presented at Week 8. 
All statistical analyses will de bone at each visit and using the ITT (primary analysis) and PP 
(supportive analysis) population. All the analyses will be done using observed values. Results 
collected during the early termination visit related to Week 8 and Week 10 will not be included. 
No sensitivity analysis will be done for missing values. 
 
7.3 Exploratory Efficacy Analyses 
Change from baseline in TEWL at week 2, 4, and 8 will be analyzed using an ANCOVA as 
described in section 7.2. 
8 Safety Analyses 
 
Safety analysis will be performed based on the safety analysis population. No inferential statistics 
will be done on safety variables. 
 
Adverse Events 
Treatment-emergent AEs (TEAEs) will be summarized by the number of subjects reporting the 
events, as well as by System Organ Class, Preferred Term, severity, seriousness, and 
relationship to study medication. A general summary table will be provided with the number of 
TEAEs, Related TEAEs, Serious TEAEs and Serious Related TEAEs. 
 
For the summary of TEAEs by severity, each patient will be counted only once within a System 
Organ Class or a Preferred Term by using the TEAEs with the highest intensity within each 
category for each analysis. For the summary of TEAEs by relationship to study medication, each 
patient will be counted only once within a System Organ Class or a Preferred Term by using the 
AEs with the greatest reported relationship within each category. For the summary of AEs by 
relationship to study medication and severity, each patient will be counted only once within a 
System Organ Class or a Preferred Term by using (1) the greatest reported relationship followed 
by (2) the highest reported intensity. 
The following tables will be presented: 
 
TEAEs by SOC/PT; 
 
Related TEAEs by SOC/PT; 
 
TEAEs by severity and SOC/PT; 
 
TEAEs by relationship  and SOC/PT; 
 
TEAEs by relationship/severity and by SOC/PT; 
 
TEAEs leading to treatment discontinuation by SOC/PT 
 
Serious TEAEs (SAEs) by SOC/PT; 
 
Related Serious TEAEs by SOC/PT; 


 
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Clinical Laboratory 
The clinical laboratory results (including value at visit and change from baseline) will be presented 
descriptively for each time point. Shift table from baseline to each post-dose time points will be 
presented. 
Vital Signs 
The vital signs (including value at visit and change from baseline) will be presented descriptively 
for each time point. 
 
Total and Free DGLA plasma levels, Total Fatty Profile and Interleukins levels 
Relationship between DGLA levels and the severity of disease will be looked at. A scatter plot of 
Total and Free DGLA concentrations at baseline versus IGA score at Week 8 and versus change 
from baseline in IGA at Week 8 will be produced by treatment group as well as for both treatment 
combined. Spearman correlation coefficient will be presented. In addition, change from Baseline 
in DGLA versus change from baseline in IGA will also be plotted (along with Spearman correlation 
coefficient) at Week 8 as well as the change from baseline in DGLA at Week 8 versus the change 
from baseline in IGA at Week 10.  
Descriptive statistics of level of DGLA will be presented by treatment, visit and responder status. 
The analysis of the total fatty and interleukins data will not be covered in this SAP. 
 


 
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9 Reporting Conventions 
P-values will be reported to 3 decimal places. If value is less than 0.001, then it will be shown as 
“<0.001”. The mean, SD, Median and inter-quantile will be reported to one decimal place greater 
than the original data. The minimum and maximum will use the same number of decimal places 
as the original data.  
10 Technical Details 
All statistical processing will be performed using SAS® software, Version 9.2, or higher. 
11 Summary of Changes to the Protocol 
Additional analyses (not included in the protocol) were added in the statistical analysis plan. 
- 
Total and Free DGLA plasma level in relation with IGA results 
- 
Respondeur analysis controlling for the information on IGA at Baseline  
- 
Comparability of the discontinuation rates and of the reasons for discontinuation for both 
treatment groups 
12  References 
No applicable.  
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 28 of 107 
 
13 Mock Tables, Listings and Figures 
All tables, listings and figures (TLF) will be generated through SAS. 
The title will be unique for each TLF and self-explanatory. The header section will comprise of the Sponsor’s name, the protocol number, the TLF 
number, the TLF title, the analysis population, and the page number (Page X of Y). The footer section of the table will include the date and time 
of the execution of the program, and the name of the program. All necessary footnotes will be provided to add clarity to the TLF. 
The font will be “Courier New", 8-9 points, or similar. The orientation will be landscape with 1 inch margins. The tables and figures will be placed 
under Appendix 14 in the Clinical Study Report while the listings will be placed in the Appendix 16. 
The following sections display the expected TLFs. All efforts were made to create representative mock TLFs, however, these may change 
depending on the format and layout of the data, without changing the purpose of the presentation. In the event a major change to a TLF is 
required, this will be discussed within the study team and necessary documentation will be created.     
13.1 Mock Tables 
The list of tables is presented in the table below followed by the actual mock tables. 
Table Number 
Title 
Population 
 
Study Conduct Tables 
 
14.1.1 
Summary of Subject Enrollment and Disposition 
All 
14.1.2 
Summary of Visits Completed 
SAF/ITT/PP 
14.1.3 
Summary of Study Completion 
SAF/ITT/PP 
14.1.4 
Summary of Protocol Deviations 
SAF 
14.1.5.1/.2/.3 
Summary of Subject Demographics and Baseline Characteristics 
SAF/ITT/PP 
14.1.6 
Summary of Medical History  
SAF 
14.1.7.1/.2/.3 
Summary of Study Drug Exposure and Compliance 
SAF/ITT/PP 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 29 of 107 
 
Table Number 
Title 
Population 
 
Efficacy Tables 
 
14.2.1.1.1 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 
ITT 
14.2.1.1.2 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 
PP 
14.2.1.1.3 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 – Supportive Analysis (LOCF) 
ITT 
14.2.1.1.4 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 - Supportive Analysis (LOCF) 
PP 
14.2.1.2.1 
Summary of Investigator’s Global Assessment – Actual, Change and Percent Change from Baseline 
ITT 
14.2.1.2.2 
Summary of Investigator’s Global Assessment – Actual, Change and Percent Change from Baseline 
PP 
14.2.1.3.1 
Summary of Investigator’s Global Assessment – Proportion of Subjects with at least 1-point decrease, and with no or 
increase/decrease at Week 8 
ITT 
14.2.1.3.2 
Summary of Investigator’s Global Assessment – Proportion of Subjects with at least 1-point decrease, and with no or 
increase/decrease at Week 8 
PP 
14.2.2.1 
Summary of Eczema Area and Severity Index – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.2.2 
Summary of Eczema Area and Severity Index – Actual, Change, and Percent Change from Baseline 
PP 
14.2.3.1 
Summary of Patient-Oriented Eczema Measure – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.3.2 
Summary of Patient-Oriented Eczema Measure – Actual, Change, and Percent Change from Baseline 
PP 
14.2.4.1 
Summary of Dermatology Quality of Life Index – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.4.2 
Summary of Dermatology Quality of Life Index – Actual, Change, and Percent Change from Baseline 
PP 
14.2.5.1 
Summary of Summary of SCORing Atopic Dermatitis – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.5.2 
Summary of Summary of SCORing Atopic Dermatitis – Actual, Change, and Percent Change from Baseline 
PP 
14.2.6.1 
Summary of Visual Analog Scale of Pruritus – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.6.2 
Summary of Visual Analog Scale of Pruritus – Actual, Change, and Percent Change from Baseline 
PP 
14.2.7.1 
Summary of Body Surface Area – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.7.2 
Summary of Body Surface Area – Actual, Change, and Percent Change from Baseline 
PP 
14.2.8.1 
Summary of Trans epidemal Water Loss – Actual, Change, and Percent Change from Baseline 
ITT 
14.2.8.2 
Summary of Trans epidemal Water Loss – Actual, Change, and Percent Change from Baseline 
PP 
14.2.9.1 
Summary of Total DGLA Concentrations – Actual and Change from Baseline by IGA results  
ITT 
14.2.9.2 
Summary of Free DGLA Concentrations – Actual and Change from Baseline by IGA results  
ITT 
 
 
 
 
 
 
 
Safety Tables 
 
14.3.1.1 
Overall Summary of Adverse Events 
SAF 
14.3.1.2 
Summary of Treatment-Emergent Adverse Events 
SAF 
14.3.1.3 
Summary of Related Treatment-Emergent Adverse Events 
SAF 
14.3.1.4 
Summary of Treatment-Emergent Adverse Events by Severity 
SAF 
14.3.1.5 
Summary of Treatment-Emergent Adverse Events by Relationship 
SAF 
14.3.1.6 
Summary of Treatment-Emergent Adverse Events by Relationship and Severity 
SAF 
14.3.1.7 
Summary of Treatment-Emergent Adverse Events leading to treatment discontinuation 
SAF 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 30 of 107 
 
Table Number 
Title 
Population 
14.3.1.8 
Summary of Serious Treatment-Emergent Adverse Events 
SAF 
14.3.1.9 
Summary of Related Serious Treatment-Emergent Adverse Events 
SAF 
14.3.4.1.1 
Summary  of Clinical Safety Laboratory Results – Serum Chemistry  
SAF 
14.3.4.1.2 
Shift Table Clinical Laboratory – Serum Chemistry  
SAF 
14.3.4.2.1 
Summary  of Clinical Laboratory – Hematology 
SAF 
14.3.4.2.2 
Shift Table Clinical Laboratory  – Hematology 
SAF 
14.3.4.3.1 
Summary  of Clinical Laboratory  – Urinalysis (Continuous) 
SAF 
14.3.4.3.2 
Shift Table Clinical Laboratory – Urinalysis (Continuous) 
SAF 
14.3.4.3.3 
Summary  of Clinical Laboratory – Urinalysis (Categorical) 
SAF 
14.3.5 
Summary of Vital Signs 
SAF 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 31 of 107 
 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.1.1 
Summary of Subject Enrollment and Disposition 
(All Subjects) 
 
 
 
Treatement Group 
 
Parameter 
Statistic 
DS107G 
Placebo 
Total 
Number of Subjects Screened 
N 
 
 
xx 
Number of Subjects Screen Failed 
N 
 
 
xx 
Number of Subjects Randomized 
N 
xx 
xx 
xx 
Number of Subjects in Safety Population1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Subjects in the Intent-to-Treat Population1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Number of Subjects in the Per Protocol Population1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
1 Percentages are based on the number of randomized subjects. 
Note(s): The Safety (SAF) population includes all randomized subjects who received at least one dose of the medication, according to treatment 
received. 
The Intent-To-Treat (ITT) population includes all randomized subjects, according to the randomized treatment. 
The Per Protocol (PP) population includes all subjects who received at least one dose of the medication and who had at least one post-baseline 
evaluation on the primary endpoint of IGA with no significant protocol deviations.  
 
 
 
 
 
Program: t14_1_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 32 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.1.2 
Summary of Visits Completed 
 
 
 
Treatement Group 
 
Parameter 
Statistic 
DS107G 
Placebo 
Total 
Number of Subjects in Safety Population1 
N 
xx 
xx 
xx 
  Screening 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Baseline 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 4 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 8/ET 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Follow up/Week 10 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Number of Subjects in Intent-to-treat Population2 
N 
xx 
xx 
xx 
  Screening 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Baseline 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 4 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 8/ET 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Follow up/Week 10 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Number of Subjects in Per Protocol Population3 
N 
xx 
xx 
xx 
  Screening 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Baseline 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 4 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Week 8/ET 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Follow up/Week 10 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
1 Percentages are based on the number of subjects in the safety population. 
2 Percentages are based on the number of subjects in the intent-to-treat population. 
3 Percentages are based on the number of subjects in the per protocol population. 
 
 
 
 
Program: t14_1_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 33 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 3 
Protocol No. DS107G-02  
 
Table 14.1.3 
Summary of Study Completion 
 
 
 
Treatement Group 
 
Parameter 
Statistic 
DS107G 
Placebo 
Total 
Number of Subjects in Safety Population 
N 
xx 
xx 
xx 
  Completed the study1 
 
 
 
 
     Yes 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     No 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value5 
x.xxx 
 
 
   
 
 
 
 
   
  Primary Reason for Discontinuation4 
 
 
 
 
    Withdrawal by subject 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Protocol violation 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Pregnancy 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Death 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Lost to follow-up 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Adverse event or SAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Physician decision 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Study terminated by sponsor 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value6 
x.xxx 
 
 
 
 
 
 
 
  Number of days in study 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
1 Percentages are based on the number of subjects in the safety population. 
2 Percentages are based on the number of subjects in the intent-to-treat population. 
3 Percentages are based on the number of subjects in the per protocol population. 
4 Percentages are based on the number of subjects who discontinued within each population. 
5 p-value from Fisher Exact test 
6 p-value from a Pearson’s Chi-Square test (using exact statement) 
Note(s): Number of days in the study is calculated as the difference between the date of the last visit (Follow up/Week 10) and the informed 
consent date plus 1. 
 
Program: t14_1_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 34 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 2 of 3 
Protocol No. DS107G-02  
 
Table 14.1.3 
Summary of Study Completion 
 
 
 
Treatement Group 
 
Parameters 
Statistic 
DS107G 
Placebo 
Total 
Number of Subjects in Intent-to-treat Population 
N 
xx 
xx 
xx 
  Completed the study2 
 
 
 
 
     Yes 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     No 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value5 
x.xxx 
 
 
 
 
 
 
 
  Primary Reason for Discontinuation4 
 
 
 
 
    Withdrawal by subject 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Protocol violation 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Pregnancy 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Death 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Lost to follow-up 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Adverse event or SAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Physician decision 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Study terminated by sponsor 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value6 
x.xxx 
 
 
 
 
 
 
 
  Number of days in study 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
1 Percentages are based on the number of subjects in the safety population. 
2 Percentages are based on the number of subjects in the intent-to-treat population. 
3 Percentages are based on the number of subjects in the per protocol population. 
4 Percentages are based on the number of subjects who discontinued within each population. 
5 p-value from Fisher Exact test 
6 p-value from a Pearson’s Chi-Square test (using exact statement) 
Note(s): Number of days in the study is calculated as the difference between the date of the last visit (Follow up/Week 10) and the informed 
consent date plus 1. 
 
Program: t14_1_3.SAS, Generated on DDMMMYYY HH:MM


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 35 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 3 of 3 
Protocol No. DS107G-02  
 
Table 14.1.3 
Summary of Study Completion 
 
 
 
Treatement Group 
 
Parameters 
Statistic 
DS107G 
Placebo 
Total 
Number of Subjects in Per Protocol Population 
N 
xx 
xx 
xx 
  Completed the study3 
 
 
 
 
     Yes 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
     No 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value5 
x.xxx 
 
 
   
 
 
 
 
  Primary Reason for Discontinuation4 
 
 
 
 
    Withdrawal by subject 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Protocol violation 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Pregnancy 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Death 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Lost to follow-up 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Adverse event or SAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Physician decision 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Study terminated by sponsor 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value6 
x.xxx 
 
 
 
 
 
 
 
  Number of days in study 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
1 Percentages are based on the number of subjects in the safety population. 
2 Percentages are based on the number of subjects in the intent-to-treat population. 
3 Percentages are based on the number of subjects in the per protocol population. 
4 Percentages are based on the number of subjects who discontinued within each population. 
5 p-value from Fisher Exact test 
6 p-value from a Pearson’s Chi-Square test (using exact statement) 
Note(s): Number of days in the study is calculated as the difference between the date of the last visit (Follow up/Week 10) and the informed 
consent date plus 1. 
 
Program: t14_1_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 36 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.1.4 
Summary of Protocol Deviations 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Deviations 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
Washout period not respected 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Missed dose(s) 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Extra dose(s) 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Fasting period not respected 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Randomization error 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Study product not kept within temperature range 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Study visit not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Visit performed out of window 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Procedure(s) done but not required by the protocol 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Time window/order/of events for study procedure not 
respected 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Study procedure(s) not done 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Prohibithed Medications 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note(s): n = Number of subjects. Each subject is counted only once within each deviation. 
 
 
Program: t14_1_4.SAS, Generated on DDMMMYYY HH:MM 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 37 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 2 
Protocol No. DS107G-02  
 
Table 14.1.5.1 
Summary of Subject Demographics and Baseline Characteristics 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Characteristic 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
Sex 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Male 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Female 
 
 
 
 
 
 
 
 
 
Age (years) 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
Race 
 
 
 
 
  American Indian/Alaska Native 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Asian 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Black or African American 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Native Hawaiian or Other Pacific Islander 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  White 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Ethnicity 
 
 
 
 
  Hispanic or Latino 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Not Hispanic or Latino 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: t14_1_5_1.SAS, Generated on DDMMMYYY HH:MM 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 38 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 2 of 2 
Protocol No. DS107G-02  
 
Table 14.1.5.1 
Summary of Subject Demographics and Baseline Characteristics 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Characteristic 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
Height (cm) 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
Weight (kg) 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
BMI (kg/m2) 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
Program: t14_1_5_1.SAS, Generated on DDMMMYYY HH:MM 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 39 of 107 
 
Similar tables will be provided for 
Table 14.1.5.2  
Summary of Subject Demographics and Baseline Characteristics (Intent-to-Treat Population) 
 
Table 14.1.5.3  
Summary of Subject Demographics and Baseline Characteristics (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 40 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.1.6 
Summary of Medical History 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Body System 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
  Eyes-Ears-Nose-Throat 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Respiratory – Asthma 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Respiratory – Other 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Cardiovascular 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Gastrointestinal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Hepatobiliary 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Genitourinary/Renal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Reproductive 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Neurological 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Endocrinal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Hematological 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Musculoskeletal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Dermatological 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Extremities 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Immunological 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Psychiatric 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Allergies 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: t14_1_6.SAS, Generated on DDMMMYYY HH:MM 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 41 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.1.7.1 
Summary of Study Drug Exposure and Compliance 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Parameters 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
Number of days on drug 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
Compliance (%) 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Number of days on drug is defined as (Date of Week 8/ET Visit – First dose of study drug administration date) 
Compliance is defined as 100*[(Sum of all capsules dispensed) - (Sum of all capsules returned)]/[4 x Number of days on drug] 
 
 
 
 
Program: t14_1_7_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 42 of 107 
 
Similar tables will be provided for 
Table 14.1.7.2  
Summary of Study Drug Exposure and Compliance (Intent-to-Treat Population) 
 
Table 14.1.7.3  
Summary of Study Drug Exposure and Compliance (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 43 of 107 
 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.2.1.1.1 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 
(Intent-to-Treat Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
 
 
 
 
IGA Score 
 
 
 
 
 Baseline 
 
 
 
 
  3 – Moderate 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  4 – Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  5 – Very Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Week 8 
 
 
 
 
  0 – Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1 – Almost Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2 – Mild 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3 – Moderate 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  4 – Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  5 – Very Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
  Responders1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Non-Responders 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value2 
 
x.xxx 
 
 
 
 
p-value3 
x.xxx 
 
 
 
 
Week 8 – Very Severe/Severe4 
 
 
 
 
 
  0 – Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1 – Almost Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2 – Mild 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3 – Moderate 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  4 – Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  5 – Very Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
  Responders1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Non-Responders 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value2 
x.xxx 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 44 of 107 
 
 
 
 
 
 
 
Week 8 – Moderate4 
 
 
 
 
 
  0 – Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1 – Almost Clear 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2 – Mild 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3 – Moderate 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  4 – Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  5 – Very Severe 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
  Responders1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Non-Responders 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value2 
x.xxx 
 
 
 
 
 
 
 
1 Subject is classified as Responder if he/she achieves an IGA score of 0 (clear) or 1 (almost clear) at Week 8 
2 p-value from a Cochran-Mantel-Haenszel test with site included as a stratification factor 
3 p-value from a Fisher Exact test (data from all sites combined) 
4 IGA score at baseline visit. 
 
 
Program: t14_2_1_1_1.SAS, Generated on DDMMMYYY HH:MM  
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 45 of 107 
 
Similar tables will be provided for 
Table 14.2.1.1.2 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 (Per Protocol Population) 
Table 14.2.1.1.3 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 (Intent-to-Treat Population) Supportive Analysis 
(LOCF) 
Table 14.2.1.1.4 
Summary of Investigator’s Global Assessment – Responder Analysis at Week 8 (Per Protocol Population) Supportive Analysis 
(LOCF) 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 46 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 2 
Protocol No. DS107G-02  
 
Table 14.2.1.2.1 
Summary of Investigator’s Global Assessment – Actual, Change and Percent Change from Baseline 
(Intent-to-Treat Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
IGA Score 
 
 
 
 
 
 
 
 
 
Baseline 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
Week 2 
 
 
 
 
 Actual 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 Change from Baseline 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
LSMEANS1 
xx.x 
xx.x 
 
 
95% CI 
(xx.x, xx.x) 
(xx.x, xx.x) 
 
 
p-value1 
 
 
 
 
 
 
 
 
 Percent Change from Baseline 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 47 of 107 
 
NOTE: Results at Week 4, Week 8, and Week 10 will also be presented as well as the change from Week 8 to Week 10. 
1 LSMEANs and p-value from an ANCOVA on the change from baseline. The model includes Treatment group, Site as fixed effects and the baseline 
value as the covariate. 
Note(s): Baseline is the result measured at Baseline Visit. 
Program: t14_2_1_2_1.SAS, Generated on DDMMMYYY HH:MM  
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 48 of 107 
 
Similar tables will be provided for 
Table 14.2.1.2.2 
Summary of Investigator’s Global Assessment – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.2.1 
Summary of Eczema Area and Severity Index – Actual, Change, and Percent Change from Baseline (Intent-to-Treat Population) 
Table 14.2.2.2  
Summary of Eczema Area and Severity Index – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.3.1 
Summary of Patient-Oriented Eczema Measure – Actual, Change, and Percent Change from Baseline (Intent-to-Treat Population) 
Table 14.2.3.2 
Summary of Patient-Oriented Eczema Measure – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.4.1 
Summary of Dermatology Quality of Life Index – Actual, Change, and Percent Change from Baseline (Intent-to-Treat 
Population) 
Table 14.2.4.2 
Summary of Dermatology Quality of Life Index – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.5.1 
Summary of Summary of SCORing Atopic Dermatitis – Actual, Change, and Percent Change from Baseline (Intent-to-Treat 
Population) 
Table 14.2.5.2 
Summary of Summary of SCORing Atopic Dermatitis – Actual, Change, and Percent Change from Baseline (Per Protocol 
Population) 
Table 14.2.6.1 
Summary of Visual Analog Scale of Pruritus – Actual, Change, and Percent Change from Baseline (Intent-to-Treat Population) 
Table 14.2.6.2 
Summary of Visual Analog Scale of Pruritus – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.7.1  
Summary of Body Surface Area – Actual, Change, and Percent Change from Baseline (Intent-to-Treat Population) 
Table 14.2.7.2  
Summary of Body Surface Area – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
Table 14.2.8.1  
Summary of Trans epidemal Water Loss – Actual, Change, and Percent Change from Baseline (Intent-to-Treat Population) 
Table 14.2.8.2  
Summary of Trans epidemal Water Loss – Actual, Change, and Percent Change from Baseline (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 49 of 107 
 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.2.1.3.1 
Summary of Investigator’s Global Assessment – Proportion of Subjects with 
at least 1-point decrease, and with no change or increase/decrease at Week 8 and Week 10 
(Intent-to-Treat Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
IGA Score 
 
 
 
 
Week 8 
 
 
 
 
 At least a 1-point decrease from baseline in IGA 
 
 
 
 
  Yes 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value1 
x.xxx 
 
 
 Change from Baseline in IGA 
 
 
 
 
  3-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No change 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Week 10 
 
 
 
 
 At least a 1-point decrease from baseline in IGA 
 
 
 
 
  Yes 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
p-value1 
x.xxx 
 
 
 Change from Baseline in IGA 
 
 
 
 
  3-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1-point decrease 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No change 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  3-point increase 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
1 p-value from a Cochran-Mantel-Haenszel test with site included as a stratification factor 
Note(s): Baseline is the result measured at Baseline Visit. 
 
 
Program: t14_2_1_3_1.SAS, Generated on DDMMMYYY HH:MM  
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 50 of 107 
 
Similar table will be provided for 
Table 14.2.1.3.2 
Summary of Investigator’s Global Assessment – Proportion of Subjects with at least 1-point decrease, and with no change or 
increase/decrease at Week 8 and Week 10 (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 51 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of X 
Protocol No. DS107G-02  
 
Table 14.2.9.1 
Summary of Total DGLA Concentrations – Actual and Change from Baseline by IGA results 
(Intent-to-Treat Population) 
 
 
 
Treatement Group 
 
 
 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
 
Parameter 
 
IGA Responder status1 
Total DGLA 
 
 
Responder 
Non 
Responder 
Responder 
Non 
Responder Responder 
Non 
Responder 
 
Statistic 
 
 
 
 
 
 
Baseline 
n 
 
xx 
 
xx 
 
xx 
 
Mean 
 
xx.x 
 
xx.x 
 
xx.x 
 
SD 
 
xx.x 
 
xx.x 
 
xx.x 
 
Median 
 
xx.x 
 
xx.x 
 
xx.x 
 
Min, Max 
 
xx, xx 
 
xx, xx 
 
xx, xx 
 
Interquartile 
 
xx, xx 
 
xx, xx 
 
xx, xx 
Week 4 
 
 
 
 
 
 
 
 Actual 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 Change from Baseline 
n 
xx 
xx 
xx 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NOTE: Results at Week 8 will also be presented as well as the change from Week 8 for DGLA result by IGA results at Week 10. 
1IGA resuls for the corresponding visit 
Note(s): Baseline is the nearest value to and before the first dose of the study medication. 
 
Program: t14_2_9_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 52 of 107 
 
Similar table will be provided for 
Table 14.2.9.2 
Summary of Free DGLA Concentrations – Actual and Change from Baseline by IGA results (Intent-to-treat Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of 1 
Protocol No. DS107G-02  
 
Table 14.3.1.1 
Overall Summary of Adverse Events 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic1 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
Number of Subjects with Treatment-Emergent Adverse Events 
n(%)  E 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
Number of Subjects with Related Treatment-Emergent Adverse Events 
n(%)  E 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
Number of Subjects with Serious Treatment-Emergent Adverse Events 
n(%)  E 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
Number of Subjects with Related Serious Treatment-Emergent 
Adverse Events 
n(%)  E 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
Number of Subjects with Treatment-Emergent Adverse Events leading 
to treatment discontinuation 
n(%)  E 
xx (xx.x) xx 
xx (xx.x) xx 
xx (xx.x) xx 
 
 
 
 
 
1 n=number of subjects; E=number of events 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0) 
 
 
 
 
Program: t14_3_1_1.SAS, Generated on DDMMMYYY HH:MM  
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 54 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
 
Table 14.3.1.2 
Summary of Treatment-Emergent Adverse Events 
(Safety Population) 
 
 
 
Treatement Group 
 
System Organ Class 
    Preferred Term 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
Number of subjects with at least one TEAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
SOC1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
SOC2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). Subjects experiencing the same adverse event multiple times within the 
same system organ class are counted only once for that system organ class. Similarly, subjects experiencing the same adverse event multiple times 
within the same preferred term are counted only once. Adverse events are sorted alphabetically by system organ class and within each system organ 
class, the preferred terms are presented by decreasing order of total frequency. 
 
 
 
 
Program: t14_3_1_2.SAS, Generated on DDMMMYYY HH:MM  
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 55 of 107 
 
Similar tables will be provided for 
Table 14.3.1.3 
Summary of Related Treatment-Emergent Adverse Events (Safety Population) 
Table 14.3.1.7 
Summary of Treatment-Emergent Adverse Events leading to treatment discontinuation (Safety Populaiton) 
Table 14.3.1.8 
Summary of Serious Treatment-Emergent Adverse Events (Safety Population) 
Table 14.3.1.9 
Summary of Related Serious Treatment-Emergent Adverse Events (Safety Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 56 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.1.4 
Summary of Treatment-Emergent Adverse Events by Severity 
(Safety Population) 
 
 
 
Treatement Group 
 
System Organ Class 
    Preferred Term 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Mild 
Moderate 
Severe 
Mild 
Moderate 
Severe 
Number of subjects with at least one TEAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). Subjects experiencing the same adverse event multiple times within the 
same system organ class are counted only once according to the highest severity for that system organ class. Similarly, subjects experiencing the 
same adverse event multiple times within the same preferred term are counted only once according to the highest severity. Adverse events are 
sorted alphabetically by system organ class and within each system organ class, the preferred terms are presented by decreasing order of total 
frequency. 
 
 
 
Program: t14_3_1_4.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 57 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.1.5 
Summary of Treatment-Emergent Adverse Events by Relationship 
(Safety Population) 
 
 
 
Treatement Group 
 
System Organ Class 
    Preferred Term 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Related 
 
Not Related 
Related 
 
Not Related 
Number of subjects with at least one TEAE 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC1 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC2 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
 
xx (xx.x) 
xx (xx.x) 
 
xx (xx.x) 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). Subjects experiencing the same adverse event multiple times within the 
same system organ class are counted only once according to the greatest reported relationship for that system organ class. Similarly, subjects 
experiencing the same adverse event multiple times within the same preferred term are counted only once according to the greatest reported 
relationship. Adverse events are sorted alphabetically by system organ class and within each system organ class, the preferred terms are 
presented by decreasing order of total frequency. 
 
 
 
Program: t14_3_1_5.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 58 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.1.6 
Summary of Treatment-Emergent Adverse Events by Relationship and Severity 
(Safety Population) 
 
 
 
Treatement Group 
 
System Organ Class 
    Preferred Term 
 
Statistic 
DS107G 
(N=XX) 
Mild 
Moderate 
Severe 
Related 
Not Related 
Related 
Not Related 
Related 
Not Related 
Number of subjects with at least 
one TEAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). Subjects experiencing the same adverse event multiple times within the 
same system organ class are counted only once Term by using (1) the greatest reported relationship followed by (2) the highest reported intensity 
for that system organ class. Similarly, subjects experiencing the same adverse event multiple times within the same preferred term are counted 
only once Term by using (1) the greatest reported relationship followed by (2) the highest reported intensity. Adverse events are sorted 
alphabetically by system organ class and within each system organ class, the preferred terms are presented by decreasing order of total 
frequency. 
 
 
 
Program: t14_3_1_6.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 59 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.1.6 
Summary of Treatment-Emergent Adverse Events by Relationship and Severity 
(Safety Population) 
 
 
 
Treatement Group 
 
System Organ Class 
    Preferred Term 
 
Statistic 
Placebo 
(N=XX) 
Mild 
Moderate 
Severe 
Related 
Not Related 
Related 
Not Related 
Related 
Not Related 
Number of subjects with at least 
one TEAE 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
SOC2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). Subjects experiencing the same adverse event multiple times within the 
same system organ class are counted only once Term by using (1) the greatest reported relationship followed by (2) the highest reported intensity 
for that system organ class. Similarly, subjects experiencing the same adverse event multiple times within the same preferred term are counted 
only once Term by using (1) the greatest reported relationship followed by (2) the highest reported intensity. Adverse events are sorted 
alphabetically by system organ class and within each system organ class, the preferred terms are presented by decreasing order of total 
frequency. 
 
 
 
Program: t14_3_1_6.SAS, Generated on DDMMMYYY HH:MM 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 60 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.4.1.1 
Summary of Clinical Laboratory – Serum Chemistry 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
ALT (IU/L ) 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
 Actual 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
Baseline 
 
 
 
 
 Actual 
n 
xx 
xx 
Xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
Week 4 
 
 
 
 
 Actual 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 Change from Baseline 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
NOTES: Results at Week 8 will also be presented. See Table 
1 for details on parameters to be presented 
 
 
 
 
Note(s): Baseline is the nearest value to and before the first dose of the study medication. 
 
Program: t14_3_4_1_1.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 61 of 107 
 
Similar tables will be provided for 
Table 14.4.2.1 Summary of Clinical Laboratory – Hematology (Safety Population) 
Table 14.4.3.1 Summary of Clinical Laboratory – Urinalysis (Continuous) (Safety Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 62 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.4.1.2 
Shift Table Clinical Laboratory – Serum Chemistry 
(Safety Population) 
 
 
 
 
Treatement Group 
Parameter 
Post-Baseline 
Laboratory 
Evaluation 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Baseline Laboratory Evaluation 
Baseline Laboratory Evaluation 
Low 
Normal 
High 
Low 
Normal 
High 
ALT (IU/L ) 
 
 
 
 
 
 
 
 
Week 4 
Low 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Normal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
High 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
Week 8 
Low 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Normal 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
High 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NOTE: See Table 1 for details on parameters to be presented. 
 
 
 
 
 
Note(s): Baseline is the nearest value to and before the first dose of the study medication. 
 
Program: t14_3_4_1_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 63 of 107 
 
Similar tables will be provided for 
Table 14.4.2.2 Shift Table Clinical Laboratory – Hematology (Safety Population) 
Table 14.4.3.2 Shift Table Clinical Laboratory – Urinalysis (Continuous) (Safety Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 64 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.4.3.3 
Summary of Clinical Laboratory – Urinalysis (Categorical) 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
Bilirubin 
 
 
 
 
 
 
 
 
 
Screening 
 
 
 
 
  Positive 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Negative 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
 
  Positive 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Negative 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
Week 4 
 
 
 
 
  Positive 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Negative 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
 
 
 
Week 8 
 
 
 
 
  Positive 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Negative 
n (%) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
NOTE: See Table 1 for details on parameters to be presented. 
 
 
 
 
 
 
Program: t14_3_4_3_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 65 of 107 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
Table 14.3.5 
Summary of Vital Signs 
(Safety Population) 
 
 
 
Treatement Group 
 
 
Parameter 
 
Statistic 
DS107G 
(N=XX) 
Placebo 
(N=XX) 
Total 
(N=XX) 
Systolic Blood Pressure (mmHg) 
 
 
 
 
 
 
 
 
 
Screening 
n 
xx 
xx 
xx 
 Actual 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
Baseline 
 
 
 
 
 Actual 
n 
xx 
xx 
Xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
Week 2 
 
 
 
 
 Actual 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 Change from Baseline 
n 
xx 
xx 
xx 
 
Mean 
xx.x 
xx.x 
xx.x 
 
SD 
xx.x 
xx.x 
xx.x 
 
Median 
xx.x 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
Interquartile 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
NOTES: Results at Week 4 and Week 8 will also be presented. All parameters (systolic/diastolic blood pressure, pulse, oral temperature 
and respiratory rate) all be presented. 
Note(s): Baseline is the nearest value to and before the first dose of the study medication. 
 
Program: t14_3_5.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 66 of 107 
 
13.2 Mock Listings 
The list of listings is presented in the table below followed by the actual mock listings. In all listings will appear the subject identification and the 
population indicator. They will be sorted by treatment group, study site, subject, and visit (when applicable). 
Listing 
Number 
Title 
Population 
 
Study Conduct Listings 
 
16.2.1.1.1 
Subject Disposition 
Screen Failures 
16.2.1.1.2 
Subject Disposition  
Enrolled 
16.2.1.2 
Subject Visits 
Enrolled 
16.2.2 
Protocol Deviations 
Enrolled 
16.2.3 
Analysis Populations 
Enrolled 
16.2.4.1 
Demographics and Baseline Characteristics 
Enrolled 
16.2.4.2 
Medical History  
Enrolled 
16.2.4.3 
Prior and Concomitant Medications  
Enrolled 
16.2.4.4 
Other Procedures 
Enrolled 
16.2.4.5 
Emollient 
Enrolled 
16.2.5.1 
Study Drug Administration 
Enrolled 
16.2.5.2 
Drug Accountability 
Enrolled 
16.2.5.3 
Subject Compliance Log 
Enrolled 
16.2.5.4 
Study Drug Exposure and Compliance 
Enrolled 
16.2.5.5 
Total and Free DGLA plasma concentrations 
Enrolled 
 
Efficacy Listings 
 
16.2.6.1 
Investigator’s Global Assessment 
Enrolled 
16.2.6.2 
Eczema Area and Severity Index 
Enrolled 
16.2.6.3 
Patient-Oriented Eczema Measure 
Enrolled 
16.2.6.4 
Dermatology Quality of Life Index 
Enrolled 
16.2.6.5 
SCORing Atopic Dermatitis 
Enrolled 
16.2.6.6 
Trans epidemal Water Loss 
Enrolled 
 
Safety Listings / Other Listings 
 
16.2.7 
Adverse Events 
Enrolled 
16.2.8.1 
Clinical Laboratory 
Enrolled 
16.2.8.2 
Clinical Laboratory – Abnormal Results 
Enrolled 
16.2.9 
Vital Signs 
Enrolled 
16.2.10 
Physical Examination 
Enrolled 
16.2.11 
Additional Information 
Enrolled 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.1.1.1 
Subject Disposition 
(Screen Failed Subjects) 
Site ID 
Subject ID 
Signature ICF 
Meet All 
Inclusion/Exclusion 
Criteria 
Criteria Not Meet 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_1_1_1.SAS, Generated on DDMMMYYY HH:MM 
 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.1.1.2 
Subject Disposition 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Signature 
ICF 
Randomization 
Date 
Randomization 
Number 
Completed 
the study? 
Date of Completion/ 
Discontinuation 
Primary Reason for 
Discontinuation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_1_1_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.1.2 
Subject Visits 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Screening 
Baseline 
Week 2 
Week 4 
Week 8/ET 
Follow up/Week 10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_1_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.2 
Protocol Deviations 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Date Reported 
Category 
Deviation 
Impact 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.3 
Analysis Population 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Intent-to-
Treat 
Population 
Safety 
Populaiton 
Per Protocol 
Population  
Reason not included in 
Intent-to-treat Population/ 
Safety Population/ 
Per Protocol Population 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.4.1 
Demographic and Baseline Characteristics 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
DOB 
Age (years) 
Gender 
Race 
Ethnicity 
Height (cm) Weight (kg) BMI (kg/m2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_4_1.SAS, Generated on DDMMMYYY HH:MM 
 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.4.2 
Medical History 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Body System 
Medical/Surgical term 
Onset 
Date 
Ongoing 
Resolution 
Date 
Improved 
from 
Baseline at 
Week 8 
Visit 
Improved 
from 
Baseline at 
Week 10 
Visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_4_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.4.3 
Prior and Concomitant Medications 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Medication/ 
ATC Classification 
Indication 
Dose/ 
Freq/ 
Route 
Start Date 
Ongoing 
Stop Date 
Prior or 
Concomitant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Medications are coded using WHO-Drug dictionary (version June 2013 B2). 
 
Program: L16_2_4_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.4.4 
Other Procedures 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Procedure 
Indication 
Start Date 
Ongoing 
Stop Date 
Prior or 
Concomitant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_4_4.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.4.5 
Emollient 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Emollient Name 
Start Date 
Ongoing 
Stop Date 
Prior or 
Concomitant 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_4_5.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.5.1 
Study Drug Admnistration 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Was Study Drug 
Administered? 
If no, Reason 
Administration 
Date 
Administration 
Time 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_5_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.5.2 
Drug Accountability 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Date 
Dispensed 
Batch Number 
Capsules 
Dispensed 
Date 
returned 
Capsules 
Returned 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_5_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.5.3 
Subject Compliance Log 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Missing doses 
since last 
visit?  
If Yes, 
Number of 
missed doses 
Comment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_5_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.5.4 
Study Drug Exposure and Compliance 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Number of 
days on drug 
Compliance (%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_5_4.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.5.5 
Total and Free DGLA plasma concentrations 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Analyte 
Visit 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_5_5.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.1 
Investigator’s Global Assessment 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.2 (Part 1) 
Eczema Area and Severity Index 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Erythema 
Head 
Upper 
Extremities 
Trunk 
Lower 
Extremities 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.2 (Part 2) 
Eczema Area and Severity Index 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Induration 
Head 
Upper 
Extremities 
Trunk 
Lower 
Extremities 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.2 (Part 3) 
Eczema Area and Severity Index 
(Enrolled Subjects) 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Excoriation 
Head 
Upper 
Extremities 
Trunk 
Lower 
Extremities 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_2.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.2 (Part 4) 
Eczema Area and Severity Index 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Lichenification  
 
Head 
Upper 
Extremities 
Trunk 
Lower 
Extremities 
EASI Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_2.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.3 
Patient-Oriented Eczema Measure  
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Q1 
Q2 
Q3 
Q4 
Q5 
Q6 
Q7 
POEM Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_3.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.4 (Part 1) 
Dermatology Quality of Life Index 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Q1 
Q2 
Q3 
Q4 
Q5 
Q6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_4.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.4 (Part 2) 
Dermatology Quality of Life Index 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Q7 
Q7A 
Q8 
Q9 
Q10 
DLQI Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_4.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.5 (Part 1) 
SCORing Atopic Dermatitis 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Erythema 
Intensity 
Edema/Papulation 
Intensity 
Oozing/Crust 
Intensity 
Excoriation 
Intensity 
Lichenification 
Intensity 
Dryness 
Intensity 
Total 
Intensity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_5.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.5 (Part 2) 
SCORing Atopic Dermatitis 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Extent 
Area involved (BSA) 
Pruritus VAS 
Symptom Score 
Sleep loss 
VAS Symptom 
Score 
Objective 
SCORAD 
SCORAD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_5.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.6.6 
Trans Epithelial Water Loss 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Area 
Represented Area 
Measurement 
(g/m2h) 
Control Area 
Control 
Measurement 
(g/m2h) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_6_6.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.7 
Adverse Events 
(Enrolled Subjects) 
 
Treatment 
Group 
Subject ID 
System Organ Class/ 
Preferred Term/ 
Verbatim 
Onset Date 
End 
Date 
Onset 
Day 
Dur. 
Severity/ 
Relationship/ 
Outcome 
Action 
Taken 
Drug 
Action 
Taken 
Subject 
SAE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): Adverse events are coded using MedDRA dictionary (version 17.0). *Treatment-Emergent Adverse Event. Dur.=Duration. Severity: Mild; Mod.= 
Moderate; Sev.=Severe. Relationship: Rel.=Related; Not Rel.=Not Related. Outcome: Rec/Res= Recovered/Resolved; Rec/Res. Seq= Recovered/Resolved 
with Sequelae; Recing/Resing= Recovering/Resolving; NotRec/NotRes= Not Recovered/ NotResolved; Unk=Unknown. Action Taken Drug: NotChg=Dose not 
changed; Inter.=Treatment interrupted; Withdr.=Treatment Withdrawn; NA=Not applicable; Unk.=Unknown; Oth.=Other. Action Taken Subject: NotReq=Not 
required; TrtUsed.=Treatment used; Withdr.=Subject Withdrawn; Unk.=Unknown; Oth.=Other.   
 
 
 
 
Program: L16_2_7.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.8.1 
Clinical Laboratory 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Category 
Laboratory Test 
(units) 
Normal Range 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): (L)=Below normal range; (H)=Above normal range   
 
Program: L16_2_8_1.SAS, Generated on DDMMMYYY HH:MM 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.8.2 
Clinical Laboratory – Abnormal Results 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Category 
Laboratory Test 
(units) 
Normal Range 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note(s): (L)=Below normal range; (H)=Above normal range   
 
Program: L16_2_8_2.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.9 
Vital Signs 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Parameter 
(units) 
Result 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_9.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.10 
Physical Examination 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Visit 
Body System 
Results 
Description of 
Abnormality 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_10.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Lisintg 16.2.10 
Physical Examination 
(Enrolled Subjects) 
 
Treatment 
Group 
Site ID 
Subject ID 
Was there any 
additional 
information 
Visit 
Form 
Comments/Clarifications 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Program: L16_2_11.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 99 of 107 
 
13.3 Mock Figures 
The list of Figures is presented in the table below followed by the actual mock. 
Figure 
Number 
Title 
Population 
 
 
 
14.2.1.1.1 
Bar Chart of the Number of Subjects on the Change from Baseline in IGA during study 
ITT 
14.2.1.1.2 
Bar Chart of the Number of Subjects on the Change from Baseline in IGA during study 
PP 
14.2.1.2.1 
Mean Change from baseline in IGA during study 
ITT 
14.2.1.2.2 
Mean Change from baseline in IGA during study 
PP 
14.2.1.3.1 
Mean Percent Change from baseline in IGA during study 
ITT 
14.2.1.3.2 
Mean Percent Change from baseline in IGA during study 
PP 
14.2.2.1.1 
Mean Change from baseline in EASI during study 
ITT 
14.2.2.1.2 
Mean Change from baseline in EASI during study 
PP 
14.2.2.2.1 
Mean Percent Change from baseline in EASI during study 
ITT 
14.2.2.2.2 
Mean Percent Change from baseline in EASI during study 
PP 
14.2.3.1.1 
Mean Change from baseline in POEM during study 
ITT 
14.2.3.1.2 
Mean Change from baseline in POEM during study 
PP 
14.2.3.2.1 
Mean Percent Change from baseline in POEM during study 
ITT 
14.2.3.2.2 
Mean Percent Change from baseline in POEM during study 
PP 
14.2.4.1.1 
Mean Change from baseline in DLQI during study 
ITT 
14.2.4.1.2 
Mean Change from baseline in DLQI during study 
PP 
14.2.4.2.1 
Mean Percent Change from baseline in DLQI during study 
ITT 
14.2.4.2.2 
Mean Percent Change from baseline in DLQI during study 
PP 
14.2.5.1.1 
Mean Change from baseline in SCORAD during study 
ITT 
14.2.5.1.2 
Mean Change from baseline in SCORAD during study 
PP 
14.2.5.2.1 
Mean Percent Change from baseline in SCORAD during study 
ITT 
14.2.5.2.2 
Mean Percent Change from baseline in SCORAD during study 
PP 
14.2.6.1.1 
Mean Change from baseline in VAS during study 
ITT 
14.2.6.1.2 
Mean Change from baseline in VAS during study 
PP 
14.2.6.2.1 
Mean Percent Change from baseline in VAS during study 
ITT 
14.2.6.2.2 
Mean Percent Change from baseline in VAS during study 
PP 
14.2.7.1.1 
Mean Change from baseline in BSA during study 
ITT 
14.2.7.1.2 
Mean Change from baseline in BSA during study 
PP 
14.2.7.2.1 
Mean Percent Change from baseline in BSA during study 
ITT 
14.2.7.2.2 
Mean Percent Change from baseline in BSA during study 
PP 
 
 
 
 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Figure 
Number 
Title 
Population 
 
 
 
14.2.8.1.1 
Mean Change from baseline in TEWL during study 
ITT 
14.2.8.1.2 
Mean Change from baseline in TEWL during study 
PP 
14.2.8.2.1 
Mean Percent Change from baseline in TEWL during study 
ITT 
14.2.8.2.2 
Mean Percent Change from baseline in TEWL during study 
PP 
14.2.9.1 
Scatter Plot of Total DGLA concentrations at Baseline versus IGA score at Week 8 
ITT 
14.2.9.2 
Scatter Plot of Free DGLA concentrations at Baseline versus IGA score at Week 8 
ITT 
14.2.10.1 
Scatter Plot of Change from Baseline Total DGLA concentrations at Week 8versus IGA score at Week 8 
ITT 
14.2.10.2 
Scatter Plot of Change from Baseine Free DGLA concentrations at Week 8 versus IGA score at Week 8 
ITT 
14.2.11.1 
Scatter Plot of Change from Baseline Total DGLA concentrations at Week 8 versus IGA score at Week 10 
ITT 
14.2.11.2 
Scatter Plot of Change from Baseline Free DGLA concentrations at Week 8 versus IGA score at Week 10 
ITT 
 
 
 
 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Figure 14.2.1.1.1 
Bar Chart of the Number of Subjects on the Change from Baseline in IGA during study 
(Intent-to-Treat Population) 
Treatment: DGLA 
 
 
Program: F14_2_1_1_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 102 of 107 
 
Similar Figure will be provided for 
14.2.1.1.2 
Bar Chart of the Number of Subjects on the Change from Baseline in IGA during study (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
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Figure 14.2.1.2.1 
Mean Change from baseline in IGA during study 
(Intent-to-Treat Population) 
 
 
Program: F14_2_1_2_1.SAS, Generated on DDMMMYYY HH:MM 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 104 of 107 
 
Similar Figures will be provided for 
14.2.1.2.2 
Mean Change from baseline in IGA during study (Per Protocol Population) 
14.2.1.3.1 
Mean Percent Change from baseline in IGA during study (Intent-to-Treat Population) 
14.2.1.3.2 
Mean Percent Change from baseline in IGA during study (Per Protocol Population) 
14.2.2.1.1 
Mean Change from baseline in EASI during study (Intent-to-Treat Population) 
14.2.2.1.2 
Mean Change from baseline in EASI during study (Per Protocol Population) 
14.2.2.2.1 
Mean Percent Change from baseline in EASI during study (Intent-to-Treat Population) 
14.2.2.2.2 
Mean Percent Change from baseline in EASI during study (Per Protocol Population) 
14.2.3.1.1 
Mean Change from baseline in POEM during study (Intent-to-Treat Population) 
14.2.3.1.2 
Mean Change from baseline in POEM during study (Per Protocol Population) 
14.2.3.2.1 
Mean Percent Change from baseline in POEM during study (Intent-to-Treat Population) 
14.2.3.2.2 
Mean Percent Change from baseline in POEM during study (Per Protocol Population) 
14.2.4.1.1 
Mean Change from baseline in DLQI during study (Intent-to-Treat Population) 
14.2.4.1.2 
Mean Change from baseline in DLQI during study (Per Protocol Population) 
14.2.4.2.1 
Mean Percent Change from baseline in DLQI during study (Intent-to-Treat Population) 
14.2.4.2.2 
Mean Percent Change from baseline in DLQI during study (Per Protocol Population) 
14.2.5.1.1 
Mean Change from baseline in SCORAD during study (Intent-to-Treat Population) 
14.2.5.1.2 
Mean Change from baseline in SCORAD during study (Per Protocol Population) 
14.2.5.2.1 
Mean Percent Change from baseline in SCORAD during study (Intent-to-Treat Population) 
14.2.5.2.2 
Mean Percent Change from baseline in SCORAD during study (Per Protocol Population) 
14.2.6.1.1 
Mean Change from baseline in VAS during study (Intent-to-Treat Population) 
14.2.6.1.2 
Mean Change from baseline in VAS during study (Per Protocol Population) 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 105 of 107 
 
14.2.6.2.1 
Mean Percent Change from baseline in VAS during study (Intent-to-Treat Population) 
14.2.6.2.2 
Mean Percent Change from baseline in VAS during study (Per Protocol Population) 
14.2.7.1.1 
Mean Change from baseline in BSA during study (Intent-to-Treat Population) 
14.2.7.1.2 
Mean Change from baseline in BSA during study (Per Protocol Population) 
14.2.7.2.1 
Mean Percent Change from baseline in BSA during study (Intent-to-Treat Population) 
14.2.7.2.2 
Mean Percent Change from baseline in BSA during study (Per Protocol Population) 
14.2.8.1.1 
Mean Change from baseline in TEWL during study (Intent-to-Treat Population) 
14.2.8.1.2 
Mean Change from baseline in TEWL during study (Per Protocol Population) 
14.2.8.2.1 
Mean Percent Change from baseline in TEWL during study (Intent-to-Treat Population) 
14.2.8.2.2 
Mean Percent Change from baseline in TEWL during study (Per Protocol Population) 
 
 


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 106 of 107 
 
 
Dignity Sciences 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 1 of x 
Protocol No. DS107G-02  
 
 
Figure 14.2.9.1 
Scatter Plot of Total DGLA concentrations at Baseline versus IGA score at Week 8 
(Intent-to-Treat Population) 
Treatment: DGLA 
Spearman Correlation Coefficient: x.xxx 
 
 
 
Program: F14_2_9_1.SAS, Generated on DDMMMYYY HH:MM 
0
1
2
3
4
5
0
200
400
600
800
1000
1200
1400
IGA (Week 8)
Total DGLA Concentrations (Baseline)


 
SAP version FINAL 1.0: DS107G-02                                                                         19 OCT 2015 
 
 
 
 
Page 107 of 107 
 
Similar Figures will be provided for 
14.2.9.2 
Scatter Plot of Free DGLA concentrations at Baseline versus IGA score at Week 8 (Intent-to-Treat Population) 
14.2.10.1 
Scatter Plot of Change from Baseline Total DGLA concentrations at Week 8versus IGA score at Week 8 (Intent-to-Treat Population) 
14.2.10.2 
Scatter Plot of Change from Baseine Free DGLA concentrations at Week 8 versus IGA score at Week 8 (Intent-to-Treat Population) 
14.2.11.1 
Scatter Plot of Change fdrom Baseline Total DGLA concentrations at Week 8 versus IGA score at Week 10 (Intent-to-Treat Population) 
14.2.11.2 
Scatter Plot of Change fdrom Baseline Free DGLA concentrations at Week 8 versus IGA score at Week 10 (Intent-to-Treat Population)