Conditions: Atopic Dermatitis
Keywords: eczema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 244
Healthy volunteers: no

Brief summary:
This is a randomized double-blind/placebo study evaluate the efficacy of ASN002 in subjects with moderate to severe atopic dermatitis (AD).

Detailed description:
This is a placebo controlled study where subjects with moderate to severe atopic dermatitis will be randomized (1:1:1:1) to receive ASN002 at 40 mg, 60 mg, or 80 mg, or placebo once daily for 12 weeks. Eligible subjects will get the opportunity to enroll in the 24 month open-label extension study (OLE). There will be a 4-week follow up period for subjects not participating in the OLE study. This study will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling and three or four biopsies from subjects who consent.

Arms:
arm 1: 40 mg ASN002 arm 2: 60 mg ASN002 arm 3: 80 mg ASN002 arm 4: Matching placebo for ASN002 doses

Interventions: intervention 1: ASN002 intervention 2: Placebo Oral Tablet
Intervention descriptions: intervention 1: Daily dose of ASN002 for 12 weeks intervention 2: Placebo of ASN002 for 12 weeks

Protocol document:
Prot_002.pdf: 


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TABLE OF CONTENTS 
TABLE OF CONTENTS ................................................................................................................ 2 
PROTOCOL VERSION HISTORY ............................................................................................... 6 
STATEMENT OF COMPLIANCE ................................................................................................ 8 
SIGNATURE PAGE ...................................................................................................................... 9 
PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE .......................................... 10 
LIST OF ABBREVIATIONS ....................................................................................................... 11 
1 
PROTOCOL SUMMARY ............................................................................................ 13 
1.1 
Synopsis ........................................................................................................................ 13 
1.2 
Study Diagram .............................................................................................................. 22 
1.3 
Schedule of Events ........................................................................................................ 22 
2 
INTRODUCTION ........................................................................................................ 25 
2.1 
Background ................................................................................................................... 25 
 
Atopic Dermatitis .................................................................................................. 25 
 
ASN002 in Atopic Dermatitis ................................................................................ 25 
 
Study Rationale ..................................................................................................... 26 
2.2 
Risk/Benefit Assessment ............................................................................................... 26 
 
Known Potential Risks .......................................................................................... 26 
 
Known Potential Benefits ...................................................................................... 27 
 
Assessment of Risks and Benefits .......................................................................... 27 
3 
OBJECTIVES AND ENDPOINTS .............................................................................. 28 
4 
STUDY DESIGN .......................................................................................................... 30 
4.1 
Overall Design .............................................................................................................. 30 
4.2 
Scientific Rationale for Study Design ........................................................................... 31 
4.3 
End of Study Definition ................................................................................................ 31 
4.4 
Safety 
Monitoring 
Criteria 
for 
Individual 
Subject 
Treatment 
Interruption/Discontinuation ......................................................................................... 31 
 
Interruption criteria .............................................................................................. 32 
 
Permanent study discontinuation .......................................................................... 32 
4.5 
Data and Safety Monitoring Board ............................................................................... 32 
5 
STUDY POPULATION ............................................................................................... 33 
5.1 
Inclusion Criteria ........................................................................................................... 33 
5.2 
Exclusion Criteria ......................................................................................................... 34 


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5.3 
Discontinuation and Lost to Follow-Up ........................................................................ 37 
 
Discontinuation ..................................................................................................... 37 
 
Lost to Follow-Up ................................................................................................. 38 
5.4 
Screen Failures .............................................................................................................. 39 
6 
TREATMENT .............................................................................................................. 40 
6.1 
Study Products Administered ........................................................................................ 40 
 
Missed or Vomited Doses...................................................................................... 40 
 
Duration of Treatment .......................................................................................... 41 
6.2 
Preparation/Handling/Storage/Accountability .............................................................. 41 
 
Preparation/Storage/Handling ............................................................................. 41 
 
Accountability ....................................................................................................... 41 
6.3 
Randomization .............................................................................................................. 41 
 
Blinding ................................................................................................................. 42 
 
Study Product Compliance ................................................................................... 42 
6.4 
Concomitant Therapy .................................................................................................... 43 
 
Permitted Therapies .............................................................................................. 43 
 
Prohibited Therapies or Procedures .................................................................... 44 
 
Concomitant Use of Drugs that may affect Gastric pH ........................................ 45 
 
Study Restrictions.................................................................................................. 46 
7 
STUDY ASSESSMENTS AND PROCEDURES ........................................................ 47 
7.1 
Efficacy Assessments .................................................................................................... 47 
 
Eczema Area and Severity Index ........................................................................... 47 
 
Investigator Global Assessment ............................................................................ 47 
 
SCORing Atopic Dermatitis .................................................................................. 47 
 
Body Surface Area ................................................................................................ 47 
 
Pruritus Numeric Rating Scale ............................................................................. 48 
 
5D-Pruritus Scale ................................................................................................. 48 
7.2 
Quality-of-Life Assessments ......................................................................................... 48 
 
Patient-Oriented Eczema Measure ....................................................................... 48 
 
Dermatology Life Quality Index Questionnaire ................................................... 49 
7.3 
Safety Assessments ....................................................................................................... 49 
 
Vital Signs ............................................................................................................. 49 
 
Physical Examination ........................................................................................... 49 
 
Brief Physical Examination .................................................................................. 50 
 
Clinical Laboratory Tests ..................................................................................... 50 
 
Electrocardiogram ................................................................................................ 51 
7.4 
Pharmacokinetic and Pharmacodynamic Assessments ................................................. 52 


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Pharmacokinetics Assessments ............................................................................. 52 
 
Pharmacodynamics Assessments .......................................................................... 52 
 
PK/PD Relationship Assessments ......................................................................... 52 
 
Skin Biopsies ......................................................................................................... 53 
7.5 
Other Assessments ........................................................................................................ 53 
 
Medical Photography............................................................................................ 53 
7.6 
Adverse Events and Serious Adverse Events ............................................................... 54 
 
Definition of Adverse Event .................................................................................. 54 
 
Definition of Treatment-Emergent Adverse Event ................................................ 54 
 
Definition of Serious Adverse Event ..................................................................... 54 
 
Classification of an Adverse Event ....................................................................... 55 
 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 56 
 
Adverse Event Reporting....................................................................................... 56 
 
Serious Adverse Events Reporting ........................................................................ 57 
 
Pregnancy Reporting ............................................................................................ 58 
 
Overdose ............................................................................................................... 58 
8 
STATISTICAL CONSIDERATIONS .......................................................................... 59 
8.1 
Sample Size Determination ........................................................................................... 59 
8.2 
Populations for Analyses .............................................................................................. 59 
8.3 
Statistical Analyses ....................................................................................................... 60 
 
General Approach ................................................................................................. 60 
 
Efficacy Analyses .................................................................................................. 60 
 
Safety Analyses...................................................................................................... 61 
 
Pharmacokinetic Analyses .................................................................................... 61 
 
Pharmacodynamic Analyses ................................................................................. 62 
 
Other Analyses ...................................................................................................... 62 
 
Planned Interim Analysis ...................................................................................... 62 
9 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS .... 63 
9.1 
Local Regulations/Declaration of Helsinki ................................................................... 63 
9.2 
Ethical Review .............................................................................................................. 63 
9.3 
Informed Consent Process ............................................................................................ 63 
9.4 
Study Discontinuation and Closure ............................................................................... 64 
9.5 
Confidentiality and Privacy .......................................................................................... 64 
9.6 
Clinical Monitoring ....................................................................................................... 65 
9.7 
Quality Assurance and Quality Control ........................................................................ 65 
9.8 
Data Handling and Record Keeping ............................................................................. 65 
9.9 
Protocol Deviations ....................................................................................................... 66 


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9.10 
Publication Policy ......................................................................................................... 66 
10 
REFERENCES .............................................................................................................. 67 
APPENDIX A: Diagnostic Criteria for Atopic Dermatitis ........................................................... 69 
APPENDIX B: Eczema Area and Severity Index ........................................................................ 70 
APPENDIX C: vIGA-ADTM ......................................................................................................... 71 
APPENDIX D: Scoring Atopic Dermatitis - SCORAD ............................................................... 72 
APPENDIX E: Patient-Oriented Eczema Measure ...................................................................... 73 
APPENDIX F: Patient-Oriented Eczema Measure ....................................................................... 74 
APPENDIX G: Dermatology Life Quality Index ......................................................................... 75 
 
LIST OF TABLES 
 
Table 1: Schedule of Events ......................................................................................................... 23 
Table 2. Study Products ................................................................................................................ 40 
Table 3. Prohibited Therapies or Procedures ................................................................................ 45 
Table 4. Examples of H2 antagonists and Proton Pump Inhibitors .............................................. 46 
Table 5: Clinical Laboratory Testing ............................................................................................ 51 
 
LIST OF FIGURES 
 
Figure 1: Study Diagram ............................................................................................................... 22 
Figure 2: Pruritus Numeric Rating Scale ...................................................................................... 48 
 
 
 
 
 




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-To detail how subjects who start to 
use prohibited medications for AD 
during the study will be handled. 
 
 
 
 
 
 
 
 
-To remove the exclusion of certain 
body parts for the BSA calculation. 
 
 
 
-To correct typographical errors. 
 
-Synopsis, Schedule of event (footnote), 
Sections 5.3.1, 6.4.2, 8.3.1 and 8.3.2, to 
specify 
how 
subjects 
who 
start 
medication for AD during the study are 
handled 
and 
if 
study 
product 
discontinuation is required or not. 
Specifications with regards to how to 
handle missing data in the statistical 
analysis have been made in the statistical 
sections.  
 
-Section 7.1.4, the following "([excluding 
palms, back of the hands, soles, scalp, 
genitals, and folds])" was removed as it 
was included in the protocol in error.  
 
-Synopsis, secondary pharmacokinetic 
endpoint revised to be consistent with 
section 3.  
-Section 5.2, criterion # 16, bullet 
numbering corrected to be consistent with 
the numbering in the synopsis.  
-Section 5.2, criterion # 37 (in version 
1.0), revised to be consistent with 
criterion in the synopsis. 
-Section 9.10, section title was corrected.  
-Minor typographical errors corrected 
throughout the document.  
3.0 / 07 February 
2019 
- To revise the inclusion criterion 
related to body mass index (BMI) in 
order to allow wider pool of subjects 
access to the trial. 
- Synopsis and Section 5.1, inclusion 
criterion #7, BMI was revised to ≤ 38 
kg/m2. 
 
 
 


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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP), the Declaration of Helsinki, and applicable 
local regulations. The principal investigator will assure that no planned deviation from, or changes 
to the protocol will take place without prior agreement from the sponsor and documented approval 
from the institutional review board (IRB) / ethic committee (EC), except where necessary to 
eliminate an immediate hazard(s) to the trial subjects. All personnel involved in the conduct of this 
study have completed ICH GCP training. 
 
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IRB/EC for review and approval. Approval of both the protocol and the consent 
form must be obtained before any subject is enrolled. Any amendment to the protocol will require 
review and approval by the IRB/EC before the changes are implemented to the study. All changes 
to the consent form will be IRB/EC approved. 




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PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
Investigator Name: 
 
 
 
Signature: 
 
Date: 
 
 
 
 
 
 
(DD-MMM-YYYY) 
 
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/independent ethics committee procedures, instructions from sponsor’s representatives, 
the Declaration of Helsinki, ICH GCP guidelines, applicable Canadian regulations, applicable 
European regulations, applicable United States federal regulations, and local regulations 
governing the conduct of clinical studies. 
 
 
 
 


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LIST OF ABBREVIATIONS 
AD 
atopic dermatitis 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANCOVA 
analysis of covariance 
anti-HBc 
antibody to hepatitis B core antigen 
AST 
aspartate aminotransferase 
β-hCG 
β-human chorionic gonadotropin 
BMI 
body mass index 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CK 
creatine kinase 
CMH 
Cochran Mantel Hansel 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form 
CRP 
C-reactive protein 
CPK 
creatine phosphokinase 
CRO 
contract research organization 
CV 
coefficient of variation 
DSMB 
Data and Safety Monitoring Board  
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
EC 
ethic committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ET 
early termination 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GERD  
Gastroesophageal reflux disease 
GGT 
gamma-glutamyl-transferase 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCT 
hematocrit 
HCV 
hepatitis C virus 
HDL  
high-density lipoproteins 
Hgb 
hemoglobin 
HIV 
human immunodeficiency virus 
IB 
investigator brochure  
ICH 
International Council for Harmonisation 
IGA 
Investigator Global Assessment 
IRB 
institutional review board 
ITT 
intent-to-treat (population) 


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IWRS 
Interactive Web Response System 
LDH 
lactate dehydrogenase 
LDL  
low-density lipoproteins 
LMW 
low molecular weight  
JAK 
janus kinase 
Mapi 
Mapi Life Sciences 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA  
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed Model Repeated Measures 
MPV 
mean platelet volume 
NRS 
numeric rating scale 
NSAID 
nonsteroidal anti-inflammatory drug 
NYHA 
New York Heart Association  
OLE 
open label extension study 
PD 
pharmacodynamic 
PK 
pharmacokinetic  
PLT 
platelets 
POEM 
Patient-Oriented Eczema Measure 
PP 
per-protocol (population)  
PPD 
purified protein derivative  
PUVA 
psoralen-UV-A 
QC 
quality control 
RBC 
red blood cell (count) 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAF 
safety (population) 
SAP 
statistical analysis plan 
SCORAD 
SCORing Atopic Dermatitis 
SD 
standard deviation 
SYK 
spleen tyrosine kinase 
TB 
tuberculosis  
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
UV 
ultraviolet 
VTE 
venous thromboembolic event 
WBC 
white blood cell (count) 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 
 
 


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1 
PROTOCOL SUMMARY 
1.1 Synopsis 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
Title of Study:  
A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study to Evaluate the Efficacy, Safety, 
Tolerability, and Pharmacokinetics of ASN002 in Subjects with Moderate to Severe Atopic Dermatitis 
Phase of Development:  
Phase 2b 
Study Center(s):  
Approximately 50 study centers located in the United States, Canada, and Germany will participate in 
this study. 
Number of Subjects (planned):  
Approximately 220 subjects will be included in this study to reach 160 evaluable subjects. 
Duration of Study:  
The maximum study duration per subject is up to 20 weeks (including up to 4 weeks for the screening 
period, up to 12 weeks for the treatment period, and up to 4 weeks for the follow-up period).  
Investigational Product, Dosage, and Mode of Administration:  
ASN002 40, 60, or 80 mg or placebo orally administered once daily for 12 weeks. ASN002 will be 
available in 20-mg strength tablets. 
Subjects will be randomized in a 1:1:1:1 ratio. Randomization will be stratified by baseline disease 
severity ([Eczema Area and Severity Index (EASI) = 16.0-21.2] vs. [EASI =21.3-29.9] vs. 
[EASI = ≥ 30.0]) and biopsy collection.   
Objectives: 
Primary: 
• 
To evaluate the efficacy of ASN002 in subjects with moderate to severe atopic dermatitis (AD) 
Secondary: 
• 
To evaluate the safety and tolerability of ASN002 in subjects with moderate to severe AD 
• 
To evaluate the pharmacokinetic (PK) profile of ASN002 in subjects with moderate to severe AD 
Exploratory: 
• 
To assess population PK of ASN002 in AD subjects via a population PK analysis approach 
• 
To evaluate pharmacodynamic (PD) and biomarkers for evidence of drug activity in subjects with 
moderate to severe AD 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
• 
To explore the relationships between PK exposure and clinical measurement (e.g., biomarker, 
efficacy, and safety) as appropriate  
Endpoints: 
Primary Endpoint: 
• 
Change from baseline in EASI score at Week 12 
Secondary Endpoints: 
Secondary efficacy endpoints include: 
• Change from baseline in EASI score at Weeks 2, 4, and 8 
• Percent change from baseline in EASI score at Weeks 2, 4, 8, and 12 
• Proportion of subjects with at least a 50% reduction from baseline in EASI (EASI50) at Weeks 2, 
4, 8, and 12 
• Proportion of subjects achieving at least a 75% reduction from baseline in EASI (EASI75) at 
Weeks 2, 4, 8, and 12 
• Proportion of subjects achieving at least a 90% reduction from baseline in EASI (EASI90) at 
Weeks 2, 4, 8, and 12 
• Time to achieve EASI50, EASI75, and EASI90 relative to baseline. 
• Proportion of subjects achieving at least a 2-grade reduction from baseline to clear (0) or almost 
clear (1) in Investigator’s Global Assessment (IGA) at Weeks 2, 4, 8, and 12 
• Proportion of subjects achieving at least a 2-grade reduction from baseline in IGA at Weeks 2, 4, 
8, and 12 
• Proportion of subjects achieving an IGA of clear (0) or almost clear (1) at Weeks 2, 4, 8, and 12 
• Change from baseline in SCORing Atopic Dermatitis (SCORAD) at Weeks 2, 4, 8, and 12 
• Change from baseline in 5-D Pruritus Scale at Weeks 2, 4, 8, and 12 
• Change and percent change from baseline in single daily timepoint pruritus Numeric Rating Scale 
(NRS) at Week 1 
• Change and percent change from baseline in weekly average of the peak daily pruritus NRS at 
Weeks 1, 2, 4, 8, and 12  
• Proportion of subjects achieving at least a 4-point reduction from baseline in weekly average of 
the peak daily pruritus NRS at Weeks 1, 2, 4, 8, and 12 
• Change and percent change from baseline in Body Surface Area (BSA) involved with AD at 
Weeks 2, 4, 8, and 12 
• Change from baseline in Patient-Oriented Eczema Measure (POEM) at Weeks 2, 4, 8, and 12 
• Change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 2, 4, 8, and 12 
Secondary safety endpoints include: 
• Number of treatment-emergent adverse events (TEAEs)  
• Number of drug-related TEAEs  
• Proportion of subjects withdrawing from worsening AD at Weeks 2, 4, 8, and 12 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
• Changes in vital signs, physical examinations, electrocardiogram (ECG), and safety laboratory 
tests  
Secondary pharmacokinetic endpoint includes: 
• Measurement of plasma concentrations of ASN002 in all subjects receiving ASN002 treatment 
Exploratory Endpoints: 
Exploratory endpoints include: 
• Change from baseline in expression levels and kinase activity of key disease pathways in skin 
biopsies, such as Th2 and other T helper cell axes 
• Changes from baseline in cellular infiltrates of T-cells and dendritic cells 
• Changes from baseline in epidermal hyperplasia measures (epidermal thickness, ki67, and K16 
expression) 
• Changes from baseline in mRNA and protein expression of differentiation markers 
• Changes in inflammatory measures in peripheral blood using proteomics 
• Characterization of population PK parameters via nonlinear mixed-effects modeling 
• Changes from baseline in clinical safety, efficacy, and biomarker measurements in relationship to 
PK exposure  


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
Study Design: 
Approximately 220 subjects with moderate to severe AD (as defined by a BSA involved with AD of 
≥ 10%, an EASI ≥ 16, and an IGA ≥ 3 at Day 1) will be included in this randomized, double-blind, 
placebo-controlled, multicenter, Phase 2b study.  
All subjects will sign an informed consent and undergo screening for study eligibility. After a screening 
period of no more than 30 days (from Day -30 to Day -1), eligible subjects will be randomized (1:1:1:1) 
on Day 1 to receive ASN002 at 40 mg, 60 mg, or 80 mg, or placebo once daily for 12 weeks, followed 
by a 4-week follow up period for subjects not participating in the open label extension (OLE) study. For 
scheduled study visits, subjects will come to the study centers on seven occasions: screening; Day 1; 
Weeks 2, 4, 8, and 12; and Week 16/early termination (ET) for subjects not participating in the OLE 
study. 
Efficacy will be assessed using IGA, EASI, SCORAD, BSA, pruritus NRS (daily), and 5-D pruritus 
scale. Quality of life will be evaluated using POEM and DLQI.  
Safety will be assessed by adverse events (AEs), physical examination, vital signs, 12-lead ECG, and 
clinical laboratory tests. 
Pre- and post-dose PK blood samples will be collected from all subjects on a sparse sampling schedule 
on Day 1 and Weeks 2, 4, 8 and 12 (or ET visit, if applicable).  
At selected study centers, in a subset of approximately 68 subjects who consent, PD blood samples will 
be collected pre-dose on Day 1 and Week 12 (or ET visit, if applicable). PD samples will be obtained 
from the same subjects who consent to biopsy collection. An additional PD blood sample will be 
collected at Week 4 in subjects who also consent to four skin biopsies. 
At selected study centers, in a subset of approximately 68 subjects who consent, three or four skin 
biopsies will be collected during this study. Two 4.5-mm punch biopsies (one from lesional skin and one 
from adjacent nonlesional skin) will be collected at Day 1, and one 4.5-mm punch biopsy will be 
collected from the same lesional skin (outside the scar of the previous biopsy, at least 1 cm away from 
the previous scar) at Week 12 (or ET visit, if applicable). In addition, one 4.5-mm punch biopsy will be 
collected from the same lesional skin (outside the scar of the previous biopsy, at least 1 cm away from 
the previous scar) at Week 4 in subjects who consent to four skin biopsies. 
At selected study centers, in a subset of approximately 68 subjects who consent, medical photographs of 
the area of worst AD involvement will be taken to illustrate any visible clinical change.  
Inclusion/Exclusion Criteria: 
Inclusion criteria: 
1. Male or female subject, aged 18 to 75 years, inclusive, at the time of consent. 
2. Subject has clinically confirmed diagnosis of active atopic dermatitis, according to Hanifin and 
Rajka criteria. 
3. Subject has at least a 6-month history of atopic dermatitis and had no significant flares in atopic 
dermatitis for at least 4 weeks before screening (information obtained from medical chart or subject’s 
physician, or directly from the subject). 
4. Subject has an EASI score ≥ 16 at Day 1. 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
5. Subject has moderate to severe atopic dermatitis at Day 1, as defined by an IGA ≥ 3. 
6. Subject has atopic dermatitis covering ≥ 10% of the BSA on Day 1. 
7. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
8. Subject has a history of inadequate response to topical corticosteroids or calcineurin inhibitors as 
treatment for AD within 1 year before the screening visit (information obtained from medical chart 
or subject history). 
9. Subject has been using an emollient (except those containing urea) either once daily or twice daily 
for at least 1 week prior to Day 1 and agrees to continue using that same emollient, daily and at the 
same frequency, throughout the study. Note: On the day of scheduled visits, subjects cannot apply 
emollient before their scheduled visit time.   
10. For women of childbearing potential involved in any sexual intercourse that could lead to pregnancy: 
the subject must agree to use a highly effective contraceptive method from at least 4 weeks before 
Day 1 until at least 4 weeks after the last study product administration. Highly effective contraceptive 
methods include hormonal contraceptives (combined oral contraceptive, patch, vaginal ring, 
injectable, or implant), intrauterine devices or intrauterine systems, vasectomized partner(s), tubal 
ligation, or double barrier methods of contraception (barrier methods include male condom, female 
condom, cervical cap, diaphragm, contraceptive sponge) in conjunction with spermicide.  
Note: Subjects must have been on a stable dose of hormonal contraceptives for at least 4 weeks 
before Day 1.  
Note: The above list of contraceptive methods does not apply to subjects who are abstinent for at 
least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal intercourse 
throughout the study.  The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the participant. 
Note: For countries where double barrier methods are not accepted as highly effective contraception, 
then this option must not be considered. 
Note: A woman of nonchildbearing potential is as follows:  
a. Woman who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy); 
b. Woman who has had a cessation of menses for at least 12 months without an alternative 
medical cause, and a follicle-stimulating hormone (FSH) test confirming nonchildbearing 
potential (refer to laboratory reference ranges for confirmatory levels).  
11. For men involved in any sexual intercourse that could lead to pregnancy, subject must agree to use 
one of the highly effective contraceptive methods listed in Inclusion Criterion #10, from Day 1 until 
at least 4 weeks after the last study product administration. If the female partner of a male subject 
use any of the hormonal contraceptives method listed above, this contraceptive method must be used 
by the female partner from at least 4 weeks before Day 1 until at least 4 weeks after the last study 
product administration. 
12. Female of childbearing potential has had a negative serum pregnancy test at screening and negative 
urine pregnancy test on Day 1.  
13. Subject is willing to participate and is capable of giving informed consent. Note: Consent must be 
obtained prior to any study-related procedures. 
14. Subjects must be willing to comply with all study procedures and must be available for the duration 
of the study. 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
Exclusion criteria: 
 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during 
the study. 
2. Subject has clinically infected atopic dermatitis. 
3. Subject has a history of skin disease or presence of skin condition that, in the opinion of the 
investigator, would interfere with the study assessments.  
4. Active infection, including skin infection, requiring treatment. 
5. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Subjects 
with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or 
localized carcinoma in situ of the cervix are not to be excluded. 
6. Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs 
abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere 
with interpretation of study results. 
7. Subject has 12-lead ECG abnormalities considered by the investigator to be clinically significant or 
QTc F ≥ 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be 
confirmed with one repeat assessment. For subjects with QTcF≥450 msec on initial ECG, the mean 
of the two QTc F assessments will determine eligibility. 
8. Subject has a history of congestive heart failure New York Heart Association (NYHA) class III or 
IV. 
9. Subject has a history of erythrodermic, refractory or unstable skin disease, including AD, that 
requires frequent hospitalizations and/or frequent intravenous treatment for skin infections over the 
last year 
10. Subject has a history of eczema herpeticum within 12 months, and/or a history of 2 or more episodes 
of eczema herpeticum in the past. 
11. Subject has a history of recurrent venous thromboembolic event (VTE) (>=2) 
12. Subject has experienced any of the following within the last 6 months prior to Day 1: VTE 
myocardial infarction, angioplasty, or cardiac stent placement, unstable ischemic heart disease, or 
stroke. 
13. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned during 
the study. 
14. Subject is known to have immune deficiency or is immunocompromised. 
15. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core 
antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) at the 
screening visit. 
16. Presence of any of the following laboratory abnormalities at the screening visit: 
a. Hemoglobin < 11 g/dL; 
b. White blood cell (WBC) < 3.0 x 103 /μL; 
c. Platelet count < 125 x 103 /μL; 
d. Neutrophils < 1.8 x 103 /μL; 
e. Lymphocytes < 1.0 x 103 /μL; 
f. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 x the upper 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
limit of normal (ULN); 
g. Total bilirubin > 1.2 x ULN (except for elevated indirect bilirubin secondary to Gilbert’s 
syndrome); 
h. Creatinine > ULN. 
17. Subjects has uncontrolled hypertension within the last 1 month prior to screening or blood pressure 
at screening of systolic blood pressure >160 mm Hg or diastolic BP >95 mm Hg, confirmed by one 
repeat assessment. 
18. Subject has a known active tuberculosis or a positive tuberculosis (TB) infection test. Subject will 
be evaluated for latent TB infection with a purified protein derivative (PPD) test or a QuantiFERON-
TB Gold test. Subjects who demonstrate evidence of latent TB infection (either PPD ≥5 mm of 
induration or positive QuantiFERON-TB Gold test, irrespective of bacille Calmette-Guérin 
vaccination status) will only be allowed to participate in the study if there is documented evidence 
of a completed adequate treatment course for latent TB (with negative chest x-ray findings for active 
TB). 
19. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
20. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 
21. Subject has a known history of diverticulitis. 
22. Subject has uncontrolled diabetes. 
23. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor’s 
medical monitor, would place the subject at risk, interfere with participation in the study, or interfere 
with the interpretation of study results. 
24. Subject has used dupilumab within 12 weeks prior to Day 1.  
25. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser within 
4 weeks prior to Day 1. 
26. Subject has had psoralen-UV-A (PUVA) treatment within 4 weeks prior to Day 1. 
27. Subject has used doxepin within 1 week prior to Day 1. 
28. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
29. Subject has used topical products containing urea within 1 week prior to Day 1. 
30. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior to 
Day 1. 
31. Subject has used any topical medicated treatment for atopic dermatitis within 2 weeks prior to Day 1, 
including, but not limited to, topical corticosteroids, crisaborole and any other topical 
phosphodiesterase-4 inhibitor, calcineurin inhibitors, tars, bleach, antimicrobials, medical devices, 
and bleach baths. 
32. Subject has used systemic treatments (other than biologics) that could affect atopic dermatitis less 
than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, methotrexate, cyclosporine, 
hydroxycarbamide [hydroxyurea], azathioprine, oral/injectable corticosteroids). Note: Intranasal 
corticosteroids, eye drops containing corticosteroids, and inhaled corticosteroids for stable medical 
conditions are allowed.  
33. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half-
lives (whichever is longer) prior to Day 1. 


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Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
34. Subject is currently receiving any other medication for AD. 
35. Subject is currently receiving a nonbiological investigational product or device or has received one 
within 4 weeks prior to Day 1. 
36. Subject has excessive sun exposure, is planning a trip to a sunny climate, or has used tanning booths 
within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial sunlight exposure 
during the study. Use of sunscreen products and protective apparel are recommended when exposure 
cannot be avoided. 
37. Subject has received a live attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a 
live attenuated vaccine during the study and up to 4 weeks or 5 half-lives (of the study product), 
whichever is longer, after the last study product administration.  
38. Subject has used ASN002. 
39. Subject had prior treatment with a systemic SYK or JAK inhibitor for which the subject received no 
clinical benefit in the opinion of the investigator, or the subject relapsed whilst on therapy, or was 
withdrawn for safety reasons. 
40. Subject has a known hypersensitivity to ASN002 or its excipients. 
41. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to 
Day 1. 
42. Subject has a close affiliation with the investigator (e.g., a close relative) including any study staff 
of the sites or persons working at the CRO, or subject is an employee of the sponsor. 
43. Subject is institutionalized because of legal or regulatory order. 
44. Only for subjects consenting to biopsies: 
a. Subject has a history of an allergic reaction or significant sensitivity to lidocaine or other 
local anesthetics; 
b. Subject has a history of hypertrophic scarring or keloid formation in scars or suture sites; 
c. Subject is taking anticoagulant medication, such as heparin, low molecular weight 
(LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin which will be allowed), 
within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. Nonsteroidal anti-
inflammatory drugs [NSAIDs] will not be considered antiplatelets and will be allowed. 
Statistical methods:  
Continuous variables will be summarized in tables and will include the number of subjects, mean, 
standard deviation (SD), percent of coefficient of variance (CV%), median, minimum, and maximum. 
Categorical variables will be presented in tables as frequencies and percentages. A statistical analysis 
plan (SAP) will provide additional details on the approach to the analysis and data displays. 
Efficacy Analyses: 
The primary efficacy endpoint will be analyzed using a repeated measures analysis of covariance on 
change-from-baseline variable to compare the time profile between treatments where the visit will be the 
time factor; and the stratification factors, treatment group, and interaction term for treatment-by-visit 
will be the fixed effects and the baseline value will be the covariate. An unstructured variance-covariance 
matrix will be used.  
For categorical efficacy endpoints involving proportions of IGA, EASI and NRS (e.g. the proportion of 
subjects achieving at least a 2-grade reduction from baseline to clear (0) or almost clear (1) in IGA at 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
week 12), a Cochran Mantel Hansel test (CMH) controlling for the stratification variables will be 
performed. 
 
For the primary endpoint of change-from-baseline in EASI at Week 12, a Bonferroni adjustment will be 
done to test the three comparisons of interest (40 mg vs. Placebo, 60 mg vs. Placebo and 80 mg vs. 
Placebo) at nominal alpha of 0.0167.  
Safety Analyses: 
The safety analysis will include reported AEs and other safety information (i.e., clinical laboratory 
evaluations, vital signs, physical examination, and 12-lead ECG results). A summary of safety results 
will be presented for each treatment group. 
PK Analyses: 
ASN002 concentration data will be summarized based on nominal timepoints using descriptive statistics, 
such as mean, SD, CV%, median, minimum and maximum.  
Population PK analysis will be performed using nonlinear mixed-effects modeling approach with first-
order conditional methods. This analysis may be combined with PK concentrations from other clinical 
trials in healthy and AD subjects as appropriate.  
PD Analyses: 
Biomarker levels will be compared to placebo adjusted change from baseline over time for each 
treatment group, and the parameters will be summarized by treatment group and overall using descriptive 
statistics.  
PK/PD Analyses: 
PK-efficacy, PK-safety and PK-biomarkers relationships will be explored using linear regression, loess 
plots, Hills functions, or logistic regression, as appropriate. 
Sample Size Consideration: 
Using the following assumptions: a change-from-baseline in EASI at week 12 of at least -15 in the 
ASN002 dosing groups, a change-from-baseline of -8 in the placebo group, a common standard-
deviation of 8, alpha of 0.0167 for each comparison of interest, we would need 40 subjects per group in 
order to achieve a power of 92% on the primary efficacy endpoint.  
 
Moreover, with 46 subjects per group, we would have 80% power to show a statistically significant 
difference between the higher dosing group and placebo in IGA responses (one of the key secondary 
efficacy endpoint), assuming a response of 37.5% vs. 11.1% in the higher dosing and placebo groups, 
respectively, using an alpha of 5%.   
 
Thus, assuming about 15% dropout rate, 55 subjects per group will need to be enrolled in this trial for a 
total of 220 subjects in order to have a minimum of 46 subjects per group to evaluate efficacy with 
adequate power. 
 


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1.2 Study Diagram 
Figure 1: Study Diagram 
 
1.3 Schedule of Events 
The 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. The Day 1 visit must be performed, at the latest, 
30 days after the screening visit. The screening evaluation will be performed according to the 
inclusion and exclusion criteria. If the subject fulfills all inclusion criteria and no exclusion criteria, 
he or she may be included in the study.  
 
Table 1 provides a description of the procedures to be performed at each visit. 
 
If assessments are scheduled at the same time, then the assessments should occur in the following 
order: 
• Vital signs (within 1 hour of dosing)     
• 12-lead ECG  
• Blood draws for PK and PD samples (time window vs drug administration detailed in footer 
of  Table 1) 
 






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2 
INTRODUCTION 
2.1 Background 
 Atopic Dermatitis 
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Inflammation, pruritus, papules, 
lichenification, excoriations, xerosis and oozing clinically characterize AD.(1) Onset typically 
occurs in children and can improve in adulthood, however, late onset can also occur.(2) Atopic 
dermatitis affects 10-20% of children and 1-3% of adults.(2, 3) Moreover, recent studies suggest 
that the prevalence of AD in adults could be much higher.(4). Prevalence has also been observed 
to be higher in industrialized countries, suggesting, at least partially, an environmental link.(5) The 
quality of life and psychological state of patients with AD, as well as the parents of patients can 
be greatly impacted by this disease.(6, 7)  Pruritus prevalence in AD patients is greater than 80% 
and greatly impairs their quality of life by causing sleep and psychological disturbance.(8) 
 
It is a heterogeneous disease with a wide spectrum of clinical phenotype and a complex 
pathophysiology.(9, 10) The precise etiology of AD remains unclear but is likely to be 
multifactorial in nature, involving genetics, abnormalities in the skin barrier, immune system 
defects, and environmental triggers (e.g., allergens, irritants, microbes, diet, stress, air quality).(3, 
11)   
 
In recent years, the understanding of the clinical characterization of AD phenotypes and molecular 
mechanisms of the disease has advanced greatly giving hope for the development of new 
therapeutic agents.(5, 10, 12, 13) Janus kinase (JAK) and Spleen tyrosine kinase (SYK) are 
tyrosine kinases that have been shown to be implicated in the pathogenesis of various types of 
autoimmune and inflammatory diseases.(14, 15) It is understood that AD is primarily a T cell-
driven disease.(16) Atopic dermatitis was shown to have a strong Th2 response where IL-4 
promotes the differentiation of Th2 cells, which are regulated by the JAK signaling pathway. 
Moreover, activation of SYK leads to the release of various inflammatory mediators and plays a 
role in downstream signaling involved in the pathology of several allergic and autoimmune 
diseases.(14, 17) Therefore, targeting both JAK and SYK kinases may provide a new therapeutic 
approach in the treatment of inflammatory disorders, such as atopic dermatitis.  
 ASN002 in Atopic Dermatitis 
ASN002 is an orally bioavailable, potent dual inhibitor of JAK and SYK kinases with 50% 
inhibitory concentrations (IC50 values) of 5-46 nM in biochemical assays. In cell-based 
mechanistic assays, the compound showed inhibition of IgE-immune complex induced 
degranulation and phosphorylation of LAT (Linker for Activation of T cells) a substrate of SYK, 
and also IL-6 induced phosphorylation of STAT3 (IC50 range 14–143 nM). In a collagen-
induced arthritis model, ASN002 demonstrated a significant reduction in arthritic, 
histopathology and radiographic scores when compared to vehicle. The compound also showed 
broad antiproliferative activity in a panel of cell lines representing both solid and 
leukemia/lymphoma tumor types. The data from both in vitro (cell line) and in vivo efficacy 


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studies with ASN002 provide strong rationale for its evaluation in subjects with atopic 
dermatitis. In a Phase 1b study (ASN002AD-101), plasma concentrations of ASN002 were 
measured in subjects with atopic dermatitis following single and repeated once daily oral 
administration at 20, 40 and 80 mg. At steady state, Cmax and AUC were dose dependent with 
approximately 1.5-fold or less accumulation compared to those on Day 1, and the mean 
elimination t1/2 were 7.3-13.7 hours. At 80 mg, the mean Cmax and AUCtau of ASN002 at steady 
state were 252 ng/ml and 3340 ng*hr/ml, respectively.  The safety and tolerability profile of 
ASN002 at all dose levels was excellent. The most common adverse event (AE) observed was 
transient, mild headache, mostly restricted to Day 1 likely due to fasting. There were no 
clinically significant laboratory changes including hematological parameters observed in this 
study. ASN002 showed robust clinical efficacy with nearly all patients obtaining a 50% 
improvement in disease severity (EASI50) at 40 mg and 80 mg once daily and substantial 
decreases in patient-reported itch measured by Numeric Rating Scale (NRS) after 4 weeks of 
treatment.  
 Study Rationale  
In the previous clinical trial (ASN002AD-101), ASN002 has showed significant benefit for the 
treatment of atopic dermatitis, especially at 40 and 80 mg once-daily dosing regimens. This trial 
is to further investigate the benefit and risk of ASN002 in subjects with atopic dermatitis for a 12-
week treatment duration. 
 
Current therapies for AD provide relief of symptoms for most but not all patients. Additionally, 
they do not prevent or eradicate the disease. The development of medications that precisely target 
the molecular mediators of inflammation involved in AD is certainly a promising approach to treat 
this disease. There is definitely a need for new treatments in AD in order to increase the existing 
options available to clinicians. 
 
The primary objective of this study is to assess the efficacy of ASN002 in subjects with moderate-
to-severe atopic dermatitis. Safety and tolerability of ASN002 will also be evaluated as secondary 
endpoint as well as its pharmacokinetic profile. The doses to be administered in this study range 
between 40 and 80 mg, which were found to be well tolerated and safe in a previous Phase I study. 
Adverse events (AEs) observed in the Phase I study were of mild or moderate intensity following 
80 mg dose.  One SAE was reported (anxiety attack), which was not related to the study drug, and 
one event led to treatment discontinuation for one subject (hypertension) in the 80-mg cohort (refer 
to section 2.2.1 for more details). Once daily administration was chosen based on the data from 
the clinical studies in oncology subjects and healthy volunteers. Pharmacokinetic analyses indicate 
sufficient systemic exposure for ASN002 efficacy and a half-life of ~10 hours is adequate for 
maintaining target trough concentrations. 
2.2 Risk/Benefit Assessment 
 Known Potential Risks 
The data from both nonclinical and clinical studies with ASN002 suggest that it is safe and well-
tolerated at the doses to be administered in the present study.  


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In cancer subjects, ASN002 has been well tolerated. The most common reported AEs were anemia, 
fatigue, chills, dizziness and diarrhea, as expected in heavily pretreated and refractory cancer 
patients. 
 
The safety of ASN002 have also been studied in a safety, tolerability, PK and food effect study in 
healthy subjects at doses up to 100 mg following a single oral administration. The most common 
adverse event in this study was headache. One SAE, premature ventricular contractions, which 
were asymptomatic and mild, was experienced by one subject dosed with 50 mg ASN002 once. 
These resolved over 5 days without sequelae. This event was considered possibly related to study 
medication and unexpected. 
 
The safety of ASN002 was also assessed in a previous Phase I study in AD patients. Adverse 
events (AEs) observed in the Phase I study were mild or moderate at doses up to 80 mg.  There 
were no drug-related SAEs reported in this study. One SAE was reported (anxiety attack), which 
was not related to the study drug. In addition, one event led to treatment discontinuation for one 
subject (hypertension) in the 80-mg cohort. The corresponding patient was also on Ritalin and was 
observed with fluctuating blood pressure measurement results even after clearance of the study 
drug suggesting Stage 1 hypertension levels. It is also important to note that the patient also had 
borderline high level of blood pressure at baseline. Considering the above, this study suggests that 
ASN002 is safe and well-tolerated at doses up to 80 mg.  
 
Further information related to previous clinical studies is available in the Investigator Brochure. 
 Known Potential Benefits 
It is anticipated that subjects will see an improvement in their atopic dermatitis condition as a result 
of participating in this study, if they are randomized to active investigational product. Participation 
in this study may help generate future benefit for larger groups of patients with atopic dermatitis. 
 Assessment of Risks and Benefits 
All quality, pharmacology and toxicology data, and satisfactory safety and tolerability data 
demonstrated in nonclinical and previous clinical studies are considered sufficient to expect a 
positive benefit/risk ratio for the treatment of atopic dermatitis with ASN002, and therefore to 
initiate this study. 
 
The risk to subjects in this trial will be minimized by compliance with the eligibility criteria, proper 
study design, and close monitoring. 
 
 
 






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4 
STUDY DESIGN  
4.1 Overall Design  
This study will be performed at approximately 50 study centers located in the United States, 
Canada and Germany. 
 
This study is a randomized, double-blind, placebo-controlled, multicenter, Phase 2b study. 
Approximately 220 subjects with moderate to severe AD (as defined by a BSA involved with AD 
of ≥ 10%, an EASI ≥ 16, and an IGA ≥ 3 at Day 1) will be included in this study to complete the 
study with at least 160 evaluable subjects. Subjects will be men or women, aged 18 to 75 years, 
inclusive, at the time of consent.  
 
Each subject should read and sign an informed consent form prior to any screening procedures 
being performed. Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria 
will be accepted into the study. After a screening period of no more than 30 days (from Day -30 
to Day -1), eligible subjects will be randomized (1:1:1:1) on Day 1 to receive ASN002 at 40 mg, 
60 mg, or 80 mg, or placebo once daily for 12 weeks. The treatment period will be followed by a 
4-week follow-up period for subjects not participating in the open label extension (OLE) study.  
For scheduled study visits, subjects will come to the study centers on seven occasions: screening, 
Day 1, Weeks 2, 4, 8, and 12, and Week 16/ ET for subjects not participating in the OLE study. 
 
Efficacy will be assessed by IGA, EASI, SCORAD, BSA, pruritus NRS (daily), and 5-D pruritus 
scale. Quality of life will be evaluated using POEM and DLQI.  
 
Safety will be assessed by AEs, physical examination, vital signs, 12-lead ECG, and clinical 
laboratory tests. 
 
Pre- and post-dose PK blood samples will be collected from all subjects on a sparse sampling 
schedule at Day 1, and Weeks 2, 4, 8 and 12 (or ET visit, if applicable). 
 
At selected study centers, in a subset of approximately 68 subjects who consent, PD blood samples 
will be collected pre-dose on Day 1 and Week 12 (or ET visit, if applicable). PD samples will be 
obtained from the same subjects who consent to biopsy collection. An additional PD blood sample 
will be collected at Week 4 in subjects who also consent to four skin biopsies. 
 
At selected study centers, in a subset of approximately 68 subjects who consent, three or four skin 
biopsies will be collected during this study. Two 4.5-mm punch biopsies (one from lesional skin 
and one from adjacent nonlesional skin) will be collected at Day 1, and one 4.5-mm punch biopsy 
will be collected from the same lesional skin (outside the scar of the previous biopsy, at least 1 cm 
away from the previous scar) at Week 12 (or ET visit, if applicable). In addition, one 4.5-mm 
punch biopsy will be collected from the same lesional skin (outside the scar of the previous biopsy, 
at least 1 cm away from the previous scar) at Week 4 in subjects who consent to four skin biopsies. 
 


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At selected study centers, in a subset of approximately 68 subjects who consent, medical 
photographs of the area of worst AD involvement will be taken to illustrate any visible clinical 
change.  
 
No formal interim analyses are planned for this study.  However, unblinded safety data will be 
generated and reviewed by a Data and Safety Monitoring Board (DSMB) during the study.  
4.2 Scientific Rationale for Study Design  
The proposed design is considered appropriate for assessing the efficacy of ASN002 study 
products compared to a placebo in subjects with AD, and to evaluate the safety and tolerability of 
ASN002 study product in subjects with atopic dermatitis. 
 
The study will be randomized to ensure random allocation of subjects to treatment arms to reduce 
bias. Because efficacy assessments of AD have a high degree of subjectivity, the study will be 
double-blinded. The highest degree of subjects and assessor blinding should be sought to achieve 
credible inference. It is also important to have a placebo control in a Phase 2 study to control for 
confounding factors, such as potential investigator bias, and to ensure that the statistical procedures 
can be appropriately applied.  
4.3 End of Study Definition 
A subject is considered to have completed the study if he or she has completed all phases of the 
study, including the last visit or the last scheduled procedure shown in the schedule of events, 
Table 1. 
4.4 Safety 
Monitoring 
Criteria 
for 
Individual 
Subject 
Treatment 
Interruption/Discontinuation 
In the event of an adverse event or laboratory abnormality, individual subject study treatment may 
be temporary or permanently discontinued based on the Investigator’s judgement in accordance 
with the guidelines described in this section.  
 
Treatment may be resumed upon recovery to baseline or mild levels after the condition leading to 
suspension of dosing resolves, at the discretion of the principal investigator in consultation with 
the medical monitor.  A decision to temporarily discontinue study drug and/or to reinstitute study 
treatment should be discussed with the medical monitor.  The investigator may suspend study 
treatment at any time, even without consultation with the medical monitor if the urgency of the 
situation requires immediate action and if this is determined to be in the subject’s best 
interest.  However, the medical monitor should be contacted as soon as possible in any case of 
study drug discontinuation/interruption.  Resumption of study treatment after temporary 
discontinuation should always be discussed with the medical monitor. 
 
Any retreatment should only be considered upon written agreement between the investigator and 
the sponsor. This information pertaining to discontinuation or interruption of study medication and 
the reasons for it must be recorded in the case report form. 


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No dose reductions or modifications are permitted. 
 Interruption criteria 
A subject who meets either of the below criteria will have the study drug interrupted until 
laboratory retesting is performed and/or event resolution.  
 
• neutrophils > 0.5 x 103 /μL but < 1 x 103 /μL; 
• platelet count > 50 x 103 /μL but < 100 x 103 /μL; 
• lymphocytes < 0.5 x 103 /μL but > 0.2 x 103 /μL; 
• CPK >10 x ULN; 
• an infection requiring IV treatment with antiviral, antibiotic, antiprotozoal, antiparasite or 
requiring oral medications of those longer than 2 weeks; 
• AST/ALT > 5 x ULN*. 
 
*Decision to restart the medication following any laboratory abnormality described above will 
be made in consultation with the study sponsor and medical monitor. 
 Permanent study discontinuation 
Adverse events or laboratory abnormalities who meet either of the below criteria will result in 
permanent study discontinuation of the subject. Treatment with the study product will be 
immediately stopped and the subject withdrawn from this study. 
 
• serious opportunistic infection such as tuberculosis;  
• hypertension that cannot be controlled with additional antihypertensive medication(s); 
• neutrophils ≤ 0.5 x 103 /μL; 
• lymphocytes ≤ 0.2 x 103 /μL; 
• platelets ≤ 50 x 103 /μL; 
• diagnosis of malignancy; 
• venous thrombo-embolic event or major cardiovascular event. 
4.5 Data and Safety Monitoring Board  
Safety oversight will be under the direction of an independent DSMB composed of individuals 
with the appropriate expertise. Members of the DSMB should be independent from the study 
conduct and free of conflict of interest, or measures should be in place to minimize perceived 
conflict of interest. The DSMB will meet at least three times during the study to assess unblinded 
safety data on each arm of the study and will provide their recommendations concerning the 
continuation, modification, or termination of the trial. 
 
 
 


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5 
STUDY POPULATION  
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, a subject must meet all of the following criteria 
at the screening and Day 1 visits, unless specified otherwise:  
1. Male or female subject, aged 18 to 75 years, inclusive, at the time of consent. 
2. Subject has clinically confirmed diagnosis of active atopic dermatitis, according to Hanifin and 
Rajka criteria (Appendix A). 
3. Subject has at least a 6-month history of atopic dermatitis and had no significant flares in atopic 
dermatitis for at least 4 weeks before screening (information obtained from medical chart or 
subject’s physician, or directly from the subject). 
4. Subject has an EASI score ≥ 16 at Day 1. 
5. Subject has moderate to severe atopic dermatitis at Day 1, as defined by an IGA ≥ 3. 
6. Subject has atopic dermatitis covering ≥ 10% of the BSA on Day 1. 
7. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
8. Subject has a history of inadequate response to topical corticosteroids or calcineurin inhibitors 
as treatment for AD within 1 year before the screening visit (information obtained from 
medical chart or subject history). 
9. Subject has been using an emollient (except those containing urea) either once daily or twice 
daily for at least 1 week prior to Day 1 and agrees to continue using that same emollient, daily 
and at the same frequency, throughout the study. Note: On the day of scheduled visits, subjects 
cannot apply emollient before their scheduled visit time.   
10. For women of childbearing potential involved in any sexual intercourse that could lead to 
pregnancy: the subject must agree to use a highly effective contraceptive method from at least 
4 weeks before Day 1 until at least 4 weeks after the last study product administration. Highly 
effective contraceptive methods include hormonal contraceptives (combined oral 
contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine 
systems, vasectomized partner(s), tubal ligation, or double barrier methods of contraception 
(barrier methods include male condom, female condom, cervical cap, diaphragm, and 
contraceptive sponge) in conjunction with spermicide.  
Note: Subjects must have been on a stable dose of hormonal contraceptives for at least 4 weeks 
before Day 1.  
Note: The above list of contraceptive methods does not apply to subjects who are abstinent for 
at least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal intercourse 
throughout the study.  The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the clinical trial and the preferred and usual lifestyle of the participant. 
Note: For countries where double barrier methods are not accepted as highly effective 
contraception, then this option must not be considered. 
Note: A woman of nonchildbearing potential is as follows:  


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a. 
Woman who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy); 
b. 
Woman who has had a cessation of menses for at least 12 months without an 
alternative medical cause, and a follicle-stimulating hormone (FSH) test confirming 
nonchildbearing potential (refer to laboratory reference ranges for confirmatory 
levels).  
11. For men involved in any sexual intercourse that could lead to pregnancy, subject must 
agree to use one of the highly effective contraceptive methods listed in Inclusion 
Criterion #10, from Day 1 until at least 4 weeks after the last study product administration. 
If the female partner of a male subject use any of the hormonal contraceptives methods 
listed above, this contraceptive method must be used by the female partner from at least 
4 weeks before Day 1 until at least 4 weeks after the last study product administration. 
12. Female of childbearing potential has had a negative serum pregnancy test at screening and 
negative urine pregnancy test on Day 1.  
13. Subject is willing to participate and is capable of giving informed consent. Note: Consent 
must be obtained prior to any study-related procedures. 
14. Subjects must be willing to comply with all study procedures and must be available for the 
duration of the study. 
5.2 Exclusion Criteria 
A subject who meets any of the following criteria at the screening and Day 1 visits, unless specified 
otherwise, will be excluded from participation in this study: 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant 
during the study. 
2. Subject has clinically infected atopic dermatitis. 
3. Subject has a history of skin disease or presence of skin condition that, in the opinion of the 
investigator, would interfere with the study assessments.  
4. Active infection, including skin infection, requiring treatment. 
5. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. 
Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell 
carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded. 
6. Subject has any clinically significant medical condition or physical/laboratory/ECG/vital signs 
abnormality that would, in the opinion of the investigator, put the subject at undue risk or 
interfere with interpretation of study results. 
7. Subject has 12-lead ECG abnormalities considered by the investigator to be clinically 
significant or QTc F ≥ 450 milliseconds, regardless of clinical significance, at screening. 
Abnormal ECG may be confirmed with one repeat assessment. For subjects with QTcF≥450 
msec on initial ECG, the mean of the two QTc F assessments will determine eligibility. 
8. Subject has a history of congestive heart failure New York Heart Association (NYHA) class 
III or IV. 


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9. Subject has a history of erythrodermic, refractory or unstable skin disease, including AD, that 
requires frequent hospitalizations and/or intravenous treatment for skin infections over the last 
year 
10. Subject has a history of eczema herpeticum within 12 months, and/or a history of 2 or more 
episodes of eczema herpeticum in the past. 
11. Subject has a history of recurrent venous thromboembolic event (VTE) (>=2) 
12. Subject has experienced any of the following within the last 6 months prior to Day 1: VTE 
myocardial infarction, angioplasty, or cardiac stent placement, unstable ischemic heart disease, 
or stroke. 
13. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned 
during the study. 
14. Subject is known to have immune deficiency or is immunocompromised. 
15. Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B 
core antigens (anti-HBc), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 
at the screening visit. 
16. Presence of any of the following laboratory abnormalities at the screening visit: 
a. Hemoglobin < 11 g/dL; 
b. White blood cell (WBC) < 3.0 x 103 /μL; 
c. Platelet count < 125 x 103 /μL; 
d. Neutrophils < 1.8 x 103 /μL; 
e. Lymphocytes < 1.0 x 103 /μL; 
f. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 x the upper 
limit of normal (ULN). 
g. Total bilirubin > 1.2 x ULN (except for elevated indirect bilirubin secondary to 
Gilbert’s syndrome); 
h. Creatinine > ULN. 
17. Subjects has uncontrolled hypertension within the last 1 month prior to screening or blood 
pressure at screening of systolic blood pressure >160 mm Hg or diastolic BP >95 mm Hg, 
confirmed by one repeat assessment. 
18. Subject has a known active tuberculosis or a positive tuberculosis (TB) infection test. Subject 
will be evaluated for latent TB infection with a purified protein derivative (PPD) test or a 
QuantiFERON-TB Gold test. Subjects who demonstrate evidence of latent TB infection (either 
PPD ≥5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of bacille 
Calmette-Guérin vaccination status) will only be allowed to participate in the study if there is 
documented evidence of a completed adequate treatment course for latent TB (with negative 
chest x-ray findings for active TB). 
19. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
20. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 


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21. Subject has a known history of diverticulitis. 
22. Subject has uncontrolled diabetes. 
23. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor’s 
medical monitor, would place the subject at risk, interfere with participation in the study, or 
interfere with the interpretation of study results. 
24. Subject has used dupilumab within 12 weeks prior to Day 1.  
25. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser within 
4 weeks prior to Day 1. 
26. Subject has had psoralen-UV-A (PUVA) treatment within 4 weeks prior to Day 1. 
27. Subject has used doxepin within 1 week prior to Day 1. 
28. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
29. Subject has used topical products containing urea within 1 week prior to Day 1. 
30. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior 
to Day 1. 
31. Subject has used any topical medicated treatment for atopic dermatitis within 2 weeks prior to 
Day 1, including, but not limited to, topical corticosteroids, crisaborole and any other topical 
phosphodiesterase-4 inhibitor, calcineurin inhibitors, tars, bleach, antimicrobials, medical 
devices, and bleach baths. 
32. Subject has used systemic treatments (other than biologics) that could affect atopic dermatitis 
less than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, methotrexate, 
cyclosporine, hydroxycarbamide [hydroxyurea], azathioprine, oral/injectable corticosteroids). 
Note: Intranasal corticosteroids, eye drops containing corticosteroids, and inhaled 
corticosteroids for stable medical conditions are allowed.  
33. Subject has received any marketed or investigational biological agent within 12 weeks or 5 
half-lives (whichever is longer) prior to Day 1. 
34. Subject is currently receiving any other medication for AD. 
35. Subject is currently receiving a nonbiological investigational product or device or has received 
one within 4 weeks prior to Day 1. 
36. Subject has excessive sun exposure, is planning a trip to a sunny climate, or has used tanning 
booths within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial 
sunlight exposure during the study. Use of sunscreen products and protective apparel are 
recommended when exposure cannot be avoided. 
37. Subject has received a live attenuated vaccine within 4 weeks prior to Day 1 or plans to receive 
a live attenuated vaccine during the study and up to 4 weeks or 5 half-lives (of the study 
product), whichever is longer, after the last study product administration.  
38. Subject has used ASN002. 


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39. Subject had prior treatment with a systemic SYK or JAK inhibitor for which the subject 
received no clinical benefit in the opinion of the investigator, or the subject relapsed whilst on 
therapy, or was withdrawn for safety reasons. 
40. Subject has a known hypersensitivity to ASN002 or its excipients. 
41. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior 
to Day 1. 
42. Subject has a close affiliation with the investigator (e.g., a close relative) including any study 
staff of the sites or persons working at the CRO or subject is an employee of the sponsor. 
43. Subject is institutionalized because of legal or regulatory order. 
44. Only for subjects consenting to biopsies: 
a. Subject has a history of an allergic reaction or significant sensitivity to lidocaine or 
other local anesthetics; 
b. Subject has a history of hypertrophic scarring or keloid formation in scars or suture 
sites; 
c. Subject is taking anticoagulant medication, such as heparin, low molecular weight 
(LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin which will be 
allowed), within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. 
Nonsteroidal anti-inflammatory drugs [NSAIDs] will not be considered antiplatelets 
and will be allowed. 
5.3 Discontinuation and Lost to Follow-Up 
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 or she feels it is in the best 
interest of the subject or if the subject is uncooperative or noncompliant.  
 
Should a subject decide to withdraw, all efforts will be made to complete and report the 
observations as thoroughly as possible, particularly the examinations outlined in the ET visit. The 
investigator or one of his or her staff members should contact the subject to determine as accurately 
as possible the primary reason for the withdrawal.  
 
A complete final 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 AE or an abnormal laboratory test result, the principal specific event or test will be recorded.  
 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this written request in the site study records. 
 Discontinuation 
Subjects who discontinue the study after the first dose will be asked, if they agree, to come for a 
last assessment (ET visit). Subjects who receive an active treatment for AD after Week 4 visit are 
not necessarily discontinued from the study (refer to section 6.4.2 for more information on how to 
proceed with these subjects). Subjects who have their study product discontinued due to the start 


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of a prohibited medication for the treatment of AD or for any other safety reasons will be asked to 
come back for an additional follow-up visit about 4 weeks after the study product discontinuation 
(in addition to the ET visit). 
 
Subjects who did not complete the study for reasons other than safety, or have demonstrated 
significant noncompliance to study treatments based on IP accountability (define as subject who 
received <80% or >120% of the scheduled doses during the study treatment period) will be 
evaluated by the principal investigator or designee at each visit and may potentially be replaced. 
If a subject drops out during the first 4-week period, the subject may be replaced at sponsor’s 
discretion.  
 
Reasons for discontinuation include the following: 
• 
The investigator decides that the subject should be withdrawn. If this decision is made because 
of a serious adverse event (SAE), the study product is to be discontinued in that subject 
immediately and appropriate measures are to be taken. The investigator will notify the sponsor 
immediately. 
• 
The attending physician requests that the subject be withdrawn from the study. 
• 
The subject, for any reason, requires treatment with another therapeutic agent may be 
discontinued as detailed in section 6.4.2.  
• 
The subject is lost to follow-up. In this case, a reasonable attempt to contact the subject and 
ascertain his or her status must be made, and these attempts must be documented. 
• 
The subject becomes pregnant at any time during the study.  
• 
The subject may withdraw from the study for any other reason, including withdrawal of 
consent. 
• 
The sponsor or regulatory authorities, for any reason, stop the study. In this case, all subjects 
will be discontinued from the study. The investigator will immediately, on discontinuance of 
the study by the sponsor, in its entirety or at a clinical trial site, inform both the subjects and 
the research ethics board of the discontinuance, provide them with the reasons for the 
discontinuance and advise them in writing of any potential risks to the health of subjects or 
other persons. 
 Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she fails to return for scheduled visits and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• 
The site will attempt to contact the subject and reschedule the missed visit. The site will 
then counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain if the subject wishes to or should continue in the study. 
• 
Before a subject is deemed lost to follow-up, the investigator or designee will make every 


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effort to regain contact with the subject (where possible, three telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented in the subject’s medical record or 
study file.  
• 
If all attempts to contact the subject fail, he or she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up. 
5.4 Screen Failures 
Screen failures are defined as individuals who consent to participate in the clinical trial, but are 
not subsequently randomly assigned to the study products. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure subjects, to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements, and to respond 
to queries from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAEs. 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened once, if deemed acceptable by the investigator. Rescreened subjects should be assigned 
a different subject number than the initial screening. All procedures planned at the screening visit, 
including signature of a new consent form, will be performed. 
 
Subjects who do not qualify to participate in the study due to a screening laboratory value 
abnormality can repeat the test once within the original screening time window without resulting 
in screen failure, if the investigator believes there is a reasonable possibility that the subject would 
be eligible if re-tested. 
 
 




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 Duration of Treatment 
The maximum treatment duration per subject is 12 weeks. 
6.2 Preparation/Handling/Storage/Accountability 
 Preparation/Storage/Handling  
All study products must be stored in a secure environmentally controlled and monitored area in 
accordance with the labelled storage conditions with access limited to the investigator and 
authorized site staff.  The study product(s) may only be supplied by authorized site staff and may 
only be given to subjects enrolled into the study.   
 
Study product(s) will be dispensed by the study site to the subject at the visits specified in  
Table 1. Subjects are to return all study product (used and unused) to the study site. The tablets 
will be counted prior to dispensing and upon return, and the counts will be recorded in the source 
documents. Each subject will be instructed on the importance of returning study product at the next 
study visit and on taking the product as prescribed. If a subject does not return study product, he 
or she will be instructed to return it as soon as possible. 
 Accountability  
The investigator is responsible for maintaining accurate records of the study product received 
initially and of the study product dispensed/used. After verification of the study product 
accountability by the sponsor or designee, used product will be stored safely until 
destruction/return. Any study product accidentally or deliberately destroyed, or returned to the 
sponsor or designee will be accounted for. Any discrepancies between amounts dispensed and 
returned will be explained. 
 
All study product accountability forms and treatment logs must be retained in the investigator’s 
study files. Product inventory and accountability records will be maintained as per ICH GCP. 
These records must be available for inspection at any time by the sponsor, its designees, or by 
regulatory agencies. 
 
Further guidance and information for final disposition of study products are provided in the study 
manual.  
6.3 Randomization 
At the investigational site, each screened subject will be assigned a subject identifier number 
during screening that will be used on all subject documentation. The subject identifier number will 
contain the site number and the subject number and will be assigned in numerical order at the 
screening visit based on chronological order of screening dates (e.g., 002-010 for the 10th subject 
screened at the Site #002). 
 


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Approximately 220 subjects will be randomized in a 1:1:1:1 ratio to receive either ASN002 40 mg, 
60 mg, or 80 mg, or placebo, in order to complete the study with 160 evaluable subjects.  
 
Randomization will occur prior to first dosing, at Day 1 visit. The randomization list will be 
generated using a validated software. Randomization will be stratified by baseline disease severity 
at Day 1 ([EASI = 16.0-21.2] vs. [EASI = 21.3-29.9] vs. [EASI = ≥ 30.0]) and biopsy collection. 
The master randomization list will be kept secured until the study blind is broken at the end of 
study. This list will be uploaded into an Interactive Web Response System (IWRS). The 
investigator or designee will be able to acquire a randomization number for eligible subjects by 
connecting to the IWRS. 
 
Further guidance and information can be obtained in the study manual. 
 Blinding 
This study will be double-blinded. At all times, treatment and randomization information will be 
kept confidential and will not be released to the investigator, the study staff, the contract research 
organization (CRO), or the sponsor’s study team until after the conclusion of the study.  
 
Safety oversight will be under the direction of an independent DSMB, who will remain unblinded 
during the study.  
 
Blinding codes should only be broken in emergency situations for reasons of subject safety. If 
unblinding the treatment assignment for a subject is necessary due to a medical emergency (an 
unexpected SAE per product’s safety profile) and other significant medical situations such as 
pregnancy, the investigator can make the decision to unblind the treatment assignment if knowing 
the treatment assignment will help treatment decision of the particular AE. When the blind for a 
subject has been broken, the reason must be fully documented in the source document and eCRF. 
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/time and reason why the 
blind was broken, and the names of the personnel involved. 
 
Emergency unblinding details are provided in the study manual. 
 
The subject for whom the blind has been broken will be discontinued from the study and undergo 
the ET procedures. 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. The primary reason for discontinuation (the event or condition which led to 
the unblinding) will be recorded. 
 Study Product Compliance 
Study product compliance will be monitored at each visit. Adherence to treatment will be assessed 
by direct questioning, review of the subject’s dosing diary, and by maintaining adequate study 


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product dispensing and return records. Any deviation from the prescribed dosage regimen will be 
recorded in the source document and eCRF. 
 
Subjects who are significantly noncompliant with treatment based on IP accountability will be 
counseled and could be discontinued from the study, at the discretion of the investigator, following 
consultation with the sponsor. A subject will also be considered significantly noncompliant if he 
or she intentionally or repeatedly takes more than the prescribed amount of study product in the 
same time frame, as judged by the investigator.  
6.4 Concomitant Therapy 
All medications (including over-the-counter drugs, vitamins, herbal/natural products and antacids) 
taken within 4 weeks prior to screening and throughout the study must be recorded.  
 
Medication entries may be captured as generic or trade names. Trade names should be used for 
combination drugs. Entries should include as much as possible of the following information: the 
dose, unit, frequency of administration, route of administration, start date, discontinuation date, 
and indication. If the medication is discontinued or the dosage is changed, these details must be 
recorded. 
 Permitted Therapies 
Subjects must apply an emollient of their choice (except those containing urea) on their skin. The 
emollient use must be initiated at least 1 week prior to study Day 1 and must be kept at the same 
frequency (once or twice daily) throughout the study until the follow-up visit at Week 16. 
However, on the day of scheduled visits, subjects cannot apply emollient before their scheduled 
visit time.   
 
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. Emollient use will be followed daily in 
the subject diary. 
Use of sunscreen products and protective apparel are permitted when exposure cannot be avoided.  


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 Prohibited Therapies or Procedures 
Table 3 lists prohibited medications that are not to be used from the defined washout periods before 
the first administration of study products at the Day 1 visit through the last study visit.  
 
The discretionary use of concomitant treatments or therapies for atopic dermatitis is prohibited 
between Day 1 and Week 16 visit.  However, should subjects experience an exacerbation of atopic 
dermatitis that requires, in the opinion of the investigator, the use of a prohibited therapy, the 
following approach should be followed:   
 
1. The investigator needs to discuss the case with the medical monitor in order to obtain 
permission to use a prohibited medication. 
2. Subjects who start prohibited medications as a treatment for AD within the first 4 weeks 
of the study will be discontinued from the study product (ASN002 or placebo) and will 
perform the ET visit at the time of discontinuation. In addition, the subject will be asked to 
come back for a follow-up visit 4 weeks after the study product is stopped. Collection of 
PD samples, PK samples, and skin biopsies will not be performed after the ET visit. These 
subjects will not be eligible to participate in the OLE study.  
3. Subjects who start prohibited topical medications as a treatment for AD after the first 
4 weeks of the study may continue all the study assessments up to the last study visit. 
Treatment with the study product may continue concurrently until the end of the treatment 
period, and these subjects will be eligible to participate in the OLE study afterwards. 
Collection of PD samples and skin biopsies will not be performed after the start of a topical 
medication. 
4. Subjects who start prohibited oral corticosteroids as a treatment for AD after the first 
4 weeks of the study will be discontinued from the study product (ASN002 or placebo). 
Use of oral corticosteroids after permanent cessation of ASN002 is permitted only for a 
short period of time (maximum 3 weeks). Subjects should come to all planned study visits 
for safety assessments up to the Week 12 visit.  Collection of PD samples, PK samples, 
and skin biopsies will not be performed after study product discontinuation. These subjects 
will be eligible to participate in the OLE study if they meet the required washout period for 
prohibited medications as defined in the OLE study.   
5. Subjects who start any other prohibited systemic medications as a treatment for AD after 
the first 4 weeks of the study will be discontinued from the study product (ASN002 or 
placebo) and will perform the ET visit at the time of discontinuation. In addition, the 
subject will be asked to come back for a follow-up visit 4 weeks after the study product is 
stopped. Collection of PD samples, PK samples, and skin biopsies will not be performed 
after the ET visit. These subjects may be eligible to participate in the OLE study not earlier 
than 12 weeks after Day 1 of the present study and only if they meet the required washout 
period for prohibited systemic medications as defined in the OLE study.   
6. Subjects who start any other prohibited medications or therapies for other reasons may be 
withdrawn from the study, at the investigator’s discretion in agreement with the medical 
monitor and the sponsor. 
 
If in any doubt, investigators are advised to discuss medications with the medical monitor. 






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7 
STUDY ASSESSMENTS AND PROCEDURES 
7.1 Efficacy Assessments 
Clinical evaluations of atopic dermatitis will be performed by an experienced and qualified 
dermatologist (board certified or equivalent) or other suitably qualified and experienced designee. 
To assure consistency and reduce variability, the same assessor should perform all assessments on 
a given subject whenever possible. 
 Eczema Area and Severity Index 
The Eczema Area and Severity Index (EASI) will be assessed at the visits specified in Table 1 
before the study product administration. It quantifies the severity of a subject’s atopic dermatitis 
based on both lesion severity and the percentage of BSA affected (18). The EASI is a composite 
score ranging from 0 to 72 that takes into account the degree of erythema, induration/infiltration 
(papules), excoriation, and lichenification (each scored from 0 to 3 separately) for each of four 
body regions, with adjustment for the percentage 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 B. To be eligible for this study, subjects must have an EASI 
score of ≥16 at Day 1. 
 Investigator Global Assessment 
The Investigator Global Assessment (IGA) of disease severity will be assessed at the visits 
specified in Table 1 before the study product administration. The IGA is a global assessment of 
the current state of the disease. It is a 5-point morphological assessment of overall disease severity. 
A detailed description of the IGA scale is provided in Appendix C. To be eligible for this study, 
subjects must have an IGA score of ≥3 at Day 1. 
 SCORing Atopic Dermatitis  
The SCORing Atopic Dermatitis (SCORAD) will be measured at the visits specified in Table 1 
before the study product administration. The SCORAD grading system was developed by the 
European Task Force on Atopic Dermatitis (1993) and has been a standard tool to assess AD 
severity in clinical studies in Europe (19, 20). Six items (erythema, edema/papulation, 
oozing/crusts, excoriation, lichenification, and dryness) will be evaluated 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 subjects on a visual analog scale (0-10) and 
should be based on the average of the last three days/nights. The sum of these measures represents 
the SCORAD, which can range from 0 to 103. The detailed procedure of SCORAD score 
calculation is provided in Appendix D.  
 Body Surface Area 
The overall Body Surface Area (BSA) affected by AD will be evaluated (from 0% to 100%) at the 
visits specified in Table 1 before the study product administration. One subject’s palm represents 




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  Dermatology Life Quality Index Questionnaire  
The Dermatology Life Quality Index (DLQI) will be assessed at the visits specified in Table 1. It 
is a simple 10-question validated questionnaire that has been used in more than 40 different skin 
conditions. Its use has been described in more than 1,000 publications, including many 
multinational studies. The DLQI is the most frequently used instrument in studies of randomized 
controlled trials in dermatology. The questionnaire is provided in Appendix G. 
7.3 Safety Assessments  
 Vital Signs 
The following vital signs will be recorded at the visits specified in Table 1 with the subject in a 
seated position, after having sat calmly for at least 5 minutes: systolic and diastolic blood pressure 
(mmHg), pulse (bpm), and body temperature (°C). 
 
Weight (kg) and height (cm) will be collected to calculate the BMI and will be recorded at the 
visits specified in Table 1. The height will only be recorded at the screening visit and the same 
value will be used for BMI calculation at other visits. 
 
If deemed appropriate by the investigator, clinically significant findings in the vital signs will 
exclude a subject from study participation. Any abnormal finding related to vital signs that the 
investigator considers to be clinically significant must be recorded as an AE. 
 Physical Examination 
The following sites/systems will at least be included in the physical examination, which will be 
performed at the visits specified in Table 1:  
 
• General appearance 
• Dermatological (except atopic dermatitis) 
• Head, eyes, ears, nose, throat (HEENT) 
• Respiratory 
• Cardiovascular 
• Abdominal 
• Neurological 
• Musculoskeletal 
• Lymphatic  
Information for all physical examinations must be included in the source document. If deemed 
appropriate by the investigator, clinically significant findings in the physical examination will 
exclude a subject from study participation. Any significant change will be reported as an AE in 
the source document and eCRF. 


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 Brief Physical Examination  
The following sites/systems will at least be included in the brief physical examination that will be 
performed at the visits specified in Table 1:  
 
• General appearance 
• Dermatological (except atopic dermatitis) 
• Respiratory 
• Cardiovascular 
• Abdominal 
 
Information for all physical examinations must be included in the source document. If deemed 
appropriate by the investigator, clinically significant findings in the physical examination will 
exclude a subject from study participation. Any significant change will be reported as an AE in 
the source document and eCRF.  
 Clinical Laboratory Tests 
Laboratory tests will be performed at the visits specified in Table 1. The tests will include 
urinalysis, hematology with differential, a standard chemistry panel (chemistry includes liver 
function tests and cholesterol), and serum pregnancy test (screening) for women of childbearing 
potential (WOCBP). At the visit specified in Table 1, a urine pregnancy test will be performed for 
WOCBP (conducted at the investigator site). The specific tests in these panels are listed in  
Table 5. 
 




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7.4 
Pharmacokinetic and Pharmacodynamic Assessments 
 Pharmacokinetics Assessments  
Blood samples will be collected for PK assessment on visits and time points indicated in the 
schedule of events in Table 1. Measurement of plasma concentrations of ASN002 will be 
performed in all subjects receiving ASN002 treatment. A few samples from each of the placebo 
subjects (e.g., pre-dose on Day 1 and 2 hours at Week 4) may be analyzed for quality control 
purposes. 
 
The actual date and time of each blood sample collection will be recorded. Approximately 4 mL 
of blood will be collected for each time point.  
 
Details about the collection, processing, handling, storage and shipping of blood samples will be 
provided in the laboratory manual. 
 
Non-compartmental PK analysis will not be performed for this study. 
 
Population PK analysis will be performed using nonlinear mixed-effects modeling approach with 
first-order conditional methods. This analysis may be combined with PK concentrations from other 
clinical trials in healthy and AD subjects as appropriate. The results from this analysis may be 
reported separately. 
 Pharmacodynamics Assessments  
At selected study centers, for a subset of approximately 68 subjects who consent to the procedure, 
blood samples will be collected for PD analysis on visits indicated in the schedule of events in 
Table 1. PD samples will be drawn as trough samples prior to the study product administration. 
PD samples will be obtained from the same subjects who consent to biopsy collection.  
 
The actual date and time of each blood sample collection will be recorded. Approximately 8 mL 
of blood will be collected for each time point.  
 
Details about the collection, processing, handling, storage and shipping of blood samples will be 
provided in the laboratory manual. 
 PK/PD Relationship Assessments  
PK-efficacy, PK-safety and PK-biomarkers relationships will be explored using linear regression, 
loess plots, Hills functions, or logistic regression, as appropriate. The results from these analyses 
may be reported separately. 


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 Skin Biopsies 
At selected study centers, for a subset of approximately 68 subjects who consent to the procedure, 
three or four optional skin biopsies will be collected at the visits specified in Table 1. Two 4.5-mm 
punch biopsies (one from lesional skin and one from adjacent nonlesional skin) will be collected 
at Day 1, and one 4.5-mm punch biopsy will be collected from the same lesional skin (outside the 
scar of the previous biopsy, at least 1 cm away from the previous scar) at Week 12 or ET visit (if 
applicable). In addition, one 4.5-mm punch biopsy will be collected from the same lesional skin 
(outside the scar of the previous biopsy, at least 1 cm away from the previous scar) at Week 4 in 
subjects who consent to four skin biopsies. Biopsy samples will be obtained from the same subjects 
who consent to PD samples. 
 
The skin will be cleaned, disinfected, and anesthetized before skin biopsies are performed. Sterile 
gauze will be used to absorb any bleeding. The biopsy sites will be sutured if necessary. 
 
Each biopsy will be split in half. One part will be used for a limited immunohistochemistry panel 
and the other part will be used for gene expression analysis. 
 
Details about the collection, processing, handling, storage and shipping of biopsy samples will be 
provided in the laboratory manual. 
7.5 
Other Assessments 
 Medical Photography 
At selected study centers, for a subset of approximately 68 subjects who consent to the procedure, 
medical photographs will be performed at the visits specified in Table 1. Photographs of the area 
of worst eczema involvement will be taken to illustrate any visible clinical change. A target area 
for each participant will be identified at Day 1, and the same area will be photographed at the other 
visits.  Care will be taken to use the same camera, the same magnification, and the same settings 
for each photograph at each visit in order to obtain comparable pictures. Medical photographs will 
be taken using a blue background.  
 
Photographs will be identified and stored as instructed in the photography manual. 


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7.6 Adverse Events and Serious Adverse Events 
 Definition of Adverse Event 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
and that does not necessarily have a causal relationship with this treatment. An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a study product, whether or not considered related to 
the study product. AEs and SAEs will be collected from the time of informed consent signature 
until the final visit / contact. 
 Definition of Treatment-Emergent Adverse Event 
A TEAE is any condition that was not present prior to treatment with the study product but 
appeared following treatment, was present at treatment initiation but worsened during treatment, 
or was present at treatment initiation but resolved and then reappeared while the individual was on 
treatment (regardless of the intensity of the AE when the treatment was initiated). 
 Definition of Serious Adverse Event 
A serious adverse event or reaction is any untoward medical occurrence that, at any dose has any 
of the following consequences: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires in-patient hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
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 that 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. 


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 Classification of an Adverse Event 
7.6.4.1 Relationship to Study Product 
 
The investigator will establish causality of the AE to the experimental treatment. The investigator 
should take into account the subject’s history, most recent physical examination findings, and 
concomitant medications.  
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale:  
Not related indicates that there is not a reasonable possibility for relationship of the event to 
the study medication.  
Possibly related indicates that a direct cause and effect relationship between study medication 
and the AE has not been demonstrated, but there is evidence to suggest there is a reasonable 
possibility that the event was caused by the study medication. 
Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
 
The statement "reasonable possibility for relationship" meaning that there are facts (e.g., 
evidence such as de-challenge/re-challenge/temporal relationship, exposure, likely cause due to 
known safety profile etc) to suggest a positive causal relationship. The investigators may also 
change their opinion for causality after follow-up information and may provide a follow-up SAE 
report with the revised causality assessment. 
 
7.6.4.2 Adverse Event 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: 
• 
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. 
7.6.4.3 Expectedness 
 
The expectedness of each SAE in relation to the study product will be determined, in consultation 
with the Sponsor when necessary. 


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 Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study subject presenting for medical care, or upon review by a study monitor. 
 
All AEs, including local and systemic reactions, will be captured on the appropriate eCRF. 
Information to be collected includes event description, date of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to 
make a diagnosis), and date of resolution/stabilization of the event. All AEs occurring while on 
study must be documented appropriately regardless of relationship.  
 
Before subject 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 eCRF. During 
the study, site personnel will note any change in the condition(s) and the occurrence and nature of 
any AE.  
 
Any medical condition that is present at the time of consent signature will be considered as part of 
medical history and not reported as an AE. However, if the study subject’s condition deteriorates 
after the consent signature, it will be recorded as an AE. 
 
If a subject experiences an AE at any time after the informed consent signature until the end of 
participation in the study, the event will be recorded as an AE in the source document and eCRF. 
Any SAE related to the study participation (e.g., screening procedure) will be recorded in the 
source document and eCRF from the time a subject consents to participate in the study until the 
end of participation in the study. 
 
The investigator is responsible for appropriate medical care of subjects during the study. The 
investigator also remains responsible for following through with an appropriate health care option 
for all AEs that are ongoing at the end of the study. The subject should be followed until the event 
is resolved or stable. If an AE is ongoing at the end of study, the follow-up duration is left to the 
discretion of the investigator. Follow-up frequency will be performed at the discretion of the 
investigator.  
 
Whenever possible, clinically significant abnormal laboratory results are to be reported using the 
diagnostic that resulted in the clinically significant abnormal laboratory results and not the actual 
abnormal test. 
 
Worsening of atopic dermatitis is captured by efficacy assessments and will not be recorded as an 
AE.   
 Adverse Event Reporting 
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.  




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 Pregnancy Reporting 
If a female subject or a female partner of a male subject becomes pregnant during the study, the 
subject should inform the study site as soon as possible. Upon confirmation of the pregnancy, the 
female subject will be discontinued from the study. The investigator must complete a 
study-specific pregnancy form upon confirmation of a pregnancy and send it to 
 within 
24 hours of confirmation of the pregnancy (contact information to be used is the same as for SAE 
reporting). 
will report all cases of pregnancy to the sponsor and CRO in a timely manner. 
Posttreatment 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, in the case of a live-born offspring, to 1 month of age in that infant. The 
investigator will notify 
and CRO of the outcome as a follow-up to the initial pregnancy form. 
All pregnancies should be reported to the sponsor and, when applicable, to the ethics committee. 
 
In the case of an SAE or pregnancy, the subject treatment assignment may be unblinded if judged 
necessary by the investigator and/or medical monitor in consultation with the sponsor. Once the 
subject treatment assignment is unblinded, the subject for whom the blind has been broken will be 
discontinued from the study and undergo the ET procedures. 
 Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated per protocol for a given subject. Study drug compliance (see section 6.3.2) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
 
Any study drug overdose during the study should be recorded on the source document and eCRF. 
In the event of overdose, the subject should be closely monitored for any potential AEs. All AEs 
associated with an overdose should be entered on the Adverse Event eCRF and reported using the 
procedures detailed in section 7.6.7, Serious Adverse Events Reporting, even if the events do not 
meet seriousness criteria. If the AE associated with an overdose does not meet seriousness criteria, 
it must still be reported using the SAEs reporting procedures and in an expedited manner, but 
should be noted as non-serious on the form and the Adverse Event eCRF. The excess quantity and 
duration of the overdose should be recorded. 


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8 
STATISTICAL CONSIDERATIONS  
8.1 Sample Size Determination 
Using the following assumptions for the primary efficacy endpoint: a change-from-baseline in 
EASI at week 12 of at least -15 in the ASN002 dosing groups, a change-from-baseline of -8 in the 
placebo group, a common standard-deviation of 8, nominal alpha of 0.0167 for each comparison 
of interest, we would need 40 evaluable subjects per group in order to achieve a power of 92% on 
the primary efficacy endpoint. 
 
Moreover, with 46 subjects per group, we would have 80% power to show a statistically 
significant difference between the higher dosing group and placebo in IGA responses (one of the 
key secondary efficacy endpoint), assuming a response of 37.5% vs. 11.1% in the higher dosing 
and placebo groups, respectively, using an alpha of 5%.   
 
Thus, assuming about 15% dropout rate, 55 subjects per group will need to be enrolled in this 
trial for a total of 220 subjects in order to have a minimum of 46 subjects per group to evaluate 
efficacy with adequate power. 
8.2 Populations for Analyses 
Modified Intent-to-Treat Population (mITT): This population will include all subjects who 
received at least one dose of the study product. All subjects will be analyzed according to the 
treatment group to which they were randomized. The mITT population will be used as the primary 
analysis population for efficacy. 
 
The Per Protocol Population (PP): This population will include all subjects who were randomized, 
who received at least one dose of study product, with no significant protocol deviations, and who 
provided evaluable data for the primary endpoint. All subjects will be analyzed according to the 
treatment group that they actually received. 
 
The Safety Population (SAF): This population will include all subjects who received at least one 
dose of the study product. All subjects will be analyzed according to the treatment group that they 
actually received. 
 
The PK Population: This population will include all subjects who received at least one dose of 
ASN002 and have plasma concentration data. 
 
The PD Population: This population will include all subjects who have at least one assessments of 
PD parameters 


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8.3 Statistical Analyses 
 General Approach 
Continuous variables will be summarized in tables and will include the number of subjects, mean, 
standard deviation, median, minimum, and maximum. Categorical variables will be presented in 
tables as frequencies and percentages.  
 
The primary efficacy analysis will be done using the mITT population and the PP population will 
be used as supportive analysis. All efficacy analyses will be performed using Mixed Model 
Repeated Measures (MMRM) analyses as primary analyses to take care of missing observations. 
Moreover, the analyses performed on observed case (i.e. without imputation of missing 
observations) will be done as sensitivity analyses. 
 
Additional details regarding the efficacy and safety variable definitions, analyses strategy, control 
of the overall type 1 error, statistical justification, and techniques for handling missing values (e.g. 
for subjects who started prohibited medications) will be detailed in a SAP that will be prepared 
before the database is locked and any analyses are undertaken.  
 Efficacy Analyses 
The primary efficacy endpoint will be analyzed using a repeated measures analysis of covariance 
on change-from-baseline variable to compare the time profile between treatments where the visit 
will be the time factor; and the stratification factors, treatment group, and interaction term for 
treatment-by-visit will be the fixed effects and the baseline value will be the covariate. An 
unstructured variance-covariance matrix will be used. Additional interaction terms will also be 
included in supportive statistical models and will be detailed in the SAP. 
 
Sensitivity Analyses: 
 
An analysis of covariance (ANCOVA) will be performed, where the absolute change from baseline 
at Week 12 will be the dependent variable; the treatment group and the stratification factors will 
be the fixed effects; and the baseline value will be the covariate. A supportive analysis with Site 
and Site-by-Treatment interaction included as fixed factors in addition to the other factors listed 
above will be performed in order to study the impact of site on efficacy. 
 
A similar approach as for the primary endpoint will be done for all other continuous efficacy 
endpoints.  
 
For categorical efficacy endpoints involving proportions of IGA, EASI and NRS (e.g. the 
proportion of subjects achieving at least a 2-grade reduction from baseline to clear (0) or almost 
clear (1) in Investigator’s Global Assessment (IGA) at week 12), a Cochran Mantel Hansel test 
(CMH) controlling for the stratification variables will be performed. 
 


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Overall type 1 error control 
For the primary endpoint of change-from-baseline in EASI at Week 12, a Bonferroni adjustment 
will be done to test the three comparisons of interest (40mg vs. Placebo, 60mg vs. Placebo and 
80mg vs. Placebo) at alpha of 0.0167.  
 Safety Analyses 
All safety data, including AEs and SAEs will be presented and tabulated according to Medical 
Dictionary for Regulatory Activities (MedDRA) classification. Descriptions of AEs will include 
the start date, the stop date (if it resolved), the severity and seriousness of the AE, the causality of 
the AE to study product, and the outcome. The focus in this protocol will be the prevalence of 
TEAEs and drug-related TEAEs. 
 
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 product. For 
the summary of AEs by severity, each subject 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 product, each subject 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 product and severity, each subject 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 subject, detailing 
verbatim, System Organ Class, Preferred Term, start date, stop date, intensity, outcome, and 
relationship to study product. The AE onset will also be shown relative (in number of days) to the 
day of study product administration. 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. 
 
Results from laboratory analyses, vital signs, ECGs, and physical examinations will be tabulated 
by treatment and visit using descriptive statistics. The value at each visit as well as the change 
from baseline will be presented descriptively.  
 
Concomitant medications will be coded with the World Health Organization (WHO) Drug 
Dictionary and listed by subject. Summary of medication classes will also be tabulated.  
 
No inferential statistics will be done on safety variables. 
 Pharmacokinetic Analyses 
ASN002 concentration data will be listed per subject and summarized descriptively per dose.  
 


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Individual plasma concentration vs. actual time profiles for each subject and treatment, as well as 
the mean (±SD) plasma concentration vs. scheduled time profiles for each dose level, will be 
presented graphically.  
 Pharmacodynamic Analyses 
A biomarker analysis will be performed on blood and biopsy samples collected to evaluate PD 
effects of ASN002 on inflammatory markers and cell populations. Biomarker levels will be 
compared to placebo adjusted change from baseline over time for each treatment group, and the 
parameters will be summarized by treatment group and overall using descriptive statistics.  
 Other Analyses 
Descriptive summaries of baseline characteristics, including demographic data, prior concomitant 
therapy, and of subject disposition will be presented. In addition, a list of subjects who 
discontinued from the study will be provided 
 
Protocol deviations will be summarized by treatment and category. 
 Planned Interim Analysis 
No formal interim analyses are planned for this study.  However, unblinded safety data will be 
generated and reviewed by the DSMB during the study.  
 


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9 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
9.1 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 and that are consistent with ICH Tripartite Guideline for GCP and the 
applicable laws and regulations of the country in which the research is conducted, whichever 
affords the greater protection to the individual.   
9.2 Ethical Review  
It is the understanding of the sponsor that this protocol (and any amendments) as well as 
appropriate consent procedures, will be reviewed and approved by an IRB/EC. This board must 
operate in accordance with the current federal regulations. For sites with a local ethics committee, 
a letter or certification of approval will be sent by the investigator to the sponsor (or CRO) before 
initiation of the study and also whenever subsequent modifications to the protocol are made.   
9.3 Informed Consent Process 
An Informed Consent Form describing in detail the study products, study procedures, and risks 
will be given to the subject, along with an assent form when required.  
 
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.   
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be IRB/EC 
approved, and the subject will be asked to read and review the document. The investigator will 
explain the research study to the subject and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the subject’s comprehension of the purposes, 
procedures, and potential risks of the study and of his or her rights as a research subject.  Subjects 
will have the opportunity to carefully review the written consent form and ask questions prior to 
signing. The subjects should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate.  
 
The subject will sign the informed consent document prior to any procedures being done 
specifically for the study. Subjects must be informed that participation is voluntary and that they 
may withdraw from the study at any time for any reason, without prejudice. A copy of the signed 
informed consent document will be given to the subjects for their records. The informed consent 
process will be conducted and documented in the source document (including the date), and the 
form signed, before the subject undergoes any study-specific procedures.  
 
The rights and welfare of the subjects will be protected by emphasizing to them that the quality of 


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their medical care will not be adversely affected if they decline to participate in this study. 
 
If new safety information results in significant changes in the risk/benefit assessment, or if any 
new information becomes available that may affect the willingness of a subject to continue to 
participate, the consent form should, if necessary, be reviewed and updated by the IRB/EC. 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. 
9.4 Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study subjects, 
investigators, the sponsor, and regulatory authorities.  If the study is prematurely terminated or 
suspended, the principal investigators will promptly inform study subjects and the IRB/EC, and 
will provide the reason(s) for the termination or suspension.  Study subjects will be contacted, as 
applicable, and be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension of the study include, but are not limited 
to the following: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete or evaluable 
• 
Scientific or corporate reasons 
 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the sponsor, IRB/EC, and applicable local regulations. 
9.5 Confidentiality and Privacy  
Subject confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor and their interventions. This confidentiality is extended to cover testing of 
biological samples in addition to the clinical information relating to subjects. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence.  
 
The investigator must assure that the subjects’ anonymity will be maintained and that subjects’ 
identities are protected from unauthorized parties. On case report forms or other documents 
submitted to the sponsor, subjects should not be identified by their names, but by an identification 
code. The investigator should keep a subject enrollment log relating codes with the names of 
subjects. The investigator should maintain in strict confidence documents not for submission to 
the sponsor (e.g., subjects’ written consent forms). 
 
All research activities will be conducted in a setting as private as possible. 
 
The study monitor, other authorized representatives of the sponsor, and representatives of the 


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IRB/EC, regulatory agencies, or pharmaceutical company supplying study product may inspect all 
documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. 
The clinical study site will permit access to such records. 
 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the applicable legal or regulatory requirements, the reviewing 
IRB/EC, institutional policies, or sponsor requirements. 
9.6 Clinical Monitoring 
Clinical site monitoring will be conducted to ensure that the rights and well-being of trial subjects 
are protected; that the reported trial data are accurate, complete, and verifiable; and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), ICH GCP 
guidelines, and with applicable regulatory requirement(s). Details of clinical site monitoring will 
be documented in a Monitoring Plan. 
9.7 Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation, and completion.   
 
Quality control (QC) procedures will be implemented beginning with the data entry system, and 
data QC checks, which will be run on the database, will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
 
During the study, the sponsor or its representative will conduct monitoring visits at regular 
intervals. The monitoring visits will be conducted to ensure protocol adherence, quality of data, 
accuracy of entries on the eCRFs, study product accountability, compliance with regulatory 
requirements, and continued adequacy of the investigational site and its facilities.  
 
The site may be audited, monitored, or inspected by a quality assurance officer named by the 
sponsor, by the IRB/EC, and/or by the regulatory authorities. The investigator will be given notice 
before an audit occurs and will be expected to cooperate with any audit and provide assistance and 
documentation (including source data) as requested. The investigational site will provide direct 
access to all trial-related sites, source data/documents, and reports for the purpose of monitoring 
and auditing by the sponsor and inspection by local and regulatory authorities. 
9.8 Data Handling and Record Keeping 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
 
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 documents should be 




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10 
REFERENCES 
1. 
Williams HC. Atopic eczema. Bmj. 1995;311(7015):1241-2. 
2. 
Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. 
Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment 
of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116-32. 
3. 
Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting 
paradigms in treatment approaches. J Allergy Clin Immunol. 2014;134(4):769-79. 
4. 
Silverberg JI. Persistence of childhood eczema into adulthood. JAMA Dermatol. 
2014;150(6):591-2. 
5. 
Cabanillas B, Brehler AC, Novak N. Atopic dermatitis phenotypes and the need for 
personalized medicine. Curr Opin Allergy Clin Immunol. 2017;17(4):309-15. 
6. 
Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with 
childhood eczema. International journal of clinical practice. 2006;60(8):984-92. 
7. 
Marciniak J, Reich A, Szepietowski JC. Quality of Life of Parents of Children with Atopic 
Dermatitis. Acta Derm Venereol. 2017;97(6):711-4. 
8. 
Mochizuki H, Schut C, Nattkemper LA, Yosipovitch G. Brain mechanism of itch in atopic 
dermatitis and its possible alteration through non-invasive treatments. Allergol Int. 2017;66(1):14-
21. 
9. 
Bieber T, D'Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G, et al. 
Clinical phenotypes and endophenotypes of atopic dermatitis: Where are we, and where should we 
go? J Allergy Clin Immunol. 2017;139(4S):S58-S64. 
10. 
Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its 
reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 
2017;139(4S):S65-S76. 
11. 
Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. 
Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment 
of atopic dermatitis. J Am Acad Dermatol. 2014;70(2):338-51. 
12. 
Brunner PM, Silverberg JI, Guttman-Yassky E, Paller AS, Kabashima K, Amagai M, et al. 
Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder. J Invest 
Dermatol. 2017;137(1):18-25. 
13. 
Guttman-Yassky E, Ungar B, Malik K, Dickstein D, Suprun M, Estrada YD, et al. 
Molecular signatures order the potency of topically applied anti-inflammatory drugs in patients 
with atopic dermatitis. J Allergy Clin Immunol. 2017;140(4):1032-42 e13. 
14. 
Riccaboni M, Bianchi I, Petrillo P. Spleen tyrosine kinases: biology, therapeutic targets 
and drugs. Drug Discov Today. 2010;15(13-14):517-30. 
15. 
Pesu M, Laurence A, Kishore N, Zwillich SH, Chan G, O'Shea JJ. Therapeutic targeting of 
Janus kinases. Immunol Rev. 2008;223:132-42. 
16. 
Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E, et al. Cellular 
and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin 
Immunol. 2016;138(2):336-49. 
17. 
Kyttaris VC, Tsokos GC. Syk kinase as a treatment target for therapy in autoimmune 
diseases. Clin Immunol. 2007;124(3):235-7. 


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18. 
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. 
19. 
Rullo VE, Segato A, Kirsh A, Sole D. Severity scoring of atopic dermatitis: a comparison 
of two scoring systems. Allergol Immunopathol (Madr). 2008;36(4):205-11. 
20. 
Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the 
European Task Force on Atopic Dermatitis. Dermatology. 1993;186(1):23-31. 
21. 
Phan NQ, Blome C, Fritz F, Gerss J, Reich A, Ebata T, et al. Assessment of pruritus 
intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating 
scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 
2012;92(5):502-7. 
22. 
Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. 
Br J Dermatol. 2010;162(3):587-93. 
23. 
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. Archives of dermatology. 2004;140(12):1513-9. 
24. 
The patient-oriented eczema measure: development and initial validation of a new tool for 
measuring atopic eczema severity from the patients' perspective - correction. Archives of 
Dermatology. 2005;141(3):381. 
25. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermato-
Venereologica Supplementum. 1980;92:44-7. 
 
 


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APPENDIX A: 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.(25) The criteria are 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 chronically relapsing dermatitis 
• Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis) 
 
Minor Criteria (must have at least three) 
• Xerosis 
• Ichthyosis/keratosis pilaris/palmar 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  
• Tendency to nonspecific hand/foot dermatitis 
• Nipple eczema 
• Cheilitis 
• Recurrent conjunctivitis 
• Dennie-Morgan infraorbital 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 dermographism/delayed blanch 
 


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APPENDIX B: Eczema Area and Severity Index  
 
Four anatomic sites—head, upper extremities, trunk, and lower extremities—are assessed for 
erythema, induration/infiltration (papules), excoriation, and lichenification as seen on the day of 
the examination. The severity of each sign is assessed using a 4-point scale (half steps are 
allowed): 
 
• 
0 = none 
• 
1 = mild 
• 
2 = moderate 
• 
3 = severe 
 
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 below: 
 
EASI = 0.1 (Eh + Ih + Exh + Lh) Ah + 0.2 (Eu + Iu + Exu + Lu) Au + 0.3 (Et + It 
+ Ext + Lt) At + 0.4 (El + Il + Exl + Ll) 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. 
 


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APPENDIX C: vIGA-ADTM 
 


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APPENDIX D: Scoring Atopic Dermatitis - SCORAD 
 
Six items (erythema, edema/papulation, oozing/crusts, excoriation, lichenification, and dryness) 
are selected to evaluate the atopic dermatitis severity. The intensity of each item is graded using a 
4-point scale (half steps not allowed): 
 
• 
0 = absence 
• 
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 atopic dermatitis is evaluated (from 0% to 100%) and divided by 5. 
One subject’s palm represents 1% of his or her total BSA. The maximum is 20. 
 
Subjective items include loss of sleep and the occurrence of pruritus. These are 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 3 days/nights. The combined maximum score of these two is 20. 
 
The sum of the measures above 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). 
 
 


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APPENDIX E: Patient-Oriented Eczema Measure  
 


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APPENDIX F: Patient-Oriented Eczema Measure  
 
Subject ID #: ___ ___ - ___ ___ ___  
 
Subject 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. 
 


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APPENDIX G: Dermatology Life Quality Index  
 
Subject ID #: ___ ___ - ___ ___ ___  
 
Subject 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  
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  
 
 
 
 
 
 


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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. 
 

SAP_003.pdf: 


STATISTICAL ANALYSIS PLAN, Version  
Final 2.0 
 
Protocol Number: ASN002AD-201 
V3.0 
Sponsor: Asana BioSciences, LLC 
 
 Proprietary & Confidential 
Page 2 of 41 
 
STATISTICAL ANALYSIS PLAN REVISION SUMMARY 
Version 
Version Date 
Author 
Summary of Changes  
Original V1.0 
26-NOV-2018 
  
Initial version 
Original V2.0 
12-FEB-2019 
  
Updated text based on sponsor’s comments. 
Final V1.0 
01-Aug-2019 
  
Updated text based on sponsor’s comments. 
Final V2.0 
12-Aug-2019 
  
Added text excluding site 027 from all 
analyses. 
Updated the denominator used for 
discontinued subjects. 
 
 
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STATISTICAL ANALYSIS PLAN, Version  
Final 2.0 
 
Protocol Number: ASN002AD-201 
V3.0 
Sponsor: Asana BioSciences, LLC 
 
Proprietary & Confidential 
Page 38 of 41 
15 REFERENCES