Clinical trial NCT03654755
Conditions: Atopic Dermatitis
Keywords: eczema
Sponsor: Asana BioSciences
Start date: 2018-09-29; Completion date: 2019-10-29
Enrollment: 162 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a randomized open label study to evaluate the long term safety of ASN002 in subjects with moderate to severe atopic dermatitis (AD).

Detailed description:
This is a randomized open label study where subjects with moderate to severe atopic dermatitis will roll over from the Phase 1 ASN002AD-101 (NCT03139981) and ASN002AD-201 (NCT03531957) Ph2b study and be randomized to receive ASN002 at 40mg, 60mg, or 80mg once daily for up to 24 months. This study will also characterize the pharmacokinetics of ASN002 through blood sampling from subjects who consent.

Arms: arm 1: ASN002 40 mg arm 2: ASN002 60 mg arm 3: ASN002 80 mg
Interventions: intervention 1: ASN002
Intervention descriptions: intervention 1: Daily dose of ASN002 for up to 110 weeks

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
Page 1 of 79  
 
 
 
 
 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 
 
A PHASE 2, MULTICENTER, OPEN-LABEL EXTENSION STUDY TO 
EVALUATE THE LONG-TERM SAFETY, TOLERABILITY AND 
EFFICACY OF ASN002 IN SUBJECTS WITH MODERATE TO SEVERE 
ATOPIC DERMATITIS 
 
PROTOCOL ASN002AD-201-EXT 
IND # 133693 
 
FINAL, VERSION 2.0 
07 February 2019 
 
Sponsor: 
Asana BioSciences, LLC. 
 
 
 
Sponsor Contacts :  
 
Telephone (office): 
 
E-mail: 
 
 
– Portfolio Management 
Telephone (office): 
  
E-mail: 
 
 
 Chief Medical Officer 
Telephone (office): 
 
E-mail: 
 
Primary Medical 
Monitor: 
 
 
Telephone: 
 
Local Medical Monitors: United States/Canada: 
  
 
 
 
 
 
  
Telephone: 
 
Telephone (24h/7d): 
 
Fax: 
 
Germany: 
 
 
 
 
  
Telephone: 
 
Telephone (24h/7d): 
 
Fax: 
 
Clinical Research 
Organization: 
 
 
 
 
 
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Asana BioSciences, LLC– Protocol ASN002AD-201-EXT 
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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 .............................................................................................................. 25 
1.3 
Schedule of Events ........................................................................................................ 25 
2 
INTRODUCTION ........................................................................................................ 28 
2.1 
Background ................................................................................................................... 28 
 
Atopic Dermatitis .................................................................................................. 28 
 
ASN002 in Atopic Dermatitis ................................................................................ 28 
 
Study Rationale ..................................................................................................... 29 
2.2 
Risk/Benefit Assessment ............................................................................................... 30 
 
Known Potential Risks .......................................................................................... 30 
 
Known Potential Benefits ...................................................................................... 30 
 
Assessment of Risks and Benefits .......................................................................... 30 
3 
OBJECTIVES AND ENDPOINTS .............................................................................. 31 
4 
STUDY DESIGN .......................................................................................................... 33 
4.1 
Overall Design .............................................................................................................. 33 
4.2 
Scientific Rationale for Study Design ........................................................................... 34 
4.3 
End of Study Definition ................................................................................................ 34 
4.4 
Safety 
Monitoring 
Criteria 
for 
Individual 
Subject 
Treatment 
Interruption/Discontinuation ......................................................................................... 34 
 
Interruption criteria .............................................................................................. 35 
 
Permanent study discontinuation .......................................................................... 35 
4.5 
Safety Monitoring ......................................................................................................... 35 
5 
STUDY POPULATION ............................................................................................... 37 
5.1 
Inclusion Criteria ........................................................................................................... 37 
5.2 
Exclusion Criteria ......................................................................................................... 40 


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5.3 
Discontinuation and Lost to Follow-Up ........................................................................ 44 
 
Discontinuation ..................................................................................................... 45 
 
Lost to Follow-Up ................................................................................................. 45 
5.4 
Screen Failures .............................................................................................................. 46 
6 
TREATMENT .............................................................................................................. 47 
6.1 
Study Products Administered ........................................................................................ 47 
 
Missed or Vomited Doses...................................................................................... 47 
 
Duration of Treatment .......................................................................................... 47 
6.2 
Preparation/Handling/Storage/Accountability .............................................................. 48 
 
Preparation/Storage/Handling ............................................................................. 48 
 
Accountability ....................................................................................................... 48 
6.3 
Randomization .............................................................................................................. 48 
 
Blinding ................................................................................................................. 49 
 
Study Product Compliance ................................................................................... 49 
6.4 
Concomitant Therapy .................................................................................................... 50 
 
Permitted Therapies .............................................................................................. 50 
 
Prohibited Therapies or Procedures .................................................................... 51 
 
Concomitant Use of Drugs that may affect Gastric pH ........................................ 51 
 
Study Restrictions.................................................................................................. 52 
7 
STUDY ASSESSMENTS AND PROCEDURES ........................................................ 53 
7.1 
Efficacy Assessments .................................................................................................... 53 
 
Eczema Area and Severity Index ........................................................................... 53 
 
Investigator Global Assessment ............................................................................ 53 
 
SCORing Atopic Dermatitis .................................................................................. 53 
 
Body Surface Area ................................................................................................ 53 
 
Pruritus Numeric Rating Scale ............................................................................. 54 
 
5-D Pruritus Scale ................................................................................................ 54 
7.2 
Quality-of-Life Assessments ......................................................................................... 54 
 
Patient-Oriented Eczema Measure ....................................................................... 54 
 
Dermatology Life Quality Index Questionnaire ................................................... 54 
7.3 
Safety Assessments ....................................................................................................... 55 
 
Vital Signs ............................................................................................................. 55 
 
Physical Examination ........................................................................................... 55 
 
Brief Physical Examination .................................................................................. 55 
 
Clinical Laboratory Tests ..................................................................................... 56 
 
Electrocardiogram ................................................................................................ 58 
7.4 
Pharmacokinetic Assessment ........................................................................................ 58 


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7.5 
Adverse Events and Serious Adverse Events ............................................................... 59 
 
Definition of Adverse Event .................................................................................. 59 
 
Definition of Treatment-Emergent Adverse Event ................................................ 59 
 
Definition of Serious Adverse Event ..................................................................... 59 
 
Classification of an Adverse Event ....................................................................... 60 
 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 61 
 
Adverse Event Reporting....................................................................................... 62 
 
Serious Adverse Events Reporting ........................................................................ 62 
 
Pregnancy Reporting ............................................................................................ 62 
 
Overdose ............................................................................................................... 63 
8 
STATISTICAL CONSIDERATIONS .......................................................................... 64 
8.1 
Sample Size Determination ........................................................................................... 64 
8.2 
Populations for Analyses .............................................................................................. 64 
8.3 
Statistical Analyses ....................................................................................................... 64 
 
General Approach ................................................................................................. 64 
 
Safety Analyses...................................................................................................... 64 
 
Efficacy Analyses .................................................................................................. 65 
 
Pharmacokinetic Analyses .................................................................................... 66 
 
Other Analyses ...................................................................................................... 66 
 
Planned Interim Analysis ...................................................................................... 66 
9 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS .... 67 
9.1 
Local Regulations/Declaration of Helsinki ................................................................... 67 
9.2 
Ethical Review .............................................................................................................. 67 
9.3 
Informed Consent Process ............................................................................................ 67 
9.4 
Study Discontinuation and Closure ............................................................................... 68 
9.5 
Confidentiality and Privacy .......................................................................................... 68 
9.6 
Clinical Monitoring ....................................................................................................... 69 
9.7 
Quality Assurance and Quality Control ........................................................................ 69 
9.8 
Data Handling and Record Keeping ............................................................................. 69 
9.9 
Protocol Deviations ....................................................................................................... 70 
9.10 
Publication Policy ......................................................................................................... 70 
10 
REFERENCES .............................................................................................................. 71 
APPENDIX A: Eczema Area and Severity Index ........................................................................ 73 
APPENDIX B: vIGA-ADTM ......................................................................................................... 74 
APPENDIX C: Scoring Atopic Dermatitis - SCORAD ............................................................... 75 
APPENDIX D: 5-D Pruritus Scale ............................................................................................... 76 


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APPENDIX E: Patient-Oriented Eczema Measure ...................................................................... 77 
APPENDIX F: Dermatology Life Quality Index.......................................................................... 78 
 
LIST OF TABLES 
 
Table 1: Schedule of Events ......................................................................................................... 26 
Table 2. Study Products ................................................................................................................ 47 
Table 3: Dose assignment for subjects who participated in the preceding ASN002AD-201 study
....................................................................................................................................................... 49 
Table 4. Prohibited Therapies or Procedures ................................................................................ 51 
Table 5. Examples of H2 antagonists and Proton Pump Inhibitors .............................................. 52 
Table 6: Clinical Laboratory Testing ............................................................................................ 57 
 
LIST OF FIGURES 
 
Figure 1: Study Diagram ............................................................................................................... 25 
Figure 2: Pruritus Numeric Rating Scale ...................................................................................... 54 
 
 
 
 
 




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-To implement a discontinuation 
criterion 
regarding 
ineffective 
treatment during the study.  
 
-Section 
5.3.1, 
the 
following 
discontinuation criterion was added: 
 
"The subject is not receiving benefit 
from the study drug. If, at any time 
during 
the 
study, 
either 
the 
Investigator or the subject determines 
there is no clinical or symptomatic 
benefit from receiving continued 
treatment with the study drug, the 
Investigator must discuss alternative 
treatment options that are available to 
the subject." 
 
 
 
 
 
 
 


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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 
bid 
twice a day 
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 


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ITT 
intent-to-treat (population) 
IV 
intravenous 
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 
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 Phase 2, Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety, Tolerability, 
and Efficacy of ASN002 in Subjects with Moderate to Severe Atopic Dermatitis 
Phase of Development:  
Phase 2  
Study Center(s):  
Approximately 50 study centers located in the United States, Canada, and Germany will participate in 
this study.  
Number of Subjects (planned):  
This study is open to the subjects who participated in one of the preceding studies on ASN002  
(ASN002AD-101 and ASN002AD-201). Therefore, it is anticipated that approximately 256 subjects will 
be included in this study. The actual sample size will depend on the number of subjects transitioning 
from prior ASN002 studies, so the anticipated number is not proposed as a fixed enrollment goal. 
Duration of Study:  
The maximum study duration per subject is up to 110 weeks (including up to 4 weeks for the screening 
period, up to 104 weeks (24 months) for the treatment period and a 2-week follow-up period).  
Investigational Product, Dosage, and Mode of Administration:  
ASN002 40, 60, or 80 mg orally administered once daily for up to 24 months. ASN002 will be 
available in 20-mg strength tablets. 
Objectives: 
Primary: 
• To evaluate the long-term safety and tolerability of ASN002 in subjects with moderate to severe 
atopic dermatitis (AD) who have participated in one of the preceding studies (ASN002AD-101 and 
ASN002AD-201)  
Secondary: 
• To evaluate the long-term efficacy of ASN002 in subjects with moderate to severe AD who have 
participated in one of the preceding studies (ASN002AD-101 and ASN002AD-201) 
• To evaluate the effect of dose reduction at randomization in responder subjects with moderate to 
severe AD treated with ASN002 at 60 mg or 80 mg in study ASN002AD-201 
• To evaluate the effect of dose increase at randomization in non-responder subjects with moderate 
to severe AD treated with ASN002 at 40 mg or 60 mg in study ASN002AD-201 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
• To assess population PK of ASN002 in AD subjects via a population PK analysis approach 
Exploratory: 
• To explore the relationships between PK exposure and clinical measurement (e.g., efficacy and 
safety) as appropriate 
Endpoints: 
Primary Endpoint: 
• Number and rate (events per 100 patient-years) of treatment-emergent adverse events (TEAEs)  
Secondary Endpoints: 
Secondary safety endpoints include: 
• Number and rate (events per 100 patient-years) of drug-related TEAEs  
• Proportion of subjects withdrawing from worsening AD at each visit 
• Changes in vital signs, physical examinations, electrocardiogram (ECG), and safety laboratory 
tests 
Secondary efficacy endpoints include: 
• Change and percent change from baseline in Eczema Area and Severity Index (EASI) score at each 
visit 
• Proportion of subjects with at least a 50% reduction from baseline in EASI (EASI50) at each visit 
• Proportion of subjects achieving at least a 75% reduction from baseline in EASI (EASI75) at each 
visit  
• Proportion of subjects achieving at least a 90% reduction from baseline in EASI (EASI90) at each 
visit 
• Time to achieve EASI50, EASI75, and EASI90 relative to baseline only in subjects who received 
the placebo in the previous study  
• Proportion of subjects maintaining EASI75 in responder subjects in ASN002AD-201 randomized 
to a reduced dose of ASN002 in ASN002AD-201-EXT 
• Proportion of subjects achieving EASI75 in non-responder subjects in ASN002AD-201 
randomized to an increased dose of ASN002 in ASN002AD-201-EXT 
• 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 each visit 
• Proportion of subjects achieving at least a 2-grade reduction from baseline in IGA at each visit 
• Proportion of subjects achieving an IGA of clear (0) or almost clear (1) at each visit 
• Change from baseline in SCORing Atopic Dermatitis (SCORAD) at each visit 
• Change from baseline in 5-D Pruritus Scale at each visit 
• Change and percent change from baseline in pruritus Numeric Rating Scale (NRS) at each visit 
• Proportion of subjects achieving at least a 4-point reduction from baseline in pruritus NRS at each 
visit 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
• Change and percent change from baseline in Body Surface Area (BSA) involved with AD at each 
visit 
• Change from baseline in Patient-Oriented Eczema Measure (POEM) at each visit 
• Change from baseline in Dermatology Life Quality Index (DLQI) at each visit 
• Number and percentage of subjects with dose increase after randomization in the present study  
• Time to first AD flare 
Secondary PK endpoint includes: 
• Measurement of plasma concentrations of ASN002 
Exploratory Endpoints: 
Exploratory endpoints include: 
• Characterization of population PK parameters via nonlinear mixed-effects modeling 
• Characterization of the relationship between PK exposure and efficacy and safety parameters  
 
Study Design: 
This is a Phase 2, multicenter, open-label extension (OLE) study designed to investigate the long-term 
safety, tolerability, efficacy, and pharmacokinetics of ASN002 in the treatment of moderate to severe 
AD. 
Approximately 256 subjects with AD who participated in one of the preceding studies on ASN002 
(ASN002AD-101 and ASN002AD-201) will be included in this study. Subjects will be eligible to enter 
the OLE study if they (1) participated in ASN002AD-101 study OR (2) participated in ASN002AD-201 
study, completed at least the first 4 weeks without the use of prohibited treatments for AD, and completed 
the study visits up to Week 12 (subjects who started prohibited systemic medication and who had the 
study product discontinued in ASN002AD-201 study are allowed to enroll in the OLE study but not 
earlier than 12 weeks after Day 1 of the ASN002AD-201 study). Subjects who received the placebo in 
the other preceding studies are allowed to be enrolled in the OLE study. However, subjects who received 
the placebo in the study ASN002AD-201 will not be allowed to enter in the OLE study directly if they 
were responders at Week 12 based on EASI75. Placebo responders will be allowed to enter in the OLE 
study only if they have a flare within 2 months after their Week 12 visit, unless agreed to in writing by 
the Sponsor.  
All subjects will sign an informed consent specific for the OLE study before initiating any trial-related 
procedures. Subjects will be eligible for study enrollment if he/she meets all inclusion criteria and none 
of the exclusion criteria. 
For subjects who participated in the preceding ASN002AD-201 study, Day 1 visit should preferably 
occur on the same day of the Week 12 visit of the preceding study (or at least 12 weeks after Day 1 of 
ASN002AD-201 study for subjects who started prohibited systemic medications) or can be delayed up 
to 2 weeks after, if needed, to minimize treatment interruption. In both cases, subjects will not have to 
perform the Screening visit in the OLE study, and assessments that are common to both visits (Screening 
and Day 1 visits) will be performed only once. If the Week 12 visit of the preceding ASN002AD-201 
study and Day 1 of the OLE study are performed on the same day, assessments that are common to both 
visits will be performed also only once.  All subjects from the preceding ASN002AD-201 study who are 




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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
Efficacy will be assessed using IGA, EASI, SCORAD, BSA, pruritus NRS, and 5-D pruritus scale. 
Quality of life will be evaluated using POEM and DLQI.  
ASN002 exposure will be monitored via sparse PK samples (trough and 3-hour post-dose samples) on 
the study visits. Exposure-response relationships between ASN002 exposure and selected safety and 
efficacy data may be explored. 
Inclusion/Exclusion Criteria: 
For subjects who participated in the preceding ASN002AD-201 study and for which the Day 1 visit 
is performed on the same day as Week 12 visit or up to 2 weeks after, the following inclusion and 
exclusion criteria will be applied at Day 1: 
Inclusion criteria: 
In order to be eligible to participate in this study, a subject must meet all of the following criteria at 
Day 1 visit, unless specified otherwise:  
1. Subject with a history of moderate to severe atopic dermatitis who participated in the preceding 
ASN002AD-201 study, who completed at least the first 4 weeks without the use of prohibited 
treatments for AD, and completed the study visits up to Week 12. 
2. Subject must be a candidate for prolonged open label ASN002 treatment according to the 
investigator’s judgment. 
3. Subject has been using an emollient (except those containing urea) daily for at least 1 week prior to 
Day 1 and agrees to continue using that same emollient daily throughout the study. Note: On the day 
of scheduled visits, subjects cannot apply emollient before their scheduled visit time.   
4. For women of childbearing potential involved in any sexual intercourse that could lead to pregnancy: 
the subject must agree to continue using a highly effective contraceptive method 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 of the preceding ASN002AD-201 study and will continue to be abstinent 
from penile-vaginal intercourse throughout the OLE 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); 


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Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
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). FSH testing not 
required if already performed in the preceding study (data is available on file) and confirmed 
nonchildbearing potential. 
5. 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 #4, from Day 1 until 
at least 90 days 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 of the preceding ASN002AD-201 study 
until at least 90 days after the last study product administration of the present study. 
6. Female of childbearing potential has had a negative urine pregnancy test at Day 1.  
7. Subject is willing to participate and is capable of giving informed consent. Note: Consent must be 
obtained prior to any study-related procedures. 
8. Subjects must be willing to comply with all study procedures and must be available for the duration 
of the study. 
Exclusion criteria: 
 
A subject who meets any of the following criteria at the Day 1 visit, 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/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 a history of congestive heart failure New York Heart Association (NYHA) class III or 
IV. 
8. 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 
9. 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. 
10. Subject has a history of recurrent venous thromboembolic event (VTE) (>=2) 
11. 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. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
12. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned during 
the study. 
13. Subject is known to have immune deficiency or is immunocompromised. 
14. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
15. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 
16. Subject has a known history of diverticulitis. 
17. Subject has uncontrolled diabetes. 
18. 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. 
19. Subject has used dupilumab within 12 weeks prior to Day 1.  
20. Subject has used doxepin within 1 week prior to Day 1. 
21. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
22. Subject has used topical products containing urea within 1 week prior to Day 1. 
23. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior to 
Day 1. 
24. Subject has used oral corticosteroids for the treatment of AD within 2 weeks prior to Day 1.  
25. Subject has used systemic treatments (other than biologics and oral corticosteroids) that could affect 
atopic dermatitis less than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, 
methotrexate, 
cyclosporine, 
hydroxycarbamide 
[hydroxyurea], 
azathioprine, 
injectable 
corticosteroids). Note: Intranasal corticosteroids, eye drops containing corticosteroids, and inhaled 
corticosteroids for stable medical conditions are allowed.  
26. Subject has received any marketed or investigational biological agent targeting the immune system 
or that could have an effect on the immune system within 12 weeks or 5 half-lives (whichever is 
longer) prior to Day 1. 
27. Subject is currently receiving any other systemic medication for AD. 
28. Subject is currently receiving a nonbiological investigational product, other than ASN002, or device 
or has received one within 4 weeks prior to Day 1. 
29. 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.  
30. Subject had prior treatment with a systemic SYK or JAK inhibitor, other than ASN002, 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. 
31. Subject was withdrawn from the preceding study for which ASN002 has been stopped for safety 
reasons. 
32. Subject has a known hypersensitivity to ASN002 or its excipients. 
33. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to 
Day 1. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
34. 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. 
35. Subject is institutionalized because of legal or regulatory order. 
36. Subject is a placebo responder at Week 12 based on EASI75 in preceding study ASN002AD-201. 
Subject will be allowed to enter the OLE only if a flare occurs within 2 months following Week 12 
visit of the preceding study.  
For subjects who participated in the preceding ASN002AD-101 study and for subjects who 
participated in the preceding ASN002AD-201 study but are enrolled more than 2 weeks after their 
Week 12 visit, the following inclusion and exclusion criteria will be applied at the Screening and 
Day 1 visits: 
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. Subject with a history of moderate to severe atopic dermatitis who: 
a. participated in ASN002AD-101 study  
OR 
b. participated in ASN002AD-201 study, completed at least the first 4 weeks without the use 
of prohibited treatments for AD, and completed the study visits up to Week 12 (subjects who 
started prohibited systemic medication and who had the study product discontinued in 
ASN002AD-201 study are allowed to enroll in the OLE study but not earlier than 12 weeks 
after Day 1 of the ASN002AD-201 study). 
2. For subjects who participated in the preceding ASN002AD-101 study only: Subject has an EASI 
score ≥ 16 at Day 1. 
3. For subjects who participated in the preceding ASN002AD-101 study only: Subject has moderate to 
severe atopic dermatitis at Day 1, as defined by an IGA ≥ 3. 
4. For subjects who participated in the preceding ASN002AD-101 study only: Subject has atopic 
dermatitis covering ≥ 10% of the BSA on Day 1. 
5. Subject must be a candidate for prolonged open label ASN002 treatment according to the 
investigator’s judgment. 
6. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
7. Subject has been using an emollient (except those containing urea) daily for at least 1 week prior to 
Day 1 and agrees to continue using that same emollient daily throughout the study. Note: On the day 
of scheduled visits, subjects cannot apply emollient before their scheduled visit time.   
8. 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.  


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
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). FSH testing not 
required if already performed in the preceding study (data is available on file) and confirmed 
nonchildbearing potential. 
9. 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 #8, from Day 1 until 
at least 90 days 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 90 days after the last study 
product administration. 
10. Female of childbearing potential has had a negative serum pregnancy test at screening and negative 
urine pregnancy test at Day 1.  
11. Subject is willing to participate and is capable of giving informed consent. Note: Consent must be 
obtained prior to any study-related procedures. 
12. Subjects must be willing to comply with all study procedures and must be available for the duration 
of the study. 
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. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
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. If not performed within 1 year prior to Screening visit: 
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. If not performed within 1 year prior to Screening visit: 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
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 used doxepin within 1 week prior to Day 1. 
26. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
27. Subject has used topical products containing urea within 1 week prior to Day 1. 
28. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior to 
Day 1. 
29. Subject has used oral corticosteroids for the treatment of AD within 2 weeks prior to Day 1.  
30. Subject has used systemic treatments (other than biologics and oral corticosteroids) that could affect 
atopic dermatitis less than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, 
methotrexate, 
cyclosporine, 
hydroxycarbamide 
[hydroxyurea], 
azathioprine, 
injectable 
corticosteroids). Note: Intranasal corticosteroids, eye drops containing corticosteroids, and inhaled 
corticosteroids for stable medical conditions are allowed.  
31. Subject has received any marketed or investigational biological agent targeting the immune system 
or that could have an effect on the immune system within 12 weeks or 5 half-lives (whichever is 
longer) prior to Day 1. 
32. Subject is currently receiving any other systemic medication for AD. 
33. Subject is currently receiving a nonbiological investigational product, other than ASN002, or device 
or has received one within 4 weeks prior to Day 1. 
34. 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.  
35. Subject had prior treatment with a systemic SYK or JAK inhibitor, other than ASN002, 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. 
36. Subject was withdrawn from the preceding study for which ASN002 has been stopped for safety 
reasons. 
37. Subject has a known hypersensitivity to ASN002 or its excipients. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Name of Sponsor/Company:  
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
38. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to 
Day 1. 
39. 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. 
40. Subject is institutionalized because of legal or regulatory order. 
41. Subject is a placebo responder at Week 12 based on EASI75 in preceding study ASN002AD-201. 
Subject will be allowed to enter the OLE only if a flare occurs within 2 months following Week 12 
visit of the preceding study.  
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. 
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. The treatment group for safety will be determined as the last 
dose received prior to the AEs or prior to the safety results. Thus, a subject may be assigned to more than 
one treatment group, depending on the safety results assessed. 
Efficacy Analyses: 
The efficacy endpoints will be summarized with descriptive statistics for each treatment group. All 
subjects will be analyzed according to the treatment group to which they were initially randomized at 
the start of the OLE study (regardless of dose increase after randomization during the study). 
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.  
PK-efficacy and PK-safety relationships will be explored.  
Sample Size Consideration:  
No formal sample size or power calculations were performed for this study. The sample size is based on 
the completion of the preceding ASN002AD-101 and ASN002AD-201 studies and the consenting for 
the extension. 


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1.2 Study Diagram 
Figure 1: Study Diagram 
 
1.3 Schedule of Events 
All subjects will sign an informed consent specific for the OLE study before initiating any trial-
related procedures. Subject will be eligible for study enrollment if he/she meets all inclusion 
criteria and none of the exclusion criteria.  
For subjects who participated in the preceding ASN002AD-201 study, Day 1 visit should 
preferably occur on the same day of the Week 12 visit of the preceding study or can be delayed up 
to 2 weeks after, if needed, to minimize treatment interruption. In both cases, subjects will not 
have to perform the Screening visit in the OLE study, and assessments that are common to both 
visits (Screening and Day 1 visits) will be performed only once. If the Week 12 visit of the 
preceding ASN002AD-201 study and Day 1 of the OLE study are performed on the same day, 
assessments that are common to both visits will be performed also only once.  All subjects from 
the preceding ASN002AD-201 study who are enrolled in the OLE study more than 2 weeks after 
their Week 12 visit will have to perform a complete screening evaluation no more than 30 days 
prior to Day 1. The Screening visit should not be performed more than 2 months after the subject’s 
Week 12 visit for subjects who participated in the ASN002AD-201 study, unless agreed to in 
writing by the Sponsor. 
Subjects who participated in the preceding ASN002AD-101 study will have to perform the 
Screening visit. Enrolment of subjects who participated in the preceding ASN002AD-101 study 
will be allowed until the last subject from the ASN002AD-201 study has performed his Week 12 
visit.  
For subjects who have to perform the Screening visit, the Day 1 visit must occur, at the latest, 
30 days after the Screening visit.  
Table 1 provides a description of the procedures to be performed at each visit. Unless specified 
otherwise, the study assessments scheduled during the study visits will be performed before the 
study drug administration. If assessments are scheduled at the same time, then the assessments 
should occur in the following order: 






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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 studies with ASN002 


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provide strong rationale for its evaluation in subjects with atopic dermatitis. In the 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 Phase 1b clinical trial (ASN002AD-101), ASN002 has showed significant benefit 
for the treatment of atopic dermatitis, especially at 40 mg and 80 mg once-daily dosing regimens. 
A Phase 2b study (ASN002D-201) is currently ongoing to further investigate the benefit and risk 
of ASN002 at 40 mg, 60 mg and 80 mg once-daily dosing regimens 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. 
 
This trial is to collect long-term data on ASN002. The primary objective of this study is to assess 
the long-term safety and tolerability of ASN002 in subjects with moderate to severe AD who have 
participated in one of the preceding studies (ASN002AD-101 and ASN002AD-201). Long-term 
efficacy of ASN002 will also be evaluated as secondary endpoints. The doses to be administered 
in this study range between 40 and 80 mg, which were found to be well tolerated and safe in the 
previous Phase 1b study. Adverse events observed in the Phase 1b 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. 


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2.2 Risk/Benefit Assessment 
 Known Potential Risks 
The data from both nonclinical and clinical studies with ASN002 suggest that it is anticipated to 
be safe and well-tolerated at the doses to be administered in the present study.  
 
In cancer subjects, ASN002 has been studied at daily doses up to 100 mg bid. 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 has also been studied in a safety, tolerability, PK, and food effect study in 
healthy subjects at doses up to a single oral dose of 100 mg. The most common adverse event in 
this study was headache. One SAE, premature ventricular contractions, which was asymptomatic 
and mild, was experienced by one subject dosed with 50 mg ASN002 once. It 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 1b study in AD patients. Adverse 
events observed in the Phase 1b study were mild or moderate at daily doses up to 80 mg for 
4 weeks.  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 
Based on the Phase 1b clinical trial (ASN002AD-101), it is anticipated that subjects will benefit 
from the long-term treatment with ASN002 as a result of participating in this study. 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 following the long-term 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 (sites who participated in preceding studies on ASN002, i.e. ASN002AD-
101 and ASN002AD-201). 
This is a Phase 2, multicenter, open-label extension (OLE) study designed to investigate the 
long-term safety, tolerability, efficacy, and pharmacokinetics of ASN002 in the treatment of 
moderate to severe AD. 
Approximately 256 subjects with AD who participated in one of the preceding studies on ASN002 
(ASN002AD-101 and ASN002AD-201) will be included in this study. Subjects will be eligible to 
enter the OLE study if they (1) participated in ASN002AD-101 study OR (2) participated in 
ASN002AD-201 study, completed at least the first 4 weeks without the use of prohibited 
treatments for AD, and completed the study visits up to Week 12 (subjects who started prohibited 
systemic medication and who had the study product discontinued in ASN002AD-201 study are 
allowed to enroll in the OLE study but not earlier than 12 weeks after Day 1 of the ASN002AD-
201 study). Subjects who received the placebo in the other preceding studies are allowed to be 
enrolled in the OLE study. However, subjects who received the placebo in the study ASN002AD-
201 will not be allowed to enter in the OLE study directly if they were responders at Week 12 
based on EASI75. Placebo responders will be allowed to enter in the OLE study only if they have 
a flare within 2 months after their Week 12 visit, unless agreed to in writing by the Sponsor. 
All subjects will sign an informed consent specific for the OLE study before initiating any trial-
related procedures. Subjects will be eligible for study enrollment if he/she meets all inclusion 
criteria and none of the exclusion criteria. 
For subjects who participated in the preceding ASN002AD-201 study, Day 1 visit should 
preferably occur on the same day of the Week 12 visit of the preceding study (or at least 12 weeks 
after Day 1 of ASN002AD-201 study for subjects who started prohibited systemic medications) 
or can be delayed up to 2 weeks after, if needed, to minimize treatment interruption. In both cases, 
subjects will not have to perform the Screening visit in the OLE study, and assessments that are 
common to both visits (Screening and Day 1 visits) will be performed only once. If the Week 12 
visit of the preceding ASN002AD-201 study and Day 1 of the OLE study are performed on the 
same day, assessments that are common to both visits will be performed also only once.  All 
subjects from the preceding ASN002AD-201 study who are enrolled in the OLE study more than 
2 weeks after their Week 12 visit will have to perform a complete screening evaluation no more 
than 30 days prior to Day 1. The Screening visit should not be performed more than 2 months after 
the subject’s Week 12 visit for subjects who participated in the ASN002AD-201 study, unless 
agreed to in writing by the Sponsor. 
Subjects who participated in the preceding ASN002AD-101 study will have to perform the 
Screening visit. Enrolment of subjects who participated in the preceding ASN002AD-101 study 
will be allowed until the last subject from the ASN002AD-201 study has performed his Week 12 
visit.  


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Eligible subjects will be randomized on Day 1 to receive ASN002 once daily for up to 24 months. 
After 12 months of ASN002 study treatment, study treatment may be extended to 24 months 
contingent on Sponsor’s decision based on emerging ASN002 clinical trial data. 
For scheduled study visits, subjects will come to the study center up to 12 occasions: Screening; 
Day 1; Months 1, 3, 6, 9, 12, 15, 18, 21, 24, and Follow-up/Early Termination (ET). For subjects 
who participated in the preceding ASN002AD-201 study and are enrolled in the OLE study within 
2 weeks after their Week 12 visit, the Screening visit will not be performed, and they will come to 
the study center for up to 11 visits (the assessments that are common to both visits will be 
performed only once at Day 1). 
Safety will be assessed by adverse events (AEs), physical examination, vital signs, 12-lead ECG, 
and clinical laboratory tests. 
Efficacy will be assessed using IGA, EASI, SCORAD, BSA, pruritus NRS, and 5-D pruritus scale. 
Quality of life will be evaluated using POEM and DLQI.  
ASN002 exposure will be monitored via sparse PK samples (trough and 3-hour post-dose samples) 
on the study visits. Exposure-response relationships between ASN002 exposure and selected 
safety and efficacy data may be explored. 
No formal interim analyses are planned for this open-label study, except for the review of safety 
data on regular basis.   
4.2 Scientific Rationale for Study Design  
The proposed design is considered appropriate for assessing the long-term safety and tolerability 
and to evaluate the long-term efficacy of ASN002 study product in subjects with atopic dermatitis. 
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. 
 
The end of the study is defined as completion of the last visit or procedure shown in the schedule 
of event for the last enrolled subject in the trial globally for all sites. 
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 


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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 patient’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. 
 
Dose adjustment is not permitted other than as defined in the present protocol, as described in 
Section 6.3. 
 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 that 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 Safety Monitoring  
The primary medical monitor and sponsor clinical team will review the safety data on a regular 
basis. An independent Data and Safety Monitoring Board (DSMB) is not required for the study. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
However, recommendations of the DSMB during the ASN002AD-201 study that are applicable to 
the present OLE study will be applied, as needed. 
 
 


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5 
STUDY POPULATION  
5.1 Inclusion Criteria 
For subjects who participated in the preceding ASN002AD-201 study and for which the 
Day 1 visit is performed on the same day as Week 12 visit or up to 2 weeks after, the following 
inclusion criteria will be applied at Day 1: 
In order to be eligible to participate in this study, a subject must meet all of the following criteria 
at Day 1 visit, unless specified otherwise:  
1. Subject with a history of moderate to severe atopic dermatitis who participated in the preceding 
ASN002AD-201 study, who completed at least the first 4 weeks of treatment without the use 
of prohibited treatments for AD, and completed the study visits up to Week 12. 
2. Subject must be a candidate for prolonged open label ASN002 treatment according to the 
investigator’s judgment. 
3. Subject has been using an emollient (except those containing urea) daily for at least 1 week 
prior to Day 1 and agrees to continue using that same emollient daily throughout the study. 
Note: On the day of scheduled visits, subjects cannot apply emollient before their scheduled 
visit time.   
4. For women of childbearing potential involved in any sexual intercourse that could lead to 
pregnancy: the subject must agree to continue using a highly effective contraceptive method 
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 of the preceding ASN002AD-201 study and will continue to be 
abstinent from penile-vaginal intercourse throughout the OLE 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 


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levels). FSH testing not required if already performed in the preceding study (data 
is available on file) and confirmed nonchildbearing potential. 
5. 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 #4, from 
Day 1 until at least 90 days 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 of the preceding 
ASN002AD-201 study until at least 90 days after the last study product administration of the 
present study. 
6. Female of childbearing potential has had a negative urine pregnancy test at Day 1.  
7. Subject is willing to participate and is capable of giving informed consent. Note: Consent must 
be obtained prior to any study-related procedures. 
8. Subjects must be willing to comply with all study procedures and must be available for the 
duration of the study. 
For subjects who participated in the preceding ASN002AD-101 study and for subjects who 
participated in the preceding ASN002AD-201 study but are enrolled more than 2 weeks after 
their Week 12 visit, the following inclusion criteria will be applied at the Screening and Day 1 
visits: 
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. Subject with a history of moderate to severe atopic dermatitis who: 
a. participated in ASN002AD-101 study  
OR 
b. participated in ASN002AD-201 study, completed at least the first 4 weeks without 
the use of prohibited treatments for AD, and completed the study visits up to 
Week 12 (subjects who started prohibited systemic medication and who had the 
study product discontinued in ASN002AD-201 study are allowed to enroll in the 
OLE study but not earlier than 12 weeks after Day 1 of the ASN002AD-201 study). 
2. For subjects who participated in the preceding ASN002AD-101 study only: Subject has an 
EASI score ≥ 16 at Day 1. 
3. For subjects who participated in the preceding ASN002AD-101 study only: Subject has 
moderate to severe atopic dermatitis at Day 1, as defined by an IGA ≥ 3. 
4. For subjects who participated in the preceding ASN002AD-101 study only: Subject has atopic 
dermatitis covering ≥ 10% of the BSA on Day 1. 
5. Subject must be a candidate for prolonged open label ASN002 treatment according to the 
investigator’s judgment. 
6. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
7. Subject has been using an emollient (except those containing urea) daily for at least 1 week 
prior to Day 1 and agrees to continue using that same emollient daily throughout the study. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
Note: On the day of scheduled visits, subjects cannot apply emollient before their scheduled 
visit time.   
8. 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). FSH testing not required if already performed in the preceding study (data 
is available on file) and confirmed nonchildbearing potential. 
9. 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 #8, from 
Day 1 until at least 90 days 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 90 
days after the last study product administration. 
10. Female of childbearing potential has had a negative serum pregnancy test at screening and 
negative urine pregnancy test at Day 1.  
11. Subject is willing to participate and is capable of giving informed consent. Note: Consent must 
be obtained prior to any study-related procedures. 
12. Subjects must be willing to comply with all study procedures and must be available for the 
duration of the study. 


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5.2 Exclusion Criteria 
For subjects who participated in the preceding ASN002AD-201 study and for which the 
Day 1 visit is performed on the same day as Week 12 visit or up to 2 weeks after, the following 
exclusion criteria will be applied at Day 1: 
A subject who meets any of the following criteria at the Day 1 visit, 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/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 a history of congestive heart failure New York Heart Association (NYHA) class 
III or IV. 
8. 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 
9. 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. 
10. Subject has a history of recurrent venous thromboembolic event (VTE) (>=2) 
11. 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. 
12. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned 
during the study. 
13. Subject is known to have immune deficiency or is immunocompromised. 
14. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
15. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 
16. Subject has a known history of diverticulitis. 
17. Subject has uncontrolled diabetes. 


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18. 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. 
19. Subject has used dupilumab within 12 weeks prior to Day 1.  
20. Subject has used doxepin within 1 week prior to Day 1. 
21. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
22. Subject has used topical products containing urea within 1 week prior to Day 1. 
23. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior 
to Day 1. 
24. Subject has used oral corticosteroids for the treatment of AD within 2 weeks prior to Day 1. 
25. Subject has used systemic treatments (other than biologics and oral corticosteroids) that could 
affect atopic dermatitis less than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, 
methotrexate, cyclosporine, hydroxycarbamide [hydroxyurea], azathioprine, injectable 
corticosteroids). Note: Intranasal corticosteroids, eye drops containing corticosteroids, and 
inhaled corticosteroids for stable medical conditions are allowed.  
26. Subject has received any marketed or investigational biological agent targeting the immune 
system or that could have an effect on the immune system within 12 weeks or 5 half-lives 
(whichever is longer) prior to Day 1. 
27. Subject is currently receiving any other systemic medication for AD. 
28. Subject is currently receiving a nonbiological investigational product, other than ASN002, or 
device or has received one within 4 weeks prior to Day 1. 
29. 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.  
30. Subject had prior treatment with a systemic SYK or JAK inhibitor, other than ASN002, 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. 
31. Subject was withdrawn from the preceding study for which ASN002 has been stopped for 
safety reasons. 
32. Subject has a known hypersensitivity to ASN002 or its excipients. 
33. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior 
to Day 1. 
34. 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. 
35. Subject is institutionalized because of legal or regulatory order. 
36. Subject is a placebo responder at Week 12 based on EASI75 in preceding study ASN002AD-
201. Subject will be allowed to enter the OLE only if a flare occurs within 2 months following 
Week 12 visit of the preceding study.  


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For subjects who participated in the preceding ASN002AD-101 study and for subjects who 
participated in the preceding ASN002AD-201 study but are enrolled more than 2 weeks after 
their Week 12 visit, the following exclusion criteria will be applied at the Screening and Day 1 
visits: 
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. 
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. If not performed within 1 year prior to Screening visit: 


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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. If not performed within 1 year prior to Screening visit: 
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 used doxepin within 1 week prior to Day 1. 
26. Subject has used hydroxyzine or diphenhydramine within 1 week prior to Day 1.  
27. Subject has used topical products containing urea within 1 week prior to Day 1. 


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28. Subject has used systemic antibiotics within 2 weeks or topical antibiotics within 1 week prior 
to Day 1. 
29. Subject has used oral corticosteroids for the treatment of AD within 2 weeks prior to Day 1.  
30. Subject has used systemic treatments (other than biologics and oral corticosteroids) that could 
affect atopic dermatitis less than 4 weeks prior to Day 1 (e.g., retinoids, calcineurin inhibitors, 
methotrexate, cyclosporine, hydroxycarbamide [hydroxyurea], azathioprine, injectable 
corticosteroids). Note: Intranasal corticosteroids, eye drops containing corticosteroids, and 
inhaled corticosteroids for stable medical conditions are allowed.  
31. Subject has received any marketed or investigational biological agent targeting the immune 
system or that could have an effect on the immune system within 12 weeks or 5 half-lives 
(whichever is longer) prior to Day 1. 
32. Subject is currently receiving any other systemic medication for AD. 
33. Subject is currently receiving a nonbiological investigational product, other than ASN002, or 
device or has received one within 4 weeks prior to Day 1. 
34. 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.  
35. Subject had prior treatment with a systemic SYK or JAK inhibitor, other than ASN002, 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. 
36. Subject was withdrawn from the preceding study for which ASN002 has been stopped for 
safety reasons. 
37. Subject has a known hypersensitivity to ASN002 or its excipients. 
38. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior 
to Day 1. 
39. 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. 
40. Subject is institutionalized because of legal or regulatory order. 
41. Subject is a placebo responder at Week 12 based on EASI75 in preceding study ASN002AD-
201. Subject will be allowed to enter the OLE only if a flare occurs within 2 months following 
Week 12 visit of the preceding study.  
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 


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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.  
 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 discontinue will not be replaced.  
 
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. 
• 
The subject is not receiving benefit from the study drug. If, at any time during the study, either 
the Investigator or the subject determines there is no clinical or symptomatic benefit from 
receiving continued treatment with the study drug, the Investigator must discuss alternative 
treatment options that are available to the subject. 
 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.  


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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 
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. 
 
 
 




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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 may only be supplied by authorized site staff and may 
only be given to subjects enrolled into the study.   
 
The study product 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 study site, each eligible subject will be assigned a subject identifier number 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 based on chronological order of entering 
in the study (e.g., 002-010 for the 10th subject who entered in the study at the Site #002). 
 
Approximately 256 subjects will be randomized to receive either ASN002 40 mg, 60 mg, or 80 mg. 
 
Randomization will occur at Day 1 visit. The randomization list will be generated using a validated 
software. This list will be uploaded into an Interactive Web Response System (IWRS). The 




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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 the first study visit (Screening or Day 1) 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 
Topical medicated treatment for atopic dermatitis 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 are permitted during the 
study. Topical corticosteroids of class 5, 6, and 7 according to the American classification are 
allowed without any time restriction throughout the study. Topical corticosteroids of class 1, 2, 3, 
and 4 according to the American classification are only permitted for 2 short periods of time during 
the study (maximum of 2 weeks each time).  
 
Psoralen-UV-A (PUVA) treatment and any UV-B phototherapy (including tanning beds) or 
excimer laser are also permitted during the study. 
 
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 subjects must continue 
using it daily throughout the study. However, on the day of scheduled visits, subjects cannot apply 
emollient before their scheduled visit time.   
 
The commercial name of the selected emollient(s) will be recorded in the source document and the 
eCRF.  
Use of sunscreen products and protective apparel are permitted when sun exposure cannot be 
avoided.  
No other products except those listed above may be applied to the lesions during the study. 






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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, an effort will be made to have the same assessor 
perform all assessments on a given subject, whenever possible. 
 Eczema Area and Severity Index 
The 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 A.  
 Investigator Global Assessment 
The IGA 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 B.  
 SCORing Atopic Dermatitis  
The 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 for the AD severity. The overall BSA affected by 
AD will be evaluated (from 0% to 100%) and included in the SCORAD scores (refer to 
Section 7.1.4). 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 C.  
 Body Surface Area 
The overall 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 1% of his or her 
total BSA. For all study visits except at screening, the BSA of involved skin will be measured with 
the SCORAD measurement (Section 7.1.3) and evaluated as a separate endpoint.  




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multinational studies. The DLQI is the most frequently used instrument in studies of randomized 
controlled trials in dermatology. The questionnaire is provided in Appendix F. 
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). 
 
The weight (kg) and BMI will be recorded at the visits specified in Table 1. The height collected 
at the Screening visit of the preceding study will be used in the present study and does not need to 
be collected again.  The same value for the height will be used for BMI calculation at each visit. 
 
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. 
 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:  
 


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• 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), as applicable. 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 6. 
 




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 Electrocardiogram  
Twelve-lead ECGs will be performed as a safety assessment at the visits specified in Table 1. 
Clinically significant findings in the ECG should exclude a subject from study participation (as 
deemed appropriate by the investigator). Any significant change will be reported as an AE. 
7.4 Pharmacokinetic Assessment 
Blood samples will be collected for ASN002 exposure assessment on the study visits and time 
points indicated in the Schedule of Events in Table 1. 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. 
 
The PK concentration data from this study will be combined with the data from other ASN002 
clinical trials for population PK assessment. The population PK analysis plan and the results 
derived from the analysis are beyond the scope of this study and, thus, will be addressed separately.  
 
PK-efficacy and PK-safety relationships may be explored. The results from these analyses may be 
reported separately. 
 


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7.5 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 in the 
present study 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 
7.5.4.1 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. 
 
7.5.4.2 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. 


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7.5.4.3 Expectedness 
 
The expectedness of each SAE in relation to the study product will be determined in consultation 
with the Sponsor when necessary. 
 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, time 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 (this includes AEs that are ongoing at the last completed 
study visit of the preceding study). 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.   


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 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.  
 Serious Adverse Events Reporting 
 will be responsible for the overall pharmacovigilance process for this 
study. All SAEs, related to the experimental treatment or not, occurring during the course of the 
study must be reported on an SAE form to 
 (see below) within 24 hours of the knowledge of 
the occurrence (this refers to any AE that meets one or more of the aforementioned serious criteria). 
The SAE reporting period ends at the end of the follow-up period or if the subject begins an 
alternative therapy.  
 
Reporting should be done by sending the completed SAE form to the following e-mail address 
(faxing can also be done as a second option in case e-mailing is not possible).  
 
Safety Contact Information: 
 
E-mail: 
 
Fax: (
 
 
 will inform the sponsor, the primary medical monitor, and CRO within 1 business day of 
awareness of a new SAE. 
 will process and evaluate all SAEs as soon as the reports are 
received. For each SAE received, 
 will make a determination as to whether the criteria for 
expedited reporting to relevant regulatory authorities have been met. 
 will manage the AE 
reporting, including suspected unexpected serious adverse reactions, in accordance with the 
applicable local regulations. SAEs will be reported to the IRB/EC as per local IRB/EC 
requirements. 
 
The study sponsor will be responsible for notifying the Food and Drug Administration (FDA) of 
any unexpected fatal or life-threatening suspected adverse reactions as soon as possible, but in no 
case later than 7 calendar days after the sponsor's initial receipt of the information. In addition, the 
sponsor must notify the FDA and all participating investigators in an Investigational New Drug 
(IND) safety report of potential serious risks, from clinical trials or any other source, as soon as 
possible, but in no case later than 15 calendar days after the sponsor determines that the 
information qualifies for reporting. 
 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 
PPD
PPD
PPD


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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 7.5.7, 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 
No formal sample size or power calculations were performed for this study. The sample size is 
based on the completion of the preceding ASN002AD-101 and ASN002AD-201 studies and the 
consenting for the extension. 
8.2 Populations for Analyses 
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. 
 
Efficacy evaluable: This population will include all subjects who received at least one dose of the 
study product, have evaluable baseline and one post-dose assessment for at least one efficacy 
parameter. All subjects will be analyzed according to the treatment group that they initially 
received.  
 
The PK Population: This population will include all subjects who received at least one dose of 
ASN002 and have plasma concentration data. 
8.3 Statistical Analyses 
 General Approach 
Continuous variables will be summarized in tables and will include the number of subjects, mean, 
SD, CV%, median, minimum, and maximum. Categorical variables will be presented in tables as 
frequencies and percentages.  
 
The safety analysis will be done using the SAF population. The efficacy analysis will be done 
using the Efficacy Evaluable population. All efficacy analyses will be performed on observed case 
(i.e. without imputation of missing observations). 
 
Additional details regarding the efficacy and safety variable definitions, analyses strategy, and 
techniques for handling missing values will be detailed in a SAP that will be prepared before the 
database is locked and any analyses are undertaken.  
 Safety Analyses 
The treatment group for safety will be determined as the last dose received prior to the AEs or 
prior to the safety results. Thus, a subject may be assigned to more than one treatment group, 
depending on the safety results assessed. The safety summaries will be presented for 1) subjects 
who just started treatment (i.e. subjects from Phase 1b and subjects dosed on Placebo in Phase 2b) 


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and 2) for subjects who are continuing treatment (i.e. subjects treated with ASN002 in Phase 2b), 
separately. Additional safety analyses may be performed and will be described in the SAP.  
 
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. 
 Efficacy Analyses 
The efficacy endpoints will be summarized with descriptive statistics for each treatment group. 
All subjects will be analyzed according to the treatment group to which they were initially 
randomized at the start of the OLE study (regardless of dose increase after randomization during 
the study). 
 
Moreover, additional subgroup analyses will be described in the SAP (e.g. by responders and non-
responders within each dosing group). 


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 Pharmacokinetic Analyses 
ASN002 concentration data will be listed per subject and summarized descriptively per dose based 
on nominal times.  
 
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.  
 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 OLE study, except for the review of safety data on 
regular basis.   
 


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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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Confidential and proprietary. Permission should be obtained before any reproduction. 
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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Confidential and proprietary. Permission should be obtained before any reproduction. 
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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Confidential and proprietary. Permission should be obtained before any reproduction. 
classified into two separate categories: investigator’s study files and subject clinical source 
documents. 
 
The investigator must maintain source documents for each subject in the study. These source 
documents will consist of case and visit notes (clinical medical records) containing demographic 
and medical information and the results of any tests or assessments. All information on the eCRFs 
must be traceable to the source documents in the subject’s file. Data not requiring a written or 
electronic record will be defined before study start and will be recorded directly on the eCRFs, 
which will be documented as being the source data. 
The records should be retained by the investigator according to ICH guidelines, local regulations, 
or as specified in the Clinical Trial Agreement, whichever retention period is longer.  
 
Subject data will be entered by site personnel using 
, a web-based EDC and reporting 
system. This application will be set up for remote entry. 
 is the developer and owner 
of 
. The EDC software has been fully validated and conforms to Title 21 of the Code of 
Federal Regulations, Part 11 requirements. Investigator site staff will not be given access to the 
EDC system until they have been fully trained. Designated investigator staff will enter the data 
required by the protocol into the eCRFs using this web-based application. Automatic validation 
programs check for data discrepancies in the eCRFs and, by generating appropriate error messages, 
allow modification or verification of the entered data by the investigator staff before confirming 
the data. The investigator must certify that the data are complete and accurate by applying an 
electronic signature to the eCRFs.  
 
The data collected will be encoded and stored electronically in a database system. Validated data 
may subsequently be transferred to the sponsor. 
9.9 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
noncompliance may be either on the part of the subject, the investigator, or the study site staff. As 
a result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
Protocol deviations must be sent to the reviewing IRB/EC as per the IRB/EC requirements. 
9.10 Publication Policy 
The publication policy will be addressed in the Research and Financial Agreement, and all details 
outlined in the agreement will apply to this protocol. The trial will be registered on 
ClinicalTrials.Gov prior to the first subject being dosed. 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
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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Confidential and proprietary. Permission should be obtained before any reproduction. 
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. 
 
 
 


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Confidential and proprietary. Permission should be obtained before any reproduction. 
APPENDIX A: 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 B: vIGA-ADTM 
 


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APPENDIX C: 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 D: 5-D Pruritus Scale  
 


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APPENDIX E: 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 F: 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_001.pdf: 
 
 
Proprietary & Confidential 
Page 1 of 36 
 
Statistical Analysis Plan 
 
Study Title: 
A 
PHASE 
2, 
MULTICENTER, 
OPEN-LABEL 
EXTENSION STUDY TO EVALUATE THE LONG-
TERM SAFETY, TOLERABILITY AND EFFICACY 
OF ASN002 IN SUBJECTS WITH MODERATE TO 
SEVERE ATOPIC DERMATITIS 
Protocol Number and Version: 
ASN002AD-201-EXT V2.0 (Canada/US) dated 07 
February 2019 
Protocol Number and Version: 
ASN002AD-201-EXT V2.0 (Germany only) dated 07 
February 2019 
Product: 
ASN002 
Sponsor: 
Asana BioSciences, LLC 
 
  
  
  
 
Date: 
25-Feb-2020 
 
Version: 
Final 1.0 
 
Prepared by: 
 
 
 
 
 
 
 








 
STATISTICAL ANALYSIS PLAN, Version 
Final 1.0 
Protocol Number: ASN002AD-201-
EXT V2.0 
Sponsor: Asana BioSciences, LLC 
 
 
 
 Proprietary & Confidential 
Page 5 of 36 
 
8 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................ 21 
9 
SURGICAL AND MEDICAL HISTORY ........................................................................... 22 
10 
PRIOR AND CONCOMITANT MEDICATIONS ............................................................. 22 
11 
STUDY TREATMENT EXPOSURE AND TREATMENT COMPLIANCE ................. 23 
12 
EFFICACY ANALYSIS ........................................................................................................ 23 
12.1 
Efficacy Endpoints ......................................................................................................... 23 
13 
SAFETY ANALYSIS............................................................................................................. 29 
13.1 
Adverse Events ............................................................................................................... 29 
13.2 
Clinical Laboratory ........................................................................................................ 31 
13.3 
Vital Signs ....................................................................................................................... 31 
13.4 
Physical Examination .................................................................................................... 31 
13.5 
Electrocardiogram (ECG) ............................................................................................. 31 
14 
REFERENCES ....................................................................................................................... 33 
15 
APPENDICES ........................................................................................................................ 34 
 
 


STATISTICAL ANALYSIS PLAN, Version 
Final 1.0 
Protocol Number: ASN002AD-201-
EXT V2.0 
Sponsor: Asana BioSciences, LLC 
 
 
 
 Proprietary & Confidential 
Page 6 of 36 
 
ABBREVIATIONS 
AD 
Atopic Dermatitis 
AE 
adverse event 
ATC 
anatomical therapeutic chemical 
BMI 
body mass index 
BSA 
Body Surface Area 
bpm 
beats per minute 
CRF 
case report form 
CRO 
contract research organization 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
ECG 
Electrocardiogram 
eCRF  
electronic case report form  
EDC 
Electronic Data Capture 
ET 
early termination 
HR 
heart rate 
IGA 
Investigator’s Global Assessment 
IWRS 
Interactive Web Response System  
MedDRA  
Medical Dictionary for Regulatory Activities  
msec 
millisecond 
NRS 
Numeric Rating Scale 
OC 
Observed Cases 
POEM 
Patient Oriented Eczema Measure 
PK 
pharmacokinetic 
PT 
preferred term 
QTcF 
Fridericia’s correction formula for QT interval 
SAE  
serious adverse event  
SAP  
statistical analysis plan  
SAS 
statistical analysis system® 
SCORAD 
SCORing Atopic Dermatitis  
SD 
standard deviation 
SOC 
system organ class 
TEAE 
treatment emergent adverse event  
TLF 
tables, listings, and figures 
WHO-DD  
World Health Organization Drug Dictionary  
 




STATISTICAL ANALYSIS PLAN, Version 
Final 1.0 
Protocol Number: ASN002AD-201-
EXT V2.0 
Sponsor: Asana BioSciences, LLC 
 
 
 
 Proprietary & Confidential 
Page 8 of 36 
 
OBJECTIVES 
ENDPOINTS 
(ASN002AD-101 
and 
ASN002AD-201) 
• Proportion of subjects achieving at least a 75% reduction from 
baseline in EASI (EASI75) at each visit  
• Proportion of subjects achieving at least a 90% reduction from 
baseline in EASI (EASI90) at each visit 
• Time to achieve EASI50, EASI75, and EASI90 relative to baseline 
only in subjects who received the placebo in the previous study 
• 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 each visit 
• Proportion of subjects achieving at least a 2-grade reduction from 
baseline in IGA at each visit 
• Proportion of subjects achieving an IGA of clear (0) or almost clear 
(1) at each visit 
• Change from baseline in SCORing Atopic Dermatitis (SCORAD) 
at each visit 
• Change from baseline in 5-D Pruritus Scale at each visit 
• Change and percent change from baseline in pruritus Numeric 
Rating Scale (NRS) at each visit 
• Proportion of subjects achieving at least a 4-point reduction from 
baseline in pruritus NRS at each visit 
• Change and percent change from baseline in Body Surface Area 
(BSA) involved with AD at each visit 
• Change from baseline in Patient-Oriented Eczema Measure 
(POEM) at each visit 
• Change from baseline in Dermatology Life Quality Index (DLQI) 
at each visit 
• Number and percentage of subjects with dose increase after 
randomization in the present study 
• Time to first AD flare  
To evaluate the effect of 
dose reduction at 
randomization in 
responder subjects with 
moderate to severe AD 
treated with ASN002 at 
60 mg or 80 mg in study 
ASN002AD-201 
• Proportion of subjects maintaining EASI75 in responder subjects 
in ASN002AD-201 randomized to a reduced dose of ASN002 in 
ASN002AD-201-EXT 
 






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Safety will be assessed by adverse events (AEs), physical examination, vital signs, 12-lead ECG, 
and clinical laboratory tests. 
Efficacy will be assessed using IGA, EASI, SCORAD, BSA, pruritus NRS, and 5-D pruritus scale. 
Quality of life will be evaluated using POEM and DLQI.  
No formal interim analyses are planned for this open-label study, except for the review of safety 
data on regular basis.  
  
Figure 1: Study Diagram 
 
 
 
















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subjects starting ASN002, baseline is defined as the last nonmissing assessment prior to or on the 
first dose date of the open label extension and for subjects continuing ASN002 it is the last 
nonmissing assessment prior to or on the first dose date of the preceding study.  If the last 
nonmissing assessment is performed on the same date as the first study treatment and time is not 
available, the assessment will be considered as baseline, except for adverse events (AEs) and 
medications starting on the first study treatment dose date which will be considered post-baseline. 
5.3 Reference Start Date and Analysis Day 
Analysis day will be calculated from the first study treatment date and will be used to show 
start/end day of assessments or events.  
In the situation where the assessment/event date is partial or missing, analysis day will be 
missing. 
5.4 Windowing Conventions 
No windowing convention is followed for this study. 
5.5 Descriptive Statistics 
All continuous variables will be summarized by presenting the number of subjects, mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be presented as 
frequencies and percentages. Summary tables will be presented by treatment and visit, when 
applicable. 
Change from baseline will be calculated as:  
Assessment value at post-baseline visit X – baseline value. 
Percent change from baseline will be calculated as: 
(Assessment value at post-baseline visit X – baseline value) / baseline value * 100. 
5.6 Handling of Retests, Unscheduled Visits, and Early Termination Data 
When retests measurements are done, the retest measurement will be considered for the summary 
analysis. All data from retest visits will be listed. 
 
For safety data, unscheduled measurements will not be summarized in by-visit summary tables or 
figures. However, data from unscheduled visits will be listed. Early Termination (ET) visit 
assessments will be summarized as a separate visit in by-visit outputs. 


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5.7 Software Version 
All analyses will be performed using SAS® software Version 9.4 or higher. 
6 STATISTICAL CONSIDERATIONS 
6.1 Adjustments for Covariates 
N/A 
6.2 Handling of Dropouts or Missing data 
See Appendix 2 for handling of completely or partially missing dates for prior and concomitant 
medications and adverse events. 
No imputation of the data will be done and analyses will be conducted on the observed cases (OC).   
6.3 Interim Analysis and Data Monitoring 
No formal interim analyses are planned for this open-label study, except for the review of safety 
data on regular basis.   
6.4 Statistical Tests 
N/A 
7 STUDY SUBJECTS 
7.1 Disposition of Subjects 
All subjects who provide informed consent will be accounted for in this study. The number of 
subjects screened will be presented. Screen failures will be presented for all screened subjects 
Moreover, the number of subjects randomized included in each population will be presented. Study 
completion status and the reason for study discontinuation will also be presented. Percentages will 
be calculated using the number of subjects randomized as denominator. Number of days in the 
study will be calculated as follows and will be summarized: 
 
Number of days in study = Date of completion/discontinuation – 1st dose date +1 




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• Baseline SCORAD 
• Baseline DLQI 
• Baseline POEM 
The subject's demographic data, including date of birth, height, race, and ethnicity collected at the 
baseline of the preceding study will be used in the present study and do not need to be collected 
again. 
A listing of all demographics and baseline characteristics will be provided. 
9 SURGICAL AND MEDICAL HISTORY 
Medical and surgical history collected in the preceding study will be used in the present OLE 
study. Only new information and updates will need to be collected at Screening /Day 1 visit(s). 
Medical and surgical history will be coded according to the Medical Dictionary for Regulatory 
Activities (MedDRA), Version 21.0. 
Surgical and medical history will be summarized by system organ class (SOC) and preferred term 
(PT) using the safety population. A subject who experienced the same surgical and medical history 
event multiple times will be counted only once for the corresponding PT. Similarly, if a subject 
experienced multiple surgical and medical history events within the same SOC, the subject will be 
counted only once for that SOC. Surgical and medical history events will be sorted alphabetically 
by SOC and within each SOC the PT will be presented by decreasing order. 
A listing of all surgical and medical history events will be provided. 
10 PRIOR AND CONCOMITANT MEDICATIONS 
Medications will be coded according to the World Health Organization Drug Dictionary (WHO-
DD), March 2018 B2. 
Prior medications are defined as any medication started and discontinued prior to the first study 
treatment dose. Concomitant medications are defined as any medication taken after the first study 
treatment dose or taken prior to the first study treatment date and continued past that date. See 
Appendix 2 for handling of completely or partially missing dates for prior and concomitant 
medications.  


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Incidence of prior and concomitant medications will be tabulated by Anatomical Therapeutic 
Chemical Classification System, (ATC) level 2 and PT using the safety population. Subjects will 
be presented under the treatment group of the last dose received prior to the start of the medication. 
A subject with the same medication taken multiple times will be counted only once for the 
corresponding PT within a treatment group. Similarly, if a subject has taken more than one 
medication within the same ATC level, then the subject will be counted only once for that ATC 
within a treatment group.  
A listing of all prior and concomitant medications will be provided. 
11 STUDY TREATMENT EXPOSURE AND TREATMENT 
COMPLIANCE 
A summary of exposure will be presented using the safety population for each treatment group and 
will include descriptive statistics of the number of days treated for each treatment group. For each 
treatment, compliance will be calculated as follows: 
 
Number of doses  taken
Number of days between the last dose date and the first dose date +1 × 100 
 
Number of doses taken is obtained from IP accountability and for unreturned kits, the number of 
doses taken is assumed to be zero.  Descriptive statistics for the compliance will be presented for 
each treatment group. Frequency distribution will also be presented for the following categories: 
< 80%, [80% - 120%] and > 120%. A subject’s exposure and compliance will be counted and 
presented within each dose level received. 
 
Exposure and compliance will be displayed in a listing of study treatment administration. 
12 EFFICACY ANALYSIS 
As an abbreviated CSR will be provided due to early termination of the study, all efficacy analyses 
will be descriptive in nature. 
12.1 Efficacy Endpoints 
Eczema Area and Severity Index (EASI): 


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The EASI total score for 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. The score will be set to missing in case of at least one missing value.  
Descriptive statistics on EASI total score will be presented by visit for each treatment group. 
Change from baseline and percentage change from baseline will be also summarized. 
EASI score will be assessed as: 
• Change from baseline in EASI score at each available study visit 


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• Percent change from baseline in EASI score at each available study visit  
• Proportion of subjects achieving at least a 50% reduction from baseline in EASI 
(EASI50) at each available study visit 
•  Proportion of subjects achieving at least a 75% reduction from baseline in EASI 
(EASI75) at each available study visit 
• Proportion of subjects achieving at least a 90% reduction from baseline in EASI 
(EASI95) at each available study visit 
 
 
 


 
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Investigator Global Assessment (IGA): 
 
The Investigator Global Assessment (IGA) is a site-administered clinician-reported global 
assessment of the current state of the disease. It is measured on a 5-grade scale from 0 to 4, where 
0 = clear to 4 = severe. 
 
IGA will be assessed as  
• Proportion of subjects achieving at least a 2-grade reduction from baseline to clear 
(0) or almost clear (1) in IGA at each available study visit 
• Proportion of subjects achieving at least a 2-grade reduction from baseline in IGA 
at each available study visit 
• Proportion of subjects achieving an IGA of clear (0) or almost clear (1) at each 
available study visit 
 
SCORing Atopic Dermatitis (SCORAD): 
The Scoring Atopic Dermatitis (SCORAD) is built from six items (erythema, edema/papulation, 
oozing/crusts, excoriation, lichenification, and dryness) 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 intensity of pruritus. These are evaluated by having 
the subjects indicate on a 10.0-cm (0.0 – 10.0) visual analog scale (VAS)) the point corresponding 
to the average value for the last 3 days/nights. The combined maximum score of these two is 20.0. 




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• Proportion of subjects achieving at least a 4-point reduction from baseline in 
pruritus NRS at each available study visit 
5D-Pruritus Scale: 
The 5-D Pruritus Scale is a 1-page, 5-question, validated questionnaire used in clinical trials to 
assess 5 dimensions of background itch: degree, duration, direction, disability, and distribution. 
Each question corresponds to 1 of the 5 dimensions of itch; subjects will rate their symptoms over 
the preceding 2-week period as “present” or on a 1 to 5 scale, with 5 being the most affected.  
The scores of each of the five domains are achieved separately and then summed together to obtain 
a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25(most severe 
pruritus).  The score will be set to missing in case where at least one of the five domain results is 
missing.  Single-item domain scores (duration, degree and direction) are equal to the value in the 
response choice (range 1–5). The disability domain includes four items that assess the impact of 
itching on daily activities: sleep, leisure/social activities, housework/errands and work/school. The 
score for the disability domain is achieved by taking the highest score on any of the four items. 
For the distribution domain, the number of affected body parts is tallied (potential sum 0–16) and 
the sum is sorted into five scoring bins: sum of 0–2 = score of 1, sum of 3– 5 = score of 2, sum of 
6–10 = score of 3, sum of 11–13 = score of 4, and sum of 14–16 = score of 5.  
 
The 5D-Pruritus Scale will be assessed as  
• the change from baseline in 5-D Pruritus Scale at each available study visit 
Patient-Oriented Eczema Measure (POEM):  
The Patient-Oriented Eczema Measure (POEM) is a self-assessment of disease severity by the subject. 
The POEM has a maximum value of 28 based on the subject’s response to seven questions scored from 
0 to 4.  The score will be set to missing in case of at least one missing value. 
POEM will be assessed as  
• the change from baseline in POEM at each available study visit 
Dermatology Life Quality Index Questionnaire (DLQI):  
Dermatology Life Quality Index Questionnaire (DLQI) is a simple 10-question validated questionnaire 
that has been used in more than 40 different skin conditions. The DLQI is the most frequently used 






 
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The proportion of subjects withdrawing from worsening AD will be summarized at each available 
study visit.  
Listings of all AEs, all serious TEAEs, all TEAEs leading to study drug discontinuation, and all 
TEAEs leading to study discontinuation will be provided. 
13.2 Clinical Laboratory 
Descriptive statistics will be presented for data related to chemistry, hematology and quantitative 
urinalysis. Change from baseline values will be presented for each post-baseline assessment. 
Frequencies and percentages for each result will be provided for qualitative urinalysis data. 
Separate listings of all data for chemistry, hematology, urinalysis, and pregnancy tests will be 
provided. 
In addition, separate listings of data for chemistry, hematology, and urinalysis will be provided for 
each parameter where a subject had at least one abnormal result. 
13.3 Vital Signs 
Descriptive statistics will be presented for data related to vital signs (systolic blood pressure 
diastolic blood pressure, pulse rate and body temperature). Change from baseline values will be 
presented for each post-baseline assessment.  
A listing of all vital sign assessments will be provided. In addition, a listing will be provided for 
each parameter where a subject had at least one abnormal result 
13.4  Physical Examination 
Listings of abnormal physical examinations and all physical examination assessments will be 
provided 
13.5 Electrocardiogram (ECG) 
Descriptive statistics will be presented for data related to ECGs (heart rate, RR interval, PR 
interval, QRS duration, QT interval and QTcF interval). Change from baseline values will be 
presented for each post-baseline assessment.  
A listing of ECG assessments will be provided. In addition, a listing will be provided for each 
parameter where a subject had at least one abnormal result.  


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14 REFERENCES 
 
 
 


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15 APPENDICES 
Appendix 1 
Output Conventions 
TLF will be generated using SAS® and will be displayed on letter size paper with landscape 
orientation, 1 inch margins and 9 pt Courier New font. 
The header section will comprise the sponsor’s name, the protocol number, the delivery 
description, the data cut-off date (if applicable), the TLF number, the TLF title, the population, 
and the page number (Page X of Y). The footer section will include the TLF footnotes, the CRO’s 
name, the date and time of the execution of the program, and the name of the program. 
Mean, median, and quantiles will be displayed to one more decimal place than the original value; 
minimum and maximum will keep the same number of decimal places as the original value; 
standard deviation, standard error, and CI will be displayed to two more decimal places than the 
original value. If derived parameters are to be summarized, the number of decimals of the 
derived values is to be chosen on a case-by-case basis, but the rule above applies. 
For categorical summary tables, percentages will be reported to one decimal place. Percentages 
between 0 and 0.1 (both exclusive) will be displayed as “<0.1”. The denominator for each 
percentage will be the number of subjects within the population per treatment group unless 
otherwise specified. 
Listings will be ordered by ASN002 category (Starting ASN002/Continuing ASN002), treatment 
group (latest dose prior to the event/assessment for safety), subject number, date, and visit 
(where applicable). Imputed dates and imputed missing data will not be presented in the listings. 
Dates & Times Format 
Date and time (if available) will be presented in the format yyyy-mm-dd/hh:mm. 
 
 




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Appendix 2 
Algorithm for Imputation of Start/End Date of Adverse Events and 
Prior/Concomitant Medications 
Event Start Date Imputation 
• Imputation of event end date should be done before imputation of event start date.  
• Completely missing: Impute to the first study treatment date. 
• Missing day and month: Impute to January 1st, unless year is the same as year of first study 
treatment dose then impute to the first study treatment date. 
• Missing day: Impute to the 1st of the month, unless month and year are the same as month 
and year of first study treatment dose then impute to the first study treatment date. 
• If imputed event start date is after event end date (imputed or not), set the event start date 
to the imputed event end date. 
 
Event End Date Imputation 
• Completely missing (and not flagged as “ongoing”): Impute to the last contact date. 
• Missing day and month: Impute to December 31st, unless year is the same as last contact 
date then impute to the last contact date. 
• Missing day: Impute to the last day of the month, unless year and month are the same as 
year and month of last contact date then impute to the last contact date.