Clinical trial NCT03728504
Conditions: Chronic Hand Dermatitis
Keywords: eczema hand eczema hand dermatitis
Sponsor: Asana BioSciences
Start date: 2019-01-03; Completion date: 2020-04-29
Enrollment: 97 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Randomized double-blind/placebo study to evaluate the efficacy of ASN002 in subjects with severe chronic hand eczema.

Detailed description:
This is a placebo controlled study where subjects with severe chronic hand eczema will be randomized (1:1:1) to receive ASN002 at 40 mg, 80 mg, or placebo once daily for 16 weeks (Part A). Then, in Part B, subjects who were assigned to placebo in the first part of the study will receive the highest dose of ASN002 (80 mg) for the rest of the treatment period (up to Week 32). The subjects who were assigned ASN002 in the first part of the study will continue on the same assigned treatment dose during the second part of the study (Week 16 to Week 32). The total treatment period of 32 weeks will be followed by a 4 week follow-up period.This study will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling and three or four biopsies from subjects who consent.

Arms: arm 1: 40 mg ASN002 arm 2: 80 mg ASN002 arm 3: Matching placebo for ASN002 doses
Interventions: intervention 1: ASN002 intervention 2: Placebo Oral Tablet
Intervention descriptions: intervention 1: Daily dose of ASN002 for 32 weeks intervention 2: Daily dose of Placebo Oral Tablet for 16 weeks

Protocol documents:
Prot_000.pdf: 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 2 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................2 
PROTOCOL VERSION HISTORY ............................................................................................6 
STATEMENT OF COMPLIANCE ........................................................................................... 10 
SIGNATURE PAGE ................................................................................................................. 11 
PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE ......................................... 12 
LIST OF ABBREVIATIONS.................................................................................................... 13 
1 
PROTOCOL SUMMARY ......................................................................................... 15 
1.1 
Synopsis .................................................................................................................... 15 
1.2 
Study Diagram ........................................................................................................... 25 
1.3 
Schedule of Events..................................................................................................... 25 
2 
INTRODUCTION ..................................................................................................... 30 
2.1 
Background ............................................................................................................... 30 
 
Chronic Hand Eczema ....................................................................................... 30 
 
ASN002 .............................................................................................................. 30 
 
Study Rationale .................................................................................................. 31 
 
Known Potential Risks ....................................................................................... 32 
 
Known Potential Benefits ................................................................................... 32 
 
Assessment of Risks and Benefits ........................................................................ 32 
3 
OBJECTIVES AND ENDPOINTS ............................................................................ 33 
4 
STUDY DESIGN ...................................................................................................... 35 
4.1 
Overall Design ........................................................................................................... 35 
4.2 
Scientific Rationale for Study Design......................................................................... 36 
4.3 
End of Study Definition ............................................................................................. 36 
4.4 
Safety 
Monitoring 
criteria 
for 
Individual 
Subject 
Treatment 
Interruption/Discontinuation ...................................................................................... 36 
 
Interruption criteria ........................................................................................... 37 
 
Permanent study discontinuation........................................................................ 37 
5 
STUDY POPULATION ............................................................................................ 38 
5.1 
Inclusion Criteria ....................................................................................................... 38 
5.2 
Exclusion Criteria ...................................................................................................... 39 
5.3 
Screen Failures .......................................................................................................... 42 
6 
TREATMENT ........................................................................................................... 43 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 3 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
6.1 
Study Treatment Administered ................................................................................... 43 
 
Missed or Vomited Doses ................................................................................... 44 
 
Duration of Treatment........................................................................................ 44 
6.2 
Preparation/Handling/Storage/Accountability ............................................................ 44 
 
Preparation/Storage/Handling ........................................................................... 44 
 
Accountability .................................................................................................... 45 
6.3 
Randomization ........................................................................................................... 45 
 
Blinding ............................................................................................................. 46 
 
Study Treatment Compliance.............................................................................. 47 
 
Comparative Potencies of Topical Corticosteroids ............................................. 47 
 
Permitted Therapies ........................................................................................... 49 
 
Prohibited Therapies or Procedures................................................................... 50 
 
Concomitant Use of Drugs that may affect Gastric pH ....................................... 52 
 
Study Restrictions............................................................................................... 52 
7 
DISCONTINUATION AND LOST TO FOLLOW-UP .............................................. 52 
7.1 
Discontinuation .......................................................................................................... 53 
7.2 
Lost to Follow-Up ...................................................................................................... 53 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................... 54 
8.1 
Efficacy Assessments ................................................................................................. 54 
 
Modified Total Lesion Symptom Score ............................................................... 54 
 
Physician’s Global Assessment .......................................................................... 55 
 
Extent of Disease ............................................................................................... 56 
 
Hand Eczema Severity Index .............................................................................. 57 
 
Patient Global Assessment ................................................................................. 58 
8.2 
Skin Microbiome analysis .......................................................................................... 58 
8.3 
Patient Reported Outcomes ........................................................................................ 58 
 
Work Productivity and Activity Impairment Measure: Specific Health Problem . 58 
 
Dermatology Life Quality Index Questionnaire .................................................. 59 
 
Pain Visual Analog Scale ................................................................................... 59 
8.4 
Safety Assessments .................................................................................................... 59 
 
Vital Signs .......................................................................................................... 59 
 
Physical Examination......................................................................................... 60 
 
Brief Physical Examination ................................................................................ 60 
 
Clinical Laboratory Tests ................................................................................... 60 
 
Electrocardiogram ............................................................................................. 62 
8.5 
Pharmacokinetic and Pharmacodynamic Assessments ................................................ 62 
 
Pharmacokinetics Assessment in Blood .............................................................. 62 
 
Skin Biopsies ...................................................................................................... 62 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 4 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 
Tape stripping .................................................................................................... 63 
 
Pharmacodynamics Assessments in Blood .......................................................... 63 
 
PK/PD Relationship Assessments ....................................................................... 64 
8.6 
Other Assessments ..................................................................................................... 64 
 
Medical Photography ......................................................................................... 64 
 
Body Surface Area (for subjects with AD only) ................................................... 64 
 
Validated Investigator Global Assessment (for subjects with AD only) ............... 64 
8.7 
Adverse Events and Serious Adverse Events .............................................................. 65 
 
Definition of Adverse Event ................................................................................ 65 
 
Definition of Treatment-Emergent Adverse Event ............................................... 65 
 
Definition of Serious Adverse Event ................................................................... 65 
 
Classification of an Adverse Event ..................................................................... 66 
 
Time Period and Frequency for Event Assessment and Follow-Up ..................... 67 
 
Adverse Event Reporting .................................................................................... 68 
 
Serious Adverse Event Reporting ....................................................................... 68 
 
Pregnancy Reporting ......................................................................................... 69 
 
Overdose ............................................................................................................ 69 
9 
STATISTICAL CONSIDERATIONS ........................................................................ 69 
9.1 
Sample Size Determination ........................................................................................ 69 
9.2 
Populations for Analyses............................................................................................ 70 
9.3 
Statistical Analyses .................................................................................................... 70 
 
General Approach .............................................................................................. 70 
 
Efficacy Analyses ............................................................................................... 70 
 
Safety Analyses .................................................................................................. 71 
 
Pharmacokinetic Analyses ................................................................................. 72 
 
Pharmacodynamic Analyses ............................................................................... 72 
 
Other Analyses ................................................................................................... 72 
 
Planned Interim Analyses ................................................................................... 72 
10 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ..... 73 
10.1 
Local Regulations/Declaration of Helsinki ................................................................. 73 
11 
REFERENCES .......................................................................................................... 78 
APPENDIX A: Work Productivity and Activity Impairment Questionnaire (WPAI-SHP:CHE) 79 
APPENDIX B: Dermatology Life Quality Index ....................................................................... 81 
APPENDIX C: Diagnostic Criteria for Atopic Dermatitis ......................................................... 83 
APPENDIX D: vIGA-ADTM ..................................................................................................... 84 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 5 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
LIST OF TABLES 
 
Table 1. Schedule of Events ...................................................................................................... 26 
Table 2. Study Products............................................................................................................. 44 
Table 3. Comparative Potenciesa of Topical Corticosteroids8 .................................................... 48 
Table 4. Prohibited Therapies or Procedures.............................................................................. 51 
Table 5. Examples of H2 antagonists and Proton Pump Inhibitors ............................................. 52 
Table 6. Modified Total Lesion Symptom Score ....................................................................... 55 
Table 7. Physician’s Global Assessment .................................................................................... 56 
Table 8. Hand Eczema Severity Index ....................................................................................... 57 
Table 9. Patient Global Assessment2,10 ...................................................................................... 58 
Table 10. Clinical Laboratory Testing ....................................................................................... 61 
 
LIST OF FIGURES 
 
Figure 1: Study Diagram ........................................................................................................... 25 
Figure 2: Pain Visual Analog Scale ........................................................................................... 59 
 
 
 
 
 




Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 7 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
contraception requirements for 
male subjects 
 
 
 
 
 
To add an inclusion criterion for 
sperm donation 
 
 
 
 
 
To increase the frequency of 
pregnancy testing throughout 
study 
 
 
 
To add a visit at W18 for a total 
number of 13 visits 
 
 
 
 
 
 
 
To harmonize clinical laboratory 
testing and ECG assessments 
between Part A and Part B  
 
 
 
To add a footnote related to the 
emollient use 
days (not 4 weeks) after the last study 
product administration (i.e. full 
spermatogenesis cycle). The 4 weeks 
was also modified to 90 days for the 
female partners of male subjects using a 
hormonal contraceptive method.  
 
-Synopsis and Section 5.1: inclusion 
criterion #9 was added to prevent male 
subjects to donate sperm throughout the 
study starting at Day 1 and up to 90 days 
after the last study product 
administration. 
 
-Section 1.3 (Table 1): Urine pregnancy 
tests were added at the following visits: 
W2, W12, W18, W20 and W28 
following recommendation from the 
FDA and Health Canada. 
 
-Synopsis, Section 1.2 (Figure 1), 
Section 1.3 (Table 1), Section 4.1: A 
visit was added at Week 18 to assess 
vital signs and for AEs monitoring.  
 
 -Section 1.3 (Table 1, footer q); Section 
6.1: a mention was added to specify that 
dosing on Week 18 will occur at home. 
 
-Section 1.3 (Table 1): A ‘X’ was added 
to W20 for ECG assessment and to W20 
and W28 for clinical laboratory tests. 
Footnote corresponding to ECG was 
updated accordingly. 
 
-Section 1.3 (Table 1): footer was added 
to clarify that emollient use must start at 
least 1 week prior to Day 1. 
4.0 / 04 February 
2019 
To revise the wording for the 
PaGA secondary efficacy 
endpoint as no change from 
baseline can be evaluated for the 
PaGA measurement. 
 
 
 
 
 
 
-Synopsis and Section 3: wording was 
changed to “Actual PaGA measurements 
at Weeks 4, 8, 12, 16, 32” instead of 
“Change and percent change from 
baseline in hand Patient Global 
Assessment (PaGA) measurements at 
Weeks 4, 8, 12, 16, and 32”. 
 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 8 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
To correct a discrepancy in the 
footnote of the Schedule of 
Events for collection of biopsy 
samples. 
 
To revise the inclusion criterion 
related to body mass index 
(BMI) in order to increase 
subject eligibility by allowing a 
higher BMI. 
 
 To clarify that the number of 
tape strips required per sampling 
site is an approximate. 
 
 
To correct discrepancies in the 
statistical analyses section 
  
 
 
-Section 1.3, Table 1, Footnote l: 
Clarified that biopsies should be 
collected adjacent to the tape stripping 
site. 
 
-Synopsis and Section 5.1, inclusion 
criterion #6, BMI was revised to ≤ 38 
kg/m2. 
 
 
 
-Section 8.5.3 Tape stripping: It was 
clarified that “approximately” 20 tape 
strips are required per sampling site. 
 
 
-Synopsis and Section 9.3.2 Efficacy 
Analyses: clarified that the primary 
efficacy endpoint is “percent” change-
from-baseline in hand mTLSS at Week 
16. 
5.0 / 12 April 2019 
To allow inclusion of subjects 
with moderate CHE, as defined 
by a hand PGA 3 or 4. 
 
 
To specify that the 
randomization will be stratified 
for the PGA score and update the 
statistical analysis accordingly. 
 
 
 
 
To specify that inclusion of 
moderate CHE will be limited to 
30% of total enrollment. 
 
 
 
 
To add the moderate potency 
topical corticosteroids and 
systemic corticosteroids in the 
list of refractory treatment for 
CHE.   
 
 
 
-Added mention of moderate CHE 
throughout the protocol, where 
applicable. 
 
 
-Synopsis and Section 6.3: Added 
mention of stratification for the PGA 
score of ‘3’ (moderate) or ‘4’ (severe). 
-Synopsis and Section 9.3.2: Added 
mention of the PGA scores as a 
stratification factor. 
 
 
-Synopsis, Section 4.1 and Section 8.1.2: 
Added mention that Subjects with 
moderate CHE will be limited to 30% of 
total enrollment. 
 
 
 
-Cover page and Synopsis: Study title 
updated to remove mention specific to 
topical corticosteroid therapy.  
-Synopsis and Section 5.1: Inclusion 
criterion #3, updated to include moderate 
potency topical corticosteroids and 
systemic corticosteroids.  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 9 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 
 
 
 
 
 
To remove the sensitivity 
analyses for the primary efficacy 
endpoint. 
 
 
 
 
Minor discrepancy corrected. 
 
 
-Section 6.4 and 6.4.1: updated to 
include moderate potency topical 
corticosteroids and systemic 
corticosteroids.  
 
 
-Section 9.3.1: Removed the following 
sentence: Moreover, the analyses 
performed on observed case (i.e. without 
imputation of missing observations) will 
be done as sensitivity analyses. 
 
 
- Synopsis and Section 5.1: Added the 
abbreviation ‘e.g’ to inclusion criterion 
#7. 
 
6.0 / 01 October 
2019 
To update a sponsor contact.  
- Tittle Page: Updated the name of 
sponsor’s associate director – clinical 
operations, to reflect that Jaimini Shah 
occupies this position for now on. 
 
To remove the upper limit of age 
as requested by the FDA, as 
CHE occurs in patients >75 
years of age.  
- Synopsis, Section 4.1, and Section 5.1 
(Inclusion Criterion #1): Updated to 
include subjects aged 18 years or older 
in the study. 
 
 
To allow recruitment of up to 30 
additional subjects, because of 
the high dropout rate observed in 
the study. This will ensure the 
statistical power of the primary 
analysis is maintained by having 
at least 75 subjects completing 
the 16 weeks of treatment. 
- Synopsis and Section 4.1: Updated to 
allow inclusion of approximately 105 
subjects in the study. 
- Section 1.2 (study diagram): Updated 
the number of subjects to 35 for each 
group.  
- Synopsis and Section 9.1: Added the 
following sentence to the sample size 
considerations: Assuming between 
25-30% dropout rates, up to 35 patients 
per group will be included in this study. 
 
To correct the number of study 
centers participating in this 
study.  
- Synopsis and Section 4.1: Updated the 
number of study centers participating in 
this study from 15-20 to 20-25. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 10 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP), 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), 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 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 before the changes are implemented to the study. All changes to the 
consent form will be IRB approved. 




Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 12 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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, and applicable local regulations governing 
the conduct of clinical studies. 
 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 13 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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 
AUC 
area under concentration-time curve 
β-hCG 
β-human chorionic gonadotropin 
BMI 
body mass index 
BUN 
blood urea nitrogen 
CHE 
chronic hand eczema 
CK 
creatine kinase 
Cmax 
maximum observed concentration 
CRO 
contract research organization 
CRP 
C-reactive protein 
DLQI 
Dermatology Life Quality Index 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOS 
end of study 
EOT 
end of treatment 
ET 
early termination 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma-glutamyl-transferase 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCT 
hematocrit 
HCV 
hepatitis C virus 
HECSI 
hand eczema severity index 
Hgb 
hemoglobin 
HIV 
human immunodeficiency virus 
ICH 
International Council for Harmonisation 
IRB 
institutional review board 
LDH 
lactate dehydrogenase 
LMW 
low molecular weight  
Mapi 
Mapi Life Sciences 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA  
Medical Dictionary for Regulatory Activities 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 14 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
mITT 
modified intent-to-treat 
mTLSS 
modified Total Lesion Symptom Score  
MPV 
mean platelet volume 
NSAID 
nonsteroidal anti-inflammatory drug 
OTC 
over-the-counter (medication) 
PGA 
Physician’s Global Assessment 
PaGA 
Patient Global Assessment 
PK 
pharmacokinetic  
PLT 
platelets 
PP 
per-protocol  
PPD 
purified protein derivative  
PUVA 
psoralen-UV-A 
RBC 
red blood cell (count) 
REB 
research ethics board 
SAE 
serious adverse event 
SAF 
safety population 
SAP 
statistical analysis plan 
SD 
standard deviation 
t1/2 
half-life 
TB 
tuberculosis  
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
USA 
United States of America 
VAS 
visual analog scale 
vIGA 
validated Investigator Global Assessment 
VTE 
venous thromboembolic event 
WBC 
white blood cell (count) 
WOCBP 
women of childbearing potential 
WPAI-SHP 
work productivity and activity impairment specific health 
problem 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 15 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Name of Sponsor/Company: 
Asana BioSciences, LLC 
Name of Investigational 
Product: ASN002 
Name of Active Ingredient: 
ASN002 
Title of Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the 
Efficacy, Safety, Tolerability, and Pharmacokinetics of ASN002 in Subjects with Moderate to Severe 
Chronic Hand Eczema Refractory to Corticosteroid Therapy. 
Phase of Development:  
Phase 2 
Study Centers:  
Approximately 20-25 study centers located in the United States and Canada will participate in this study. 
Number of Subjects (planned):  
Approximately 105 subjects will be included in this study. 
Duration of Study:  
The maximum study duration per subject is up to 40 weeks (including up to 30 days for the screening 
period, followed by a 32-week treatment period, and up to 4 weeks for the follow-up period).  
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. 
Investigational Product, Dosage, and Mode of Administration:  
ASN002 40 mg, 80 mg or placebo will be orally administered once daily during the treatment period. 
ASN002 will be available in 20-mg strength tablets. 
Subjects will be randomized in a 1:1:1 ratio to one of the following treatment regimens: 
– 
Part A: ASN002 40 mg (16-week treatment); Part B: ASN002 40 mg (16-week treatment) 
– 
Part A: ASN002 80 mg (16-week treatment); Part B: ASN002 80 mg (16-week treatment) 
– 
Part A: Placebo (16-week treatment); Part B: ASN002 80 mg (16-week treatment) 
Subjects who were assigned to regimen starting with a placebo in Part A (first 16 weeks) of the study 
will receive the highest dose of ASN002 (80 mg) for the rest of the treatment period (up to 32 weeks of 
treatment). Subjects who were assigned to ASN002 in the first part of the study will continue on the 
assigned treatment dose during the second part of the study up 32 weeks of treatment. 
The blind will be maintained until the primary efficacy analyses are locked for Part A and all safety 
data for Part A has been cleaned and monitored. The CRO team and the sponsor will be unblinded after 
the database lock of Part A and safety data review, but the sites, investigators and subjects will remain 
blinded throughout the study.  Randomization will be stratified for the biopsy collection and for the 
PGA score of ‘3’ (moderate) or ‘4’ (severe).   


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 16 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
Objectives: 
Primary: 
• 
To evaluate the efficacy of ASN002 in subjects with moderate to severe chronic hand eczema 
(CHE), based on hand modified Total Lesion Symptom Score (mTLSS) 
Secondary: 
• 
To evaluate the efficacy of ASN002 in subjects with moderate to severe CHE, based on hand 
Physician’s Global Assessment (PGA) 
• 
To evaluate the safety and tolerability of ASN002 in subjects with moderate to severe CHE 
• 
To quantify the plasma concentrations of ASN002 in subjects with moderate to severe CHE 
Exploratory: 
• 
To evaluate pharmacodynamic (PD), biomarkers and skin microbiome analysis for evidence of 
drug activity in subjects with moderate to severe CHE  
• 
To assess population PK of ASN002 in subjects with moderate to severe CHE via a population 
PK analysis approach 
• 
To explore the relationships between PK exposure and clinical measurement (e.g., biomarker, 
efficacy and safety) as appropriate in subjects with moderate to severe CHE 
• 
To evaluate the effect of ASN002 on work productivity in subjects with moderate to severe CHE 
• 
To evaluate the efficacy of ASN002 on foot eczema in subjects with moderate to severe CHE 
Endpoints: 
Primary Endpoint: 
• 
Percent change from baseline in hand mTLSS at Week 16 
Secondary Endpoints: 
Secondary efficacy endpoints include: 
• 
Change from baseline in hand mTLSS at Weeks 4, 8, 12, 16, and 32 
• 
Percent change from baseline in hand mTLSS at Weeks 4, 8, 12, and 32 
• 
Proportion of subjects achieving at least a 2-grade reduction from baseline to clear (0), almost 
clear (1) or mild (2) in hand PGA at Weeks 4, 8, 12, 16, and 32 
• 
Proportion of subjects achieving a hand PGA of clear (0) or almost clear (1) at Weeks 4, 8, 12, 
16, and 32 
• 
Change and percent change from baseline in hand PGA at Weeks 4, 8, 12, 16, and 32  
• 
Change and percent change from baseline in Hand Eczema Severity Index (HECSI) at Weeks 4, 
8, 12, 16, and 32 
• 
Time to response relative to baseline (based on hand PGA) 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 17 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
• 
Actual PaGA measurements at Weeks 4, 8, 12, 16, 32  
• 
Change from baseline in hand Dermatology Life Quality Index (DLQI) at Weeks 2, 4, 8, 12, 16, 
and 32 
• 
Change and percent change from baseline in pain visual analog scale (VAS) at Weeks 4, 8, 12, 
16, and 32 
Secondary safety endpoints include: 
• 
Number of treatment-emergent adverse events (TEAEs)  
• 
Number of drug-related TEAEs  
• 
Proportion of subjects withdrawing for worsening of their CHE at Weeks 4, 8, 12, and 16 
• 
Changes in vital signs, electrocardiogram (ECG), and safety laboratory tests  
Secondary pharmacokinetic (PK) endpoint includes: 
• 
Measurement of plasma concentrations of ASN002 in all subjects receiving ASN002 treatment  
Exploratory Endpoints: 
Exploratory endpoints include: 
• 
Change from baseline in PD, biomarkers and skin microbiome analysis at Weeks 4 and 16 
• 
Characterization of population PK parameters via nonlinear mixed-effects modeling 
• 
Evaluate clinical safety, efficacy and biomarker measurements in relationship to PK exposure 
• 
Change and percent change from baseline in Extent of Disease affected with moderate to severe 
CHE at Weeks 4, 8, 12, 16, and 32 
• 
Change from baseline Work Productivity and Activity Impairment – Specific Health Problem 
(WPAI-SHP) questionnaire for hands at Weeks 4, 8, 12, 16, and 32 
• 
Change and percent change from baseline in foot mTLSS at Weeks 4, 8, 12, 16, and 32 
• 
Proportion of subjects achieving at least a 2-grade reduction from baseline to clear (0), almost 
clear (1) or mild (2) in foot PGA at Weeks 4, 8, 12, 16, and 32 
• 
Proportion of subjects achieving a foot PGA of clear (0) or almost clear (1) at Weeks 4, 8, 12, 
16 and 32 
• 
Change and percent change from baseline in foot PGA at Weeks 4, 8, 12, 16, and 32 
• 
Change and percent change from baseline in Extent of Disease affected with foot eczema at 
Weeks 4, 8, 12, 16, and 32 
Study Design: 
This study will be performed at approximately 20-25 study centers located in the United States and 
Canada. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 18 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
Approximately 105 subjects with moderate to severe CHE (as defined by a hand PGA 3 or 4 at Day 1) 
will be included in this randomized, double-blind, placebo-controlled, multicenter, Phase 2 study. 
Subjects will be men or women, 18 years of age or older, at the time of consent. Subjects with moderate 
CHE will be limited to 30% of total enrollment. 
Each subject should read and sign an informed consent form prior to any screening procedures being 
performed. Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria will be 
accepted into the study. After a screening period of no more than 30 days (from Day -30 to Day -1), 
eligible subjects will be randomized (1:1:1) on Day 1 to receive ASN002 at 40 mg or 80 mg, or placebo 
once daily for 16 weeks (Part A). Then, in Part B, subjects who were assigned to placebo in the first part 
of the study will receive the highest dose of ASN002 (i.e. 80 mg) for the rest of the treatment period (up 
to Week 32). The subjects who were assigned ASN002 in the first part of the study will continue on the 
same assigned treatment dose during the second part of the study (Week 16 to Week 32). The total 
treatment period of 32 weeks will be followed by a 4-week follow-up period. For scheduled study visits, 
subjects will come to the study centers on 13 occasions: screening; Day 1; Weeks 2, 4, 8, 12, 16, 18, 20, 
24, 28 and 32 (end of treatment visit); and Week 36 (follow-up visit)/early termination (ET).  
Efficacy will be assessed using mTLSS, PGA, HECSI, pain VAS and Extent of Disease. In addition, a 
6-grade PaGA scale will be used.  Quality of life will be evaluated using DLQI. Impact on work 
productivity and activity will be studied using the WPAI-SHP questionnaire.  
Safety will be assessed by collecting AEs, recording vital signs, performing physical examination and 
12-lead ECG, and evaluating clinical laboratory tests. 
Pre- and post-dose PK blood samples will be collected from all subjects on a sparse sampling schedule 
on Day 1 and Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 (or ET visit, if applicable).  
At selected study centers, in a subset of approximately 36 subjects who consent, PD blood samples will 
be collected pre-dose on Day 1 and Week 16 (or ET visit, if applicable and if it occurs prior to Week 
16). PD samples will be obtained from the same subjects who consent to biopsy collection. An additional 
PD blood sample will be collected at Week 4 in subjects who also consent to four skin biopsies. 
At selected study centers, in a subset of approximately 36 subjects who consent, three or four skin 
biopsies will be collected during this study. Two 2.5-mm punch biopsies (one from lesional skin and one 
from adjacent nonlesional skin) will be collected from the palmar aspect of the hand at Day 1, and one 
2.5-mm punch biopsy will be collected from the same lesional skin (outside the scar of the previous 
biopsy, at least 1 cm away from the previous scar) at Week 16 (or ET visit, if applicable and if it occurs 
prior to Week 16). In addition, one 2.5-mm punch biopsy will be collected from the same lesional skin 
(outside the scar of the previous biopsy, at least 1 cm away from the previous scar) at Week 4 in subjects 
who consent to four skin biopsies. 
For all subjects, on Day 1, and Weeks 4 and 16 (or ET visit, if applicable and if it occurs prior to 
Week 16), skin samples from the hands and feet (if feet involvement on Day 1) will be collected using 
tape stripping technique. On those same visits, skin microbiome samples will be collected from the worst 
hand eczema lesion and worst foot eczema lesion (if applicable). 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 19 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
Inclusion/Exclusion Criteria: 
Inclusion criteria:  
1. Male or female subject, 18 years of age or older, at the time of consent. 
2. Subject has a history of moderate to severe CHE for at least 6 months prior to baseline. (information 
obtained from medical chart or subject’s physician, or directly from the subject). 
3. Subject has hand eczema refractory to moderate potency, high potency or ultra-high potency topical 
corticosteroids (defined in Table 3) or systemic corticosteroids (including oral or injectable 
corticosteroids) used in the past year (information obtained from medical chart or subject’s 
physician, or directly from the subject). Refractory is defined by failure to achieve a status of clear, 
almost clear or mild CHE following at least a 2-week course of moderate potency, high potency or 
ultra-high potency topical corticosteroid or systemic corticosteroids (including oral or injectable 
corticosteroids). 
4. Subject has moderate to severe CHE at Day 1, as defined by a hand PGA 3 or 4. 
5. Subject has been using an emollient on their hands and feet (if foot eczema is present) (except those 
containing urea or salicylic acid) every day at the same frequency for at least 1 week prior to Day 1 
and agrees to continue using that same emollient, daily and at the same frequency, throughout the 
study. Note: On the day of scheduled visits, subjects cannot apply emollient before their scheduled 
visit time on their hands and feet. 
6. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
7. For female subject 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 (e.g. 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 (e.g. male condom with cervical 
cap, male condom with diaphragm, or male condom with 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: A female subject of nonchildbearing potential is as follows:  
a. Female subject who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy); 
b. Female subject 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).  
8. For male subject 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 #7, from Day 1 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 20 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
until at least 90 days after the last study product administration. If the female partner of a male 
subject use any of the hormonal contraceptive methods 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 by the male subject. 
9. Male subjects must not donate sperm from Day 1 until at least 90 days after the last study product 
administration. 
10. Female subject of childbearing potential has had a negative serum pregnancy test at screening and 
negative urine pregnancy test on 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:  
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during 
the study. 
2. Subject has known allergic contact dermatitis of the hands or hands and feet and is unable to avoid 
exposure to the causative allergen.  
3. Only for subjects with a history of atopic dermatitis (clinically confirmed diagnosis according to 
Hanifin and Rajka criteria (APPENDIX C)): the atopic dermatitis is covering > 15% of the BSA at 
baseline (Day 1) (excluding hands and feet). 
4. Only for subjects with a history of atopic dermatitis (clinically confirmed diagnosis according to 
Hanifin and Rajka criteria (APPENDIX C)): subject had a flare in his atopic dermatitis in the last 
4 weeks prior to the screening visit. 
5. Subject has active skin infections of the hands and/or feet. 
6. Subject has a history or has current active psoriasis. 
7. 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 
8. 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. 
9. 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.  
10. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Note: 
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. 
11. 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 21 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 has 12-lead ECG abnormalities considered by the investigator to be clinically significant or 
a QTcF ≥ 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be 
confirmed with one repeated assessment. For subjects with a QTcF ≥ 450 msec on initial ECG, the 
mean of the two QTcF values will determine eligibility. 
13. Subject has a history of congestive heart failure of class III or IV as per the New York Heart 
Association (NYHA) classification. 
14. Subject has a history of recurrent venous thromboembolic event (VTE) (≥ 2 episodes in the past). 
15. 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. 
16. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned during 
the study. 
17. Subject is known to have immune deficiency or is immunocompromised.  
18. 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. 
19. 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 < 0.9 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. 
20. Subject has uncontrolled hypertension within the last 1 month prior to screening or blood pressure 
at screening of systolic blood pressure > 160 mmHg or diastolic BP > 95 mmHg, confirmed by one 
repeat assessment. 
21. Subject has a known active tuberculosis (TB) or a positive 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 Bacillus 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). 
22. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
23. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 
24. Subject has a known history of diverticulitis. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 22 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
25. Subject has uncontrolled diabetes. 
26. 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. 
27. Subject has received any marketed or investigational biological agent within 12 weeks or 5 half-
lives (whichever is longer) prior to Day 1. 
28. Subject has used dupilumab within 12 weeks prior to Day 1.  
29. Subject is currently receiving a nonbiological investigational product or device or has received one 
within 4 weeks prior to Day 1. 
30. 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.  
31. Subject has used alitretinoin, isotretinoin, acitretin or other systemic retinoids within 4 weeks before 
Day 1, or has not completely recovered from its side effects. 
32. Subject has used systemic treatments (other than biologics) that could have an impact on CHE less 
than 4 weeks prior to Day 1 (e.g. methotrexate, cyclosporin), systemic steroids (including oral or 
injectable corticosteroids), or systemic immunosuppressants  
Note: Intranasal corticosteroids, eye or ear drops containing corticosteroids, and inhaled 
corticosteroids for stable medical conditions are allowed.  
33. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser within 
4 weeks prior to Day 1. 
34. Subject has had psoralen-UV-A (PUVA) treatment within 4 weeks prior to Day 1. 
35. Subject has had an excessive sun exposure, is planning a trip to a sunny climate, or has used tanning 
booths within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial sunlight 
exposure during the study. Use of sunscreen products and protective apparel are recommended when 
exposure cannot be avoided. 
36. Subject has used any topical treatments that could have an impact on CHE within 2 weeks prior to 
Day 1, including, but not limited to, topical corticosteroids, topical retinoids, crisaborole, calcineurin 
inhibitors, tars, bleach, bleach baths, antimicrobials, medical devices.  
37. Subject has used systemic antibiotics within 2 weeks prior to Day 1. 
38. Subject has used topical antibiotics within 2 weeks prior to Day 1. 
39. Subject has used topical products containing urea or salicylic acid within 1 week prior to Day 1. 
40. Subject has used ASN002 prior to Day 1. 
41. Subject had prior treatment with a systemic SYK or JAK inhibitor for which the subject received no 
clinical benefit in the opinion of the investigator, or the subject relapsed whilst on therapy, or was 
withdrawn for safety reasons. 
42. Subject has a known hypersensitivity to ASN002 or its excipients. 
43. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to 
Day 1. 
44. 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 23 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
45. Subject is institutionalized because of legal or regulatory order. 
46. Only for subjects consenting to biopsies: 
a. Subject has a history of an allergic reaction or significant sensitivity to lidocaine or other 
local anesthetics or their components; 
b. Subject has a history of hypertrophic scarring or keloid formation in scars or suture sites; 
c. Subject is taking anticoagulant medication, such as heparin, low molecular weight 
(LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin which will be allowed), 
within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. Note: Nonsteroidal 
anti-inflammatory drugs (NSAIDs) will not be considered antiplatelets and will be allowed. 
Statistical methods:  
Continuous variables will be summarized in tables and will include the number of subjects, mean, 
standard deviation (SD), percent of coefficient of variance (CV%), median, minimum, and maximum. 
Categorical variables will be presented in tables as frequencies and percentages. A statistical analysis 
plan (SAP) will provide additional details on the approach to the analysis and data displays. 
Efficacy Analyses: 
The primary efficacy endpoint will be analyzed using a repeated measures analysis of covariance on 
percent change-from-baseline variable to compare the time profile between treatments where the visit 
will be the time factor; and the stratification factor PGA score, treatment group, and interaction term for 
treatment-by-visit will be the fixed effects and the baseline value will be the covariate. An unstructured 
variance-covariance matrix will be used.  
For categorical efficacy endpoints involving proportions of PGA (e.g. the proportion of subjects 
achieving at least a 2-grade reduction from baseline to clear (0) or almost clear (1) in PGA at Week 16), 
a Cochran Mantel Hansel test (CMH) controlling for PGA score at baseline will be performed. 
Safety Analyses: 
The safety analysis will include reported AEs and other safety information (i.e., clinical laboratory 
evaluations, vital signs, physical examination, and 12-lead ECG results). A summary of safety results 
will be presented for each treatment group. 
PK Analyses: 
ASN002 concentration data will be summarized based on nominal timepoints using descriptive statistics, 
such as mean, SD, CV%, median, minimum and maximum.  
Population PK analysis will be performed using nonlinear mixed-effects modeling approach with first-
order conditional methods. This analysis may be combined with PK concentrations from other clinical 
trials in healthy and AD subjects as appropriate.  
PD Analyses: 
Biomarker levels will be compared to placebo adjusted change from baseline over time for each 
treatment group, and the parameters will be summarized by treatment group and overall using descriptive 
statistics.  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 24 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
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 
PK/PD Analyses: 
PK-efficacy, PK-safety and PK-biomarkers relationships will be explored using linear regression, loess 
plots, Hills functions, or logistic regression, as appropriate. 
Primary statistical analysis: 
Unblinded primary efficacy analyses will be performed after Week 16 is completed for all subjects. The 
CRO team and the sponsor will be unblinded after the database lock of Part A for the efficacy 
assessments, and a cleaning and monitoring of all safety data collected in Part A. The sites, investigators 
and subjects will remain blinded throughout the study.  
Sample Size Consideration: 
Assuming a common standard deviation of 39% for the % change-from-baseline mTLSS, a difference 
of 25% and 35% between the 40 mg dose vs. placebo and the 80 mg dose vs. placebo, respectively, alpha 
of 5% (two-sided), 25 patients per group would insure an 80% power to obtain a statistically significant 
treatment effect (using the general F test in an analysis of variance). Assuming between 25-30% dropout 
rates, up to 35 patients per group will be included in this study.  
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 25 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
1.2 Study Diagram 
Figure 1: Study Diagram 
 
 
1.3 Schedule of Events 
The screening evaluation will only be performed after the subject has agreed to participate and has 
signed and dated the informed consent form. No treatment or trial-related procedures will be 
initiated before the informed consent is signed. The Day 1 visit must be performed, at the latest, 
30 days after the screening visit. The screening evaluation will be performed according to the 
inclusion and exclusion criteria. If the subject fulfills all inclusion criteria and no exclusion criteria, 
he or she may be included in the study.  
Table 1 provides a description of the procedures to be performed at each visit. 
Unless specified otherwise, the study assessments scheduled during the study visits will be 
performed before the study product administration. If assessments are scheduled for the same 
nominal time, then the assessments should occur in the following order: 
• Patient reported outcomes and PaGA 
• Vital signs  
• 12-lead ECG 
• Blood draw for PK evaluations (time window vs drug administration detailed in footer of  
Table 1) and/or safety blood draw 
Note: The timing of the assessments should allow the blood draw to occur within the allowed 
window of the nominal time. 










Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 30 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
2 INTRODUCTION 
2.1 Background 
 Chronic Hand Eczema 
Chronic hand eczema (CHE) causes itching, pain, discomfort as well as embarrassment caused by 
the inconvenient location of the disease.1 Severe CHE leads to disfiguring changes in hand 
appearance caused by the classic features of eczema, such as erythema, oedema, 
vesiculation/blistering, hyperkeratosis, fissures, pruritus and pain leading to considerable 
occupational, functional, social and psychological disabilities.2 Yearly hand eczema (HE) is 
thought to present itself in 7%~12% in the general population in Northern Europe and could 
possibly be higher in the USA.2 Among the sufferers of HE, 5-7 % are thought to develop severe 
CHE.3 This condition is known to interfere greatly with daily activities and work assiduity of over 
81% of the affected population. Severe CHE can seriously disturb a patient’s daily life, leading to 
prolongated sick leave or even forcing a change in their career choice.4 The most common type of 
HE comprise of irritant contact dermatitis, atopic hand eczema and allergic contact dermatitis.4 
Exposure to irritants or allergens such as nickel, cobalt, fragrance-mix, colophony and unspecified 
chemicals, water and detergents or dust and dry dirt could trigger the disease. Endogenous factors 
such as atopic dermatitis (AD) could also be a risk factor.2,4,5  
Mild cases of CHE can be controlled with diligent use of emollients and topical corticosteroids 
combined with the avoidance of potential irritants, but severe CHE is debilitating as this prescribed 
regimen is usually inefficient.2 A Swedish study disclosed that treatment for HE with topical 
steroids was reported by 51% of patients while emollients were used by 85%. Of the 1385 patients 
who answered the questionnaire, 81% experienced some kind of disturbance of their daily life 
considered to be caused by the HE. 69% of the patients had consulted a doctor and 21% had been 
on sick-leave at least once because of their HE.4  
Severe CHE is characterized as hand eczema that shows a prolonged and relapsing course or is 
unresponsive to standard treatment using emollients and topical corticosteroids.6 Among the 
sufferers of severe CHE, 2%~4% are unresponsive to standard treatment.5 There are no approved 
systemic treatments for CHE in the US.  Alitretinoin, a systemic retinoid, is approved in Canada 
and several countries for CHE but only half of treated patients will achieve a clear or almost clear 
status after 16 weeks of therapy.2 Other systemic therapies such as cyclosporine are sometimes 
used off-label in severe, chronic, and refractory cases.2,6 
There is a definite need for randomized controlled clinical trials of existing and new treatment 
options based on clearly diagnosed subtypes of hand eczema and their various severities.7 
 ASN002  
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 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 31 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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 provide strong rationale 
for its evaluation in the treatment of inflammatory disorders, such as CHE. In a Phase 1b study 
(ASN002AD-101), plasma concentrations of ASN002 were measured in subjects with AD 
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 in that Phase 1b study. 
The most common adverse event (AE) observed was transient, mild headache, mostly restricted to 
Day 1 likely due to fasting. There were no clinically significant laboratory changes including 
hematological parameters observed in this study. ASN002 showed robust clinical efficacy with 
nearly all patients obtaining a 50% improvement in disease severity (EASI50) at 40 mg and 80 mg 
once daily and substantial decreases in patient-reported itch measured by Numeric Rating Scale 
(NRS) after 4 weeks of treatment.  
 Study Rationale 
In the previous clinical trial (ASN002AD-101), ASN002 has showed significant benefit for the 
treatment of AD, especially at 40 and 80 mg once-daily dosing regimens. It is hypothesized that 
the efficacy of ASN002 in AD will also be observed in CHE. This trial is therefore to investigate 
the benefit and risk of ASN002 in subjects with moderate to severe CHE for a 16-week treatment 
duration, followed by a 16-week treatment extension. 
Current therapies for moderate to severe chronic hand eczema provide relief of symptoms for some 
but not all patients. There is definitely a need for new treatments in moderate to severe CHE in 
order to increase the existing options available to clinicians. 
The primary objective of this study is to assess the efficacy of ASN002 in subjects with moderate 
to severe CHE. Safety and tolerability of ASN002 will also be evaluated as secondary endpoint as 
well as its PK profile. The doses to be administered in this study are 40 and 80 mg, which were 
found to be well tolerated and safe in a previous Phase 1b study. AEs observed in the Phase 1b 
study were of mild or moderate intensity following 80 mg dose.  Once daily administration was 
chosen based on the data from the clinical studies in oncology subjects and healthy volunteers. PK 
analysis indicate sufficient systemic exposure for ASN002 efficacy and a half-life (t1/2) of ~10 
hours is adequate for maintaining target trough concentrations. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 32 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
2.2 Risk/Benefit Assessment 
 Known Potential Risks 
The data from both nonclinical and clinical studies with ASN002 suggest that it is safe and well-
tolerated at the doses to be administered in the present study.  
In cancer subjects, ASN002 has been well tolerated. The most common reported AEs were anemia, 
fatigue, chills, dizziness and diarrhea, as expected in heavily pretreated and refractory cancer 
patients. 
The safety of ASN002 have also been studied in a safety, tolerability, PK and food effect study in 
healthy subjects at doses up to 100 mg following a single oral administration. The most common 
AE in this study was headache. One serious adverse event (SAE), premature ventricular 
contractions, which were asymptomatic and mild, was experienced by one subject dosed with 50 
mg ASN002 once. These resolved over 5 days without sequelae. This event was considered 
possibly related to study medication and unexpected. 
The safety of ASN002 was also assessed in a previous Phase 1b study in AD patients. Adverse 
events (AEs) observed in the Phase I study were mild or moderate at doses up to 80 mg.  There 
were no drug-related SAEs reported in this study. One SAE was reported (anxiety attack), which 
was not related to the study drug. In addition, one event led to treatment discontinuation for one 
subject (hypertension) in the 80-mg cohort. The corresponding patient was also on Ritalin and was 
observed with fluctuating blood pressure measurement results even after clearance of the study 
drug suggesting Stage 1 hypertension levels. It is also important to note that the patient also had 
borderline high level of blood pressure at baseline. Considering the above, this study suggests that 
ASN002 is safe and well-tolerated at doses up to 80 mg.  
Further information related to previous clinical studies is available in the Investigator Brochure. 
 Known Potential Benefits 
It is anticipated that subjects will see an improvement in their moderate to severe CHE condition 
as a result of participating in this study, if they are randomized to active investigational product. 
Participation in this study may help generate future benefit for larger groups of patients with CHE. 
 Assessment of Risks and Benefits 
All quality, pharmacology and toxicology data, and satisfactory safety and tolerability data 
demonstrated in nonclinical studies are considered sufficient to expect a positive benefit/risk ratio 
for the treatment of CHE 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. 






Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 35 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
4 STUDY DESIGN  
4.1 Overall Design  
This study will be performed at approximately 20-25 study centers located in the United States 
and Canada. 
Approximately 105 subjects with moderate to severe CHE (as defined by a hand PGA 3 or 4 at 
Day 1) will be included in this randomized, double-blind, placebo-controlled, multicenter, Phase 
2 study. Subjects will be men or women, 18 years of age or older, at the time of consent. Subjects 
with moderate CHE will be limited to 30% of total enrollment. 
Each subject should read and sign an informed consent form prior to any screening procedures 
being performed. Subjects who fulfill all of the inclusion criteria and none of the exclusion criteria 
will be accepted into the study. After a screening period of no more than 30 days (from Day -30 
to Day -1), eligible subjects will be randomized (1:1:1) on Day 1 to receive ASN002 at 40 mg or 
80 mg, or placebo once daily for 16 weeks (Part A). Then, in Part B, subjects who were assigned 
to placebo in the first part of the study will receive the highest dose of ASN002 (i.e. 80 mg) for 
the rest of the treatment period (up to Week 32). The subjects who were assigned ASN002 in the 
first part of the study will continue on the same assigned treatment dose during the second part of 
the study (Week 16 to Week 32). The total treatment period of 32 weeks will be followed by a 
4-week follow-up period. For scheduled study visits, subjects will come to the study centers on 13 
occasions: screening; Day 1; Weeks 2, 4, 8, 12, 16, 18, 20, 24, 28 and 32; and Week 36 (follow-up 
visit)/early termination (ET).  
Efficacy will be assessed using mTLSS, PGA, HECSI, pain VAS and Extent of Disease. In 
addition, a 6-grade PaGA scale will be used.  Quality of life will be evaluated using DLQI. Impact 
on work productivity and activity will be studied using the WPAI-SHP questionnaire.  
Safety will be assessed by collecting AEs, recording vital signs, performing physical examination 
and 12-lead ECG, and evaluating clinical laboratory tests. 
Pre- and post-dose PK blood samples will be collected from all subjects on a sparse sampling 
schedule on Day 1 and Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32 (or ET visit, if applicable).  
At selected study centers, in a subset of approximately 36 subjects who consent, PD blood samples 
will be collected pre-dose on Day 1 and Week 16 (or ET visit, if applicable and if it occurs prior 
to Week 16). PD samples will be obtained from the same subjects who consent to biopsy collection. 
An additional PD blood samples will be collected at Week 4 in subjects who also consent to four 
skin biopsies. 
At selected study centers, in a subset of approximately 36 subjects who consent, three or four skin 
biopsies will be collected during this study. Two 2.5-mm punch biopsies (one from lesional skin 
and one from adjacent nonlesional skin) will be collected from the palmar aspect of the hand at 
Day 1, and one 2.5-mm punch biopsy will be collected from the same lesional skin (outside the 
scar of the previous biopsy, at least 1 cm away from the previous scar) at Week 16 (or ET visit, if 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 36 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
applicable and if it occurs prior to Week 16). In addition, one 2.5-mm punch biopsy will be 
collected from the same lesional skin (outside the scar of the previous biopsy, at least 1 cm away 
from the previous scar) at Week 4 in subjects who consent to four skin biopsies. 
For all subjects, on Day 1, and Weeks 4 and 16 (or ET visit, if applicable and if it occurs prior to 
Week 16), skin samples from of the hand and foot (if subject has presence of foot eczema on Day 
1) will be collected using tape stripping technique. During the same visits, skin microbiome 
samples will be collected from the worst eczema lesion of the hand (palmar aspect, when possible) 
and worst eczema lesion of the foot (plantar aspect, when possible) (if subject has presence of foot 
eczema on Day 1). The microbiome sampling must be collected prior to tape stripping and 
biopsies.  
Preferably, all skin sampling (microbiome samples, tape strips and biopsies) should be collected 
from the same lesion.   
At selected study centers, in a subset of approximately 36 subjects who consent, medical 
photographs of both aspects (palmar and dorsal) of both hands will be taken.   
4.2 Scientific Rationale for Study Design  
The proposed design is considered appropriate for assessing the efficacy of ASN002 study 
products compared to a placebo in subjects with moderate to severe chronic hand eczema, and to 
evaluate the safety and tolerability of ASN002 study product in subjects with moderate to severe 
chronic hand eczema. 
 
The study will be randomized to ensure random allocation of subjects to treatment arms to reduce 
bias. Because efficacy assessments of moderate to severe chronic hand eczema have a high degree 
of subjectivity, the study will be double-blinded. The highest degree of subjects and assessor 
blinding should be sought to achieve credible inference. It is also important to have a placebo 
control in a Phase 2 study to control for confounding factors, such as potential investigator bias, 
and to ensure that the statistical procedures can be appropriately applied.  
4.3 End of Study Definition 
A subject is considered to have completed the study if he or she has completed all phases of the 
study, including the last visit or the last scheduled procedure shown in the Schedule of Events, 
Table 1. 
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 temporarily or permanently discontinued based on the investigator’s judgment and preferably 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 37 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
following a discussion with the medical monitor in accordance with the guidelines described in 
this section.  
Treatment may be resumed upon recovery to baseline or mild levels after the condition leading to 
suspension of dosing resolves, at the discretion of the principal investigator in consultation with 
the medical monitor.  A decision to temporarily discontinue study drug and/or to reinstitute study 
treatment should be discussed with the medical monitor.  The investigator may suspend study 
treatment at any time, even without consultation with the medical monitor if the urgency of the 
situation requires immediate action and if this is determined to be in the subject’s best 
interest.  However, the medical monitor should be contacted as soon as possible in any case of 
study drug discontinuation/interruption.  Resumption of study treatment after temporary 
discontinuation should always be discussed with the medical monitor. 
Any retreatment should only be considered upon written agreement between the investigator and 
the sponsor. This information pertaining to interruption or discontinuation of study medication and 
the reasons for it must be recorded in the case report form. 
No dose reductions or modifications are permitted. 
 Interruption criteria 
A subject who meets either of the below criteria will have the study drug interrupted until 
laboratory retesting is performed and/or event resolution.  
 
• neutrophils > 0.5 x 103 /μL but < 1 x 103 /μL; 
• platelet count > 50 x 103 /μL but < 100 x 103 /μL; 
• lymphocytes > 0.2 x 103 /μL but < 0.5 x 103 /μL; 
• CPK >10 x ULN; 
• an infection requiring IV treatment with antiviral, antibiotic, antiprotozoal, antiparasite or 
requiring oral medications of those longer than 2 weeks; 
• AST/ALT > 5 x ULN*. 
 
*Decision to restart the medication following any laboratory abnormality described above will 
be made in consultation with the study sponsor and medical monitor. 
 Permanent study discontinuation 
Adverse events or laboratory abnormalities who meet either of the below criteria will result in 
permanent study discontinuation of the subject. Treatment with the study product will be 
immediately stopped and the subject withdrawn from this study. 
• serious opportunistic infection such as tuberculosis;  
• hypertension that cannot be controlled with additional antihypertensive medication(s); 
• neutrophils ≤ 0.5 x 103 /μL; 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 38 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
• lymphocytes ≤ 0.2 x 103 /μL; 
• platelets ≤ 50 x 103 /μL; 
• diagnosis of malignancy; 
• venous thrombo-embolic event or major cardiovascular event. 
5 STUDY POPULATION  
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, a subject must meet all of the following criteria 
at the screening and Day 1 visits, unless specified otherwise:  
1. Male or female subject, 18 years of age or older, at the time of consent. 
2. Subject has a history of moderate to severe CHE for at least 6 months prior to baseline. 
(information obtained from medical chart or subject’s physician, or directly from the subject). 
3. Subject has hand eczema refractory to moderate potency, high potency or ultra-high potency 
topical corticosteroids (defined in Table 3) or systemic corticosteroids (including oral or 
injectable corticosteroids) used in the past year (information obtained from medical chart or 
subject’s physician, or directly from the subject). Refractory is defined by failure to achieve a 
status of clear, almost clear or mild CHE following at least a 2-week course of moderate 
potency, high potency or ultra-high potency topical corticosteroid or systemic corticosteroids 
(including oral or injectable corticosteroids). 
4. Subject has moderate to severe CHE at Day 1, as defined by a hand PGA 3 or 4. 
5. Subject has been using an emollient on their hands and feet (if foot eczema is present) (except 
those containing urea or salicylic acid) every day at the same frequency for at least 1 week 
prior to Day 1 and agrees to continue using that same emollient, daily and at the same 
frequency, throughout the study. Note: On the day of scheduled visits, subjects cannot apply 
emollient before their scheduled visit time on their hands and feet. 
6. Subject has a body mass index (BMI) ≤ 38 kg/m2. 
7. For female subject 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 (e.g. 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 
(e.g. male condom with cervical cap, male condom with diaphragm, or male condom with 
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.  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 39 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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: A female subject of nonchildbearing potential is as follows:  
a. Female subject who has had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or bilateral salpingectomy); 
b. Female subject 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).  
8. For male subject 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 #7, 
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 contraceptive methods 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 by the male subject. 
9. Male subjects must not donate sperm from Day 1 until at least 90 days after the last study 
product administration. 
10. Female subject of childbearing potential has had a negative serum pregnancy test at screening 
and negative urine pregnancy test on 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. 
5.2 Exclusion Criteria 
A subject who meets any of the following criteria at the screening and Day 1 visits, unless specified 
otherwise, will be excluded from participation in this study: 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant 
during the study. 
2. Subject has known allergic contact dermatitis of the hands or hands and feet and is unable to 
avoid exposure to the causative allergen.  
3. Only for subjects with a history of atopic dermatitis (clinically confirmed diagnosis according 
to Hanifin and Rajka criteria (APPENDIX C)): the atopic dermatitis is covering > 15% of the 
BSA at baseline (Day 1) (excluding hands and feet) 
4. Only for subjects with a history of atopic dermatitis (clinically confirmed diagnosis according 
to Hanifin and Rajka criteria (APPENDIX C)): subject had a flare in his atopic dermatitis in 
the last 4 weeks prior to the screening visit. 
5. Subject has active skin infections of the hands and/or feet. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 40 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
6. Subject has a history or has current active psoriasis. 
7. 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 
8. 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. 
9. 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.  
10. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. 
Note: 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. 
11. 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. 
12. Subject has 12-lead ECG abnormalities considered by the investigator to be clinically 
significant or a QTcF ≥ 450 milliseconds, regardless of clinical significance, at screening. 
Abnormal ECG may be confirmed with one repeated assessment. For subjects with a QTcF ≥ 
450 msec on initial ECG, the mean of the two QTcF values will determine eligibility. 
13. Subject has a history of congestive heart failure of class III or IV as per the New York Heart 
Association (NYHA) classification. 
14. Subject has a history of recurrent venous thromboembolic event (VTE) (≥ 2 episodes in the 
past). 
15. 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. 
16. Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned 
during the study. 
17. Subject is known to have immune deficiency or is immunocompromised.  
18. 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. 
19. 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 < 0.9 x 103 /μL; 
f. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 x the upper 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 41 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
limit of normal (ULN). 
g. Total bilirubin > 1.2 x ULN (except for elevated indirect bilirubin secondary to 
Gilbert’s syndrome); 
h. Creatinine > ULN. 
20. Subject has uncontrolled hypertension within the last 1 month prior to screening or blood 
pressure at screening of systolic blood pressure > 160 mmHg or diastolic BP > 95 mmHg, 
confirmed by one repeat assessment. 
21. Subject has a known active tuberculosis (TB) or a positive 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 Bacillus 
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). 
22. Subject has difficulty swallowing medications, or known history of malabsorption syndrome. 
23. Subject has a history of recurrent gastroesophageal reflux disease (GERD) requiring the use of 
proton pump inhibitors within the last month. 
24. Subject has a known history of diverticulitis. 
25. Subject has uncontrolled diabetes. 
26. 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. 
27. Subject has received any marketed or investigational biological agent within 12 weeks or 
5 half-lives (whichever is longer) prior to Day 1. 
28. Subject has used dupilumab within 12 weeks prior to Day 1.  
29. Subject is currently receiving a nonbiological investigational product or device or has received 
one within 4 weeks prior to Day 1. 
30. 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.  
31. Subject has used alitretinoin, isotretinoin, acitretin or other systemic retinoids within 4 weeks 
before Day 1, or has not completely recovered from its side effects. 
32. Subject has used systemic treatments (other than biologics) that could have an impact on CHE 
less than 4 weeks prior to Day 1 (e.g. methotrexate, cyclosporin), systemic steroids (including 
oral or injectable corticosteroids), or systemic immunosuppressants  
Note: Intranasal corticosteroids, eye or ear drops containing corticosteroids, and inhaled 
corticosteroids for stable medical conditions are allowed.  
33. Subject has received any UV-B phototherapy (including tanning beds) or excimer laser within 
4 weeks prior to Day 1. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 42 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
34. Subject has had psoralen-UV-A (PUVA) treatment within 4 weeks prior to Day 1. 
35. Subject has had an excessive sun exposure, is planning a trip to a sunny climate, or has used 
tanning booths within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial 
sunlight exposure during the study. Use of sunscreen products and protective apparel are 
recommended when exposure cannot be avoided. 
36. Subject has used any topical treatments that could have an impact on CHE within 2 weeks 
prior to Day 1, including, but not limited to, topical corticosteroids, topical retinoids, 
crisaborole, calcineurin inhibitors, tars, bleach, bleach baths, antimicrobials, medical devices.  
37. Subject has used systemic antibiotics within 2 weeks prior to Day 1. 
38. Subject has used topical antibiotics within 2 weeks prior to Day 1. 
39. Subject has used topical products containing urea or salicylic acid within 1 week prior to Day 1. 
40. Subject has used ASN002 prior to Day 1. 
41. Subject had prior treatment with a systemic SYK or JAK inhibitor for which the subject 
received no clinical benefit in the opinion of the investigator, or the subject relapsed whilst on 
therapy, or was withdrawn for safety reasons. 
42. Subject has a known hypersensitivity to ASN002 or its excipients. 
43. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior 
to Day 1. 
44. 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. 
45. Subject is institutionalized because of legal or regulatory order. 
46. Only for subjects consenting to biopsies: 
a. Subject has a history of an allergic reaction or significant sensitivity to lidocaine or 
other local anesthetics or their components; 
b. Subject has a history of hypertrophic scarring or keloid formation in scars or suture 
sites; 
c. Subject is taking anticoagulant medication, such as heparin, low molecular weight 
(LMW)-heparin, warfarin, antiplatelets (except low-dose aspirin which will be 
allowed), within 2 weeks prior to Day 1, or has a contraindication to skin biopsies. 
Note: Nonsteroidal anti-inflammatory drugs (NSAIDs) will not be considered 
antiplatelets and will be allowed. 
5.3 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 treatment. 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 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 43 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
to queries from regulatory authorities. Minimal information includes demography, screen failure 
details, eligibility criteria, and any SAEs. 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened once, if deemed acceptable by the investigator. Rescreened subjects should be assigned 
a different subject number than the initial screening. All procedures planned at the screening visit, 
including signature of a new consent form, will be performed. 
Subjects who do not qualify to participate in the study due to a vital sign or screening laboratory 
value abnormality can repeat the test once within the original screening time window without 
resulting in screen failure, if the investigator believes there is a reasonable possibility that the 
subject would be eligible if re-tested. 
6 TREATMENT 
6.1 Study Treatment Administered 
This study involves two different doses of ASN002 (40 mg and 80 mg) both orally administered 
once daily compared to a placebo in Part A (first 16 weeks of treatment). Then, only active 
products (ASN002 40 mg and 80 mg) will be administered in Part B. ASN002 will be available in 
20-mg strength tablets. All study products will be provided by the sponsor. All study products will 
be self-administered orally, at home or at the clinic on clinic visit days. 
Study products administration will occur daily for 32 weeks at approximately every 24 hours, on 
an empty stomach (2 hours before and 2 hours after a meal) with approximately 240 mL of water. 
On visit days, the study products will be administered at the study center, except at Week 18. The 
date and time of the drug administration and fasting conditions will be collected by the study site 
on the visit days. When dosing at home, the subject will be instructed to take the study product at 
approximately the same time of the day and compliance will be self-reported during each study 
visits. 
Further details regarding the study products for Part A can be found in Table 2. 




Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 45 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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. At the conclusion of the study, all used and 
unused investigational products and all medication containers will be returned to the sponsor unless 
the sponsor has approved other arrangements.  Any study product accidentally or deliberately 
destroyed, or returned to the sponsor or designee will be accounted for. Any discrepancies between 
amounts dispensed and returned will be explained. 
 
All study product accountability forms and treatment logs must be retained in the investigator’s 
study files. Product inventory and accountability records will be maintained as per ICH GCP. 
These records must be available for inspection at any time by the sponsor, its designees, or by 
regulatory agencies. 
Further guidance and information for final disposition of study products are provided in the study 
manual.  
6.3 Randomization 
At the investigational site, each screened subject will be assigned a subject identifier number 
during screening that will be used on all subject documentation. The subject identifier number will 
contain the site number and the subject number and will be assigned in numerical order at the 
screening visit based on chronological order of screening dates (e.g., 02-010 for the 10th subject 
screened at the Site #02). 
Subjects will be randomized in a 1:1:1 ratio to one of the following treatment regimens: 
– 
Part A: ASN002 40 mg (16-week treatment); Part B: ASN002 40 mg (16-week 
treatment) 
– 
Part A: ASN002 80 mg (16-week treatment); Part B: ASN002 80 mg (16-week 
treatment) 
– 
Part A: Placebo (16-week treatment); Part B: ASN002 80 mg (16-week treatment) 
Subjects assigned to regimen starting with a placebo in Part A (first 16 weeks) of the study will 
receive the highest dose of ASN002 (i.e. 80 mg) for the rest of the treatment period (up to Week 
32). Subjects who were assigned to ASN002 in the first part of the study will continue on the 
assigned treatment dose during the second part of the study up 32 weeks of treatment. 
Randomization will occur prior to first dosing, at Day 1 visit. The randomization list will be 
generated using a validated software. Randomization will be stratified for the biopsy collection 
and for the PGA score of ‘3’ (moderate) or ‘4’ (severe) per treatment group. The master 
randomization list will be kept secured until the study blind is broken. This list will be uploaded 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 46 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
into an Interactive Web Response System (IWRS). The investigator or designee will be able to 
acquire a randomization number for eligible subjects by connecting to the IWRS. 
Further guidance and information can be obtained in the study manual. 
 Blinding 
This study will be double-blinded. At all times, treatment and randomization information will be 
kept confidential and will not be released to, the contract research organization (CRO), or the 
sponsor’s study team until database lock of Part A is completed and all safety data has been cleaned 
and monitored. Investigators, subjects and clinical staff will remain blinded throughout the study.  
After Part A, the database will be locked for efficacy assessments in order to evaluate the primary 
efficacy endpoint of the study (percent change from baseline in hand mTLSS at Week 16). After 
the first lock, the sponsor and CRO will be unblinded, but the sites, investigators and subjects, will 
remain blinded to the dose administered. During Part B, the blind (i.e. 40 mg or 80 mg dose) will 
be maintained until the database lock of Part A, however, since the placebo-controlled part of the 
study will have been finalized, with assessment of the primary endpoint and safety done after Part 
A, Part B will be considered as supportive only. A second lock will be done after Part B in order 
to produce the supportive secondary endpoint results for safety and efficacy.  
The safety data from Part A will be cleaned and monitored prior to the unblinding of the sponsor 
and CRO personnel. This process will not involve EDC database lock and interim statistics but 
rather unblinded look of the available data. The sponsor and CRO personnel will remain blinded 
until the last patients of the study complete Week 16 assessments, and data is cleaned and 
monitored. 
Blinding codes should only be broken in emergency situations for reasons of subject safety. If 
unblinding the treatment assignment for a subject is necessary due to a medical emergency (an 
unexpected SAE per product’s safety profile) and other significant medical situations such as 
pregnancy, the investigator can make the decision to unblind the treatment assignment if knowing 
the treatment assignment will help treatment decision of the particular AE. When the blind for a 
subject has been broken, the reason must be fully documented in the source document and 
electronic case report form (eCRF). Whenever possible, the investigator should contact the sponsor 
or its designee before breaking the blind. If the blind is broken, the investigator should promptly 
inform the medical monitor. Documentation of breaking the blind should be recorded with the 
date/time and reason why the blind was broken, and the names of the personnel involved. 
Emergency unblinding details are provided in the study manual. 
The subject for whom the blind has been broken will be discontinued from the study and undergo 
the ET procedures. In cases where there are ethical reasons to have the subject remain in the study, 
the investigator must obtain specific approval from the sponsor or its designee for the subject to 
continue in the study. The primary reason for discontinuation (the event or condition which led to 
the unblinding) will be recorded. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 47 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 Study Treatment Compliance 
Study product compliance will be monitored at each visit. Adherence to treatment will be assessed 
by direct questioning and by maintaining adequate study product dispensing and return records. 
Any deviation from the prescribed dosage regimen will be recorded in the source document. 
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 (OTC) drugs, vitamins, herbal/natural products and 
antacids) taken within 4 weeks prior to screening and throughout the study must be recorded.  
All past and current medication taken by subject to treat CHE (all medication used) and refractory 
moderate potency, high potency and ultra-high potency topical corticosteroids as well as refractory 
systemic corticosteroids (including oral or injectable corticosteroids) will be documented as 
medication history for CHE. The duration of the treatment and the reason for discontinuation will 
be documented.  
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. 
 Comparative Potencies of Topical Corticosteroids 
Ultra-high potency, high potency and moderate potency topical corticosteroids as well as systemic 
corticosteroids (including oral or injectable corticosteroids) used for CHE must be documented as 
per section 6.4. A list of moderate potency, high potency and ultra-high potency topical 
corticosteroids is described in Table 3. 
Table 3 is also intended to be used as a guide for documenting past medication history of the 
subjects on study. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 48 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Table 3. Comparative Potenciesa of Topical Corticosteroids8 
Potency 
Class Topical Corticosteroid 
Formulation 
Ultra-
High 
I 
Betamethasone dipropionate glycol 
0.05% Cream, Ointment, Lotion 
Clobetasol 17-propionate 
0.05% Cream, Foam, Ointment, Lotion, 
Shampoo, Solution 
Halobetasol propionate 
0.05% Ointment 
High 
II 
Amcinonide 
0.1% Ointment 
Betamethasone dipropionate 
0.05% Ointment 
Desoximetasone 
0.25% Cream, Ointment, 0.05% Gel 
Fluocinonide 
0.05% Cream, Ointment, gel 
Halobetasol propionate 
0.05% Cream 
III 
Amcinonide 
0.1% Cream, Lotion 
Betamethasone dipropionate 
0.025% Cream, 0.05% Cream, Lotion 
Betamethasone valerate 
0.1% Ointment, 0.1% Transdermal Patch 
Mometasone furoate 
0.1% Ointment 
Moderate 
IV 
Beclomethasone dipropionate 
0.025% Cream 
Clobetasone 17-butyrate 
0.05% Cream 
Desoximetasone 
0.05% Cream 
Diflucortolone valerate 
0.1% Cream, Ointment 
Fluocinolone acetonide 
0.025% Ointment 
Hydrocortisone 17-valerate 
0.2% Ointment 
Mometasone furoate 
0.1% Cream, Lotion 
Triamcinolone acetonide 
0.1% Cream, Ointment 
V 
Betamethasone valerate 
0.05%, 0.1% Cream, Lotion 
Fluocinolone acetonide 
0.01% Shampoo, Solution 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 49 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Hydrocortisone 17-valerate 
0.2% Cream  
Prednicarbate 
0.1% Cream, Ointment 
Low 
VI 
Desonide 
0.05% Cream, Ointment, Lotion 
VII 
Hydrocortisone 
0.5%, 1%, 2.5% Cream, Ointment, Lotion, 
Solution 
Hydrocortisone acetate 
0.5%, 1% Cream 
aPotency categories are intended to be used as guidelines only. Clinical effectiveness is dependent on many factors 
other than relative potency of the chemical entity. Potency rankings and terminology may differ from one publication 
to another. This table is adapted from the system generally used in the United States and from the World Health 
Organization (WHO) Anatomical Therapeutic Classification system. Assignment of each steroid to a particular 
potency category is based on literature review and is not necessarily the same potency category chosen for that topical 
corticosteroid in other publications using these systems.   
 Permitted Therapies 
6.4.2.1 Emollients 
Subjects must apply an emollient of their choice (except those containing urea or salicylic acid) 
on their hands and feet (if foot eczema is present at screening). The emollient use must be initiated 
at least 1 week prior to Day 1 and subjects must continue using it at the same frequency throughout 
the study until the follow-up visit at Week 36. However, on the day of scheduled visits, subjects 
cannot apply emollient before their scheduled visit time.   
Every effort should be made to keep the same emollient throughout the study. The commercial 
name of the selected emollient(s) will be recorded in the source document and the eCRF. No other 
products may be applied to the lesions during the study. Emollient use will be followed at each 
visit. 
6.4.2.2 Other Permitted Therapies  
The following therapies are permitted: 
• 
Intranasal corticosteroids and inhaled corticosteroids for stable medical conditions are allowed. 
Eye drops containing corticosteroids are allowed.   
• 
Low-dose aspirin  
• 
Use of sunscreen products are permitted when sun exposure cannot be avoided, but sunscreen 
products are prohibited on hands and feet on the day of a scheduled visit prior to the scheduled 
visit time (protective apparel is strongly suggested).  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 50 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 Prohibited Therapies or Procedures 
Table 4 lists prohibited medications are not to be used from the defined washout periods before 
the first administration of study treatment at the Day 1 visit through the last study visit.  
The discretionary use of concomitant treatments or therapies for CHE is prohibited between Day 1 
and Week 8 visit. However, after the Week 8 visit, should subjects experience an exacerbation of 
their CHE that requires, in the opinion of the investigator, the use of a prohibited topical therapy, 
the following approach should be followed:   
1. The investigator needs to discuss the case with the medical monitor in order to obtain 
permission to use a prohibited medication. 
2. Subjects who start prohibited topical medications as a treatment for CHE within the first 
8 weeks of the study will be discontinued from the study product (ASN002 or placebo) and 
will perform the ET visit at the time of discontinuation.  
3. Subjects who start prohibited topical medications as a treatment for CHE after the first 
8 weeks of the study may continue all the study assessments up to the last study visit. Skin 
biopsies will not be performed after the start of a topical medication. 
4. Subjects who start any other prohibited medications or therapies for other reasons may be 
withdrawn from the study, at the investigator’s discretion in agreement with the medical 
monitor and the sponsor. 
 
If in any doubt, investigators are advised to discuss medications with the medical monitor. 






Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 53 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
7.1 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 are discontinued for safety reasons may be asked to come 
for additional follow-up visits, at the investigator’s discretion, after the ET visit to ensure 
appropriate medical care and AEs follow-up. 
Subjects who did not complete the study for reasons other than safety, or have demonstrated 
significant noncompliance to study treatments based on IP accountability (define as subject who 
received < 80% or > 120% of the scheduled doses during the study treatment period) will be 
evaluated by the principal investigator or designee at each visit and may potentially be replaced.  
Subjects who discontinue may be replaced at discretion of the sponsor. 
Reasons for discontinuation include the following: 
• 
The investigator decides that the subject should be withdrawn. If this decision is made because 
of a 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 that has been 
demonstrated to be effective for treatment of the study indication. In this case, discontinuation 
from the study occurs immediately upon introduction of the new agent. 
• 
The subject is lost to follow-up. In this case, a reasonable attempt to contact the subject and 
ascertain his or her status must be made, and these attempts must be documented. 
• 
The subject becomes pregnant at any time during the study.  
• 
Other: 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. 
7.2 Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she fails to return for scheduled visits and is 
unable to be contacted by the study site staff.  
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• 
The site will attempt to contact the subject and reschedule the missed visit. The site will 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 54 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
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. 
8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 Efficacy Assessments 
Clinical evaluations of moderate to severe CHE will be performed by an experienced and qualified 
dermatologist (board certified or equivalent) or other suitably qualified and experienced designee. 
To assure consistency and reduce variability, the same assessor should perform all assessments on 
a given subject whenever possible. 
 Modified Total Lesion Symptom Score 
The modified Total Lesion Symptom Score (mTLSS) will be assessed at the visits specified in 
Table 1. The mTLSS is an assessment of the severity of each of the following: erythema, scaling, 
lichenification/hyperkeratosis, vesicles, oedema, fissures and pruritus/pain. Each of these are rated 
using the 4-point severity scale described in Table 6. Scores will be assigned for the most affected 
side (palmar or dorsal) of the most affected hand identified on Day 1. The same most affected side 
(palmar or dorsal) of the most affected hand will be followed throughout the study. These ratings 
are then added to create a total mTLSS calculated as the sum of assigned individual scores with a 
maximum value of 21 (most severe disease) and a minimum of 0 (no disease).2,5  
For exploratory purposes, a separate mTLSS will be evaluated for the feet for subject for which 
the presence of foot eczema will be documented at the screening and Day 1 visits. Scores will be 
assigned for the most affected side (plantar or dorsal) of the most affected foot.  
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 55 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Table 6. Modified Total Lesion Symptom Score 
Parameter 
Description of Severitya 
Erythema 
0 = Absent 
1 = Faint erythema 
2 = Prominent redness 
3 = Deep intense red colour 
Scaling 
0 = Absent 
1 = Slight flaking over limited areas, mostly fine scales 
2 = Flaking over widespread area(s), coarser scales 
3 = Desquamation covering over 30% of the hand, with coarse thick scales 
Lichenification 
⁄hyperkeratosis 
0 = Absent 
1 = Mild thickening with exaggerated skin lines over limited areas 
2 = Palpable thickening over widespread area(s) 
3 = Prominent thickening over widespread area(s) with exaggeration of normal skin 
markings 
Vesicles 
0 = Absent 
1 = Scattered vesicles affecting up to 10% of hand, without erosion 
2 = Scattered or clustered vesicles affecting up to 30% of hand, without visible 
erosion or excoriation 
3 = High density of vesicles extending over large area(s), or with erosion or 
excoriation 
Oedema  
 
0 = Absent 
1 = Dermal swelling over less than 10% of hands 
2 = Definite dermal swelling over more than 10% of hand 
3 = Dermal swelling with skin induration over widespread area(s) 
Fissures 
0 = Absent 
1 = Cracked skin affecting a small area of the hand 
2 = Cracked skin affecting multiple areas of the hand and causing pain 
3 = One or more deep fissures and causing bleeding or severe pain 
 
Pruritus ⁄pain 
0 = Absent 
1 = Occasional, slight discomfort a few times per day 
2 = Intermittent, causing discomfort frequently during the day 
3 = Persistent or interfering with sleep 
a 0 = absent; 1 = mild; 2 = moderate; 3 = severe. 
 Physician’s Global Assessment 
The Physician’s Global Assessment (PGA)2,5 of disease severity will be assessed at the visits 
specified in Table 1. The PGA is a global assessment of the current state of the disease (moderate 
to severe CHE, hands only; subjects with moderate CHE will be limited to 30% of total 
enrollment). It is a 5-point scale of overall disease severity by rating the particular signs and 
symptoms of CHE (erythema, scaling, hyperkeratosis/lichenification, vesiculation, oedema, 
fissures and pruritus/pain). A detailed description of each PGA severity score is provided in 
Table 7. 
For exploratory purposes, a separate PGA will be evaluated for the feet, for subject for which the 
presence of foot eczema will be documented at the screening and Day 1 visits. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 56 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Table 7. Physician’s Global Assessment 
PGA 
severity 
Features 
Intensity 
Area involveda 
Severe  
(4) 
Erythema, scaling,  
hyperkeratosis ⁄lichenification 
At least one 
moderate or severe 
> 30% of affected 
handb surface 
Vesiculation, oedema, fissures,  
pruritus ⁄pain 
At least one severe 
Moderate  
(3) 
Erythema, scaling,  
hyperkeratosis ⁄lichenification 
At least one mild 
or moderate 
10–30% of affected 
handb surface 
Vesiculation, oedema, fissures,  
pruritus ⁄pain 
At least one 
moderate 
Mild  
(2) 
Erythema, scaling,  
hyperkeratosis ⁄lichenification 
At least one mild 
Less than 10% of 
affected handb surface 
Vesiculation, oedema, fissures,  
pruritus ⁄pain 
At least one mild 
Almost 
clear  
(1) 
Erythema, scaling,  
hyperkeratosis ⁄lichenification 
At least one mild 
Less than 10% of 
affected handb surface 
Vesiculation, oedema, fissures,  
pruritus ⁄pain 
Absent 
Clear  
(0) 
Erythema,scaling,  
hyperkeratosis ⁄lichenification 
Absent 
Not detectable 
Vesiculation, oedema, fissures,  
pruritus ⁄pain 
Absent 
a Area involved does not apply to patients with mostly fingertips eczema. Affected hand surface refers 
to the surface area of the more severely affected side (palmar or dorsal) of the more affected hand. 
b For PGA assessment on feet, % of feet surface is to be used. 
 Extent of Disease 
Extent of disease2,5 will be assessed at the visits specified in Table 1 and will be estimated by the 
physician as the percentage of hand area (palmar and dorsal) affected by eczema, both hands (both 
surface) cumulating 100%.5 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 57 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Presence or absence of foot eczema will be assessed at the visits specified in Table 1 must be 
documented in the source document and eCRF. For exploratory purposes, a separate extent of the 
disease will be evaluated for the feet, for subject for which the presence of foot eczema will be 
documented at the visits specified in Table 1. Percentage will be estimated by the physician as the 
percentage of foot area (plantar and dorsal) affected by eczema, both feet (both surface) cumulating 
100%. 
 Hand Eczema Severity Index  
The HECSI9 will be assessed at the visits specified in Table 1. The HECSI scoring system 
incorporates both the extent and the intensity of the disease. Each hand will be divided into five 
areas [fingertips, fingers (except the tips), palms, back of hands and wrists]. For each of these areas 
the intensity of the six following clinical signs: erythema, induration ⁄ papulation, vesicles, 
fissuring, scaling and oedema will be graded on the following scale: 0, no skin changes; 1, mild 
disease; 2, moderate and 3, severe. For each location (total of both hands) the affected area will be 
given a score from 0 to 4 (0, 0%; 1, 1–25%; 2, 26–50%; 3, 51–75% and 4, 76–100%) for the extent 
of clinical symptoms. Finally, the score given for the extent at each location will be multiplied by 
the total sum of the intensity of each clinical feature, and the total sum called the HECSI score will 
be calculated, varying from 0 to a maximum severity score of 360 points.9 A detailed description 
of the HECSI scoring system is shown in Table 8. 
Table 8. Hand Eczema Severity Index  
Clinical Signs 
Fingertips 
Fingers 
(except tips) 
Palm of 
Hands 
Back of 
Hands 
Wrists 
Erythema (E) 
 
 
 
 
 
Infiltration / Papulation (I) 
 
 
 
 
 
Vesicles (V) 
 
 
 
 
 
Fissures (F) 
 
 
 
 
 
Scaling (S) 
 
 
 
 
 
Oedema (O) 
 
 
 
 
 
SUM (E + I + V + F + S + O) 
 
 
 
 
 
Extent (Ex) 
 
 
 
 
 
Total HECSI score = 
Sum x Ex + 
Sum x Ex + 
Sum x Ex + 
Sum x Ex + 
Sum x Ex  
Total HECSI score (min 0; max 360). For each location (total of both hands) the affected area will be 
given a score from 0 to 4 (0= 0%; 1= 1–25%; 2= 26–50%; 3= 51–75% and 4= 76–100%) for the extent 
of clinical symptoms. Finally, the score given for the extent for each location will be multiplied by the 
total sum of the intensity of each clinical feature (each contributing equally to the final score), and the 
total sum called the HECSI score will be calculated, varying from 0 to a maximum severity score of 360 
points. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 58 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
  Patient Global Assessment  
On the day of the visits specified in Table 1, using the PaGA chart,  subjects will be asked by the 
investigator to grade their overall change from baseline in their CHE by selecting one of the 
following descriptions found in Table 9, which best matches their perception of treatment effect.  
Table 9. Patient Global Assessment2,10 
Cleared or Almost Cleared  
(at least 90% clearing of disease signs and symptoms compared to baseline) 
□ 
Marked improvement (at least 75% clear) 
□ 
Moderate improvement (at least 50% clearing) 
□ 
Mild improvement (at least 25% clearing) 
□ 
No change 
□ 
Worsening 
□ 
8.2 Skin Microbiome analysis 
Collection of skin microbiome samples is a non-invasive procedure where a swab is passed along 
the lesional surface of the palmar aspect (when possible) of the hand with the worst eczema 
involvement, and another swab is passed along a nonlesional area of skin within 5 cm of the 
lesional area. Samples will be collected for all subjects from the same lesional and nonlesional 
areas at Day 1 and Weeks 4, 16 and ET visit (if applicable and occurs prior to Week 16). Skin 
microbiome must be collected prior to the tape stripping and biopsies. 
It is preferred that the microbiome, tape strips and biopsies (if applicable) come from the same 
eczema lesion of the hand. 
Skin microbiome sampling (lesional and non lesional) will also be performed from the plantar 
aspect (when possible) of the foot for the subject’s with foot eczema documented on Day 1 
(preferably same lesion as the one selected for the tape stripping, but adjacent to the tape stripping 
collection area). 
The detailed procedure for collecting skin microbiome samples is provided in the Study Reference 
Manual. 
8.3 Patient Reported Outcomes 
 Work Productivity and Activity Impairment Measure: Specific Health Problem   
The work productivity and activity impairment: specific health problem (WPAI:SHP)11 measure 
will be assessed at the visits specified in Table 1, and evaluated for moderate to severe CHE. It is 
a simple 6-question validated questionnaire that has been used for different health conditions and 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 59 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
customized by replacing the word PROBLEM of the questionnaire by the condition that is studied. 
Its use has been described in many publications, including many multinational studies. The 
customized questionnaire to CHE is provided in APPENDIX A. 
 Dermatology Life Quality Index Questionnaire  
The Dermatology Life Quality Index (DLQI)12 will be assessed for CHE at the visits specified in 
Table 1. It is a simple 10-question validated questionnaire that has been used in more than 40 
different skin conditions. Its use has been described in more than 1,000 publications, including 
many multinational studies. The DLQI is the most frequently used instrument in studies of 
randomized controlled trials in dermatology. The questionnaire is provided in APPENDIX B. 
 Pain Visual Analog Scale 
Pain intensity of the CHE will be recorded at the visits specified in Table 1 using a pain Visual 
Analog Scale (VAS). Pain intensity will be evaluated by asking subjects to place a line 
perpendicular to the VAS line at the point that represents their worst pain intensity over the last 
24 hours.13 The pain VAS, represented in Figure 2, is a scale from 0 to 10, where 0 indicates no 
pain and 10 indicate the worst imaginable pain.13 
 
Figure 2: Pain Visual Analog Scale 
 
 
8.4 Safety Assessments 
 Vital Signs 
The following vital signs will be recorded at the visits specified in Table 1 with the subject in a 
seated position, after having sat calmly for at least 5 minutes: systolic and diastolic blood pressure 
(mmHg), pulse (bpm), and body temperature (°C). 
Weight (kg) and height (cm) will be collected to calculate the BMI and will be recorded at the 
visits specified in Table 1. The height will only be recorded at the screening visit and the same 
value will be used for BMI calculation at other visits. 
Subjects who do not qualify to participate in the study due to a screening vital sign value 
abnormality can repeat the test once within the original screening time window without resulting 
in screen failure, if the investigator believes there is a reasonable possibility that the subject would 
be eligible if re-tested. 
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. 
no pain 
worst imaginable pain 
10 
0 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 60 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 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 hand and foot eczema (if present at screening and baseline)) 
• 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:  
• General appearance 
• Dermatological (except hand and foot eczema (if present at screening and baseline)) 
• 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 




Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 62 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 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 clinically significant findings will be reported as an 
AE. 
8.5 Pharmacokinetic and Pharmacodynamic Assessments 
 Pharmacokinetics Assessment in Blood 
Blood samples will be collected for all subjects for PK analyses of ASN002 on visits and time 
points indicated in the schedule of events in Table 1. Measurement of plasma concentrations of 
ASN002 will be performed in all subjects receiving ASN002 treatment. 
The actual date and time of each blood sample collection will be recorded. Approximately 4 mL 
of blood will be collected for each time point.  
Details about the collection, processing, handling, storage and shipping of blood samples will be 
provided in the laboratory manual. 
Non-compartmental PK analysis will not be performed for this study. 
Population PK analysis will be performed using nonlinear mixed-effects modeling approach with 
first-order conditional methods. This analysis may be combined with PK concentrations from other 
clinical trials in healthy and AD subjects as appropriate. The results from this analysis may be 
reported separately. 
 Skin Biopsies 
At selected study centers, in a subset of approximately 36 subjects who consent to the procedure, 
three or four 2.5-mm skin punch biopsies will be collected at the visits specified in Table 1. Two 
2.5-mm punch biopsies (one from lesional skin and one from adjacent nonlesional skin) will be 
collected from the palmar aspect of the hand at Day 1, and one 2.5-mm punch biopsy will be 
collected from the same lesional skin (outside the scar of the previous biopsy, at least 1 cm away 
from the previous scar) at Week 16 or ET visit (if applicable, and subject is ET prior to Week 16). 
In addition, one 2.5-mm punch biopsy will be collected from the same lesional skin (outside the 
scar of the previous biopsy, at least 1 cm away from the previous scar) at Week 4 in subjects who 
consent to four skin biopsies. Lesional skin biopsies should be as close as possible from the area 
of the skin tape stripping and preferably from the same lesion. 
It is preferred that the microbiome, tape strips and biopsies come from the same eczema lesion of 
the hand. 
Biopsy samples will be obtained from the same subjects who consent to PD samples.  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 63 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
The skin will be cleaned, disinfected, and anesthetized before skin biopsies are performed. Sterile 
gauze will be used to absorb any bleeding. The biopsy sites will be sutured if necessary. 
Details about the collection, processing, handling, storage and shipping of biopsy samples will be 
provided in the laboratory manual. 
 Tape stripping 
For all subjects included on study, superficial skin cells will be collected using tape stripping at 
visits indicated in the schedule of events in Table 1 for gene expression analyses.  
Skin tape stripping samples will be collected on Day 1 (one from lesional skin and one from 
adjacent nonlesional skin) and one at Week 4 and Week 16 (or ET visit, if applicable) (from same 
lesional skin as Day 1). Lesional skin tape stripping samples will be collected for all subjects as 
close as possible to the site of the skin biopsy (if applicable) and preferably from the same lesion. 
For each sampled site, approximately 20 tape strips units will be placed and removed from the 
exact same site one after the other. Tape stripping should be collected prior to study product 
administration and after photographs, if applicable. 
It is preferred that the microbiome, tape strips and biopsies (if applicable) come from the same 
eczema lesion of the hand. 
Tape stripping will also be performed from the plantar aspect (when possible) of the foot for the 
subject’s with foot eczema documented on Day 1 (one from lesional skin and one from adjacent 
nonlesional skin) at Day 1 and one at Week 4 and Week 16 (or ET visit, if applicable) from same 
lesional skin as Day 1. Foot skin tape stripping samples will be collected as close as possible to 
the site of the foot microbiome collection (preferably the same plantar lesion when possible).  
Further instructions regarding collection, handling, storing and shipment of these samples will be 
provided in the laboratory manual.   
 Pharmacodynamics Assessments in Blood 
At selected study centers, for a subset of approximately 36 subjects who consent to the procedure, 
blood samples will be collected for PD analysis on visits indicated in the schedule of events in 
Table 1. PD samples will be drawn as trough samples prior to the study product administration. 
PD samples will be obtained from the same subjects who consent to biopsy collection.  
The actual date and time of each blood sample collection will be recorded. Approximately 8 mL 
of blood will be collected for each time point.  
Details about the collection, processing, handling, storage and shipping of blood samples will be 
provided in the laboratory manual. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 64 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 PK/PD Relationship Assessments  
PK-efficacy, PK-safety and PK-biomarkers relationships will be explored using linear regression, 
loess plots, Hills functions, or logistic regression, as appropriate. The results from these analyses 
may be reported separately. 
8.6 Other Assessments 
 Medical Photography 
At selected study centers, for a subset of approximately 36 subjects who consent to the procedure, 
medical photographs will be performed at the visits specified in Table 1. Medical photographs of 
both aspects (palmar and dorsal) of both hands will be taken to illustrate any visible clinical 
change. Photographs should be taken prior to drug administration, biopsies, tape stripping and 
microbiome sample collection. Care will be taken to use the same camera, the same magnification, 
and the same settings for each photograph at each visit in order to obtain comparable pictures. 
Medical photographs will be taken using a blue background.  
Photographs will be identified and stored as instructed in the photography manual. 
 Body Surface Area (for subjects with AD only) 
For subjects with AD only, their condition will be evaluated based on the diagnostic criteria for 
AD listed in APPENDIX C. The overall Body Surface Area (BSA) affected by AD will be 
evaluated (from 0% to 100%) at the visits specified in Table 1. One subject’s palm with the palmar 
aspect of all fingers represents 1% of his or her total BSA. The BSA will be evaluated to verify 
each subject’s eligibility using the same method as previously described, but excluding hands and 
feet. Subjects with a BSA (excluding hands and feet) of > 15 % at baseline (Day 1) will be excluded 
from the study. The condition will be documented in the eCRF along with the BSA values recorded 
at the visits specified in Table 1. 
 Validated Investigator Global Assessment (for subjects with AD only) 
For subjects with AD only, disease severity (excluding hands and feet) will be assessed at the visits 
specified in Table 1, before the study product administration, using the validated Investigator 
Global Assessment scale for atopic dermatitis (vIGA-AD). The vIGA 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 vIGA scale is provided in APPENDIX D. The condition will be 
documented in the eCRF along with the vIGA scores recorded at the visits specified in Table 1. 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 65 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
8.7 Adverse Events and Serious Adverse Events 
 Definition of Adverse Event  
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
and that does not necessarily have a causal relationship with this treatment. An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a study product, whether or not considered related to 
the study product. AEs and SAEs will be collected from the time of informed consent signature 
until the final visit / contact. 
 Definition of Treatment-Emergent Adverse Event  
A TEAE is any condition that was not present prior to treatment with the study product but 
appeared following treatment, was present at treatment initiation but worsened during treatment, 
or was present at treatment initiation but resolved and then reappeared while the individual was on 
treatment (regardless of the intensity of the AE when the treatment was initiated). 
 Definition of Serious Adverse Event  
A SAE 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 66 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
  Classification of an Adverse Event 
8.7.4.1 Relationship to Study Treatment 
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. 
8.7.4.2 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 67 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
8.7.4.3 Expectedness 
The expectedness of each SAE in relation to the study product will be determined by 
, in 
consultation with the medical monitor and 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, date of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and authority to 
make a diagnosis), and date of resolution/stabilization of the event. All AEs occurring while on 
study must be documented appropriately regardless of relationship.  
Before subject enrollment, study site personnel will note the occurrence and nature of each 
subject’s medical condition(s) in the appropriate section of the source document and eCRF. During 
the study, site personnel will note any change in the condition(s) and the occurrence and nature of 
any AE.  
Any medical condition that is present prior to informed consent signature will be considered as 
part of medical history and not reported as an AE. However, if the study subject’s condition 
deteriorates after the consent signature, it will be recorded as an AE. 
If a subject experiences an AE at any time after the informed consent signature until the end of 
participation in the study, the event will be recorded as an AE in the source document and eCRF. 
Any SAE related to the study participation (e.g., screening procedure) will be recorded in the 
source document and eCRF from the time a subject consents to participate in the study until the 
end of participation in the study. 
The investigator is responsible for appropriate medical care of subjects during the study. The 
investigator also remains responsible for following through with an appropriate health care option 
for all AEs that are ongoing at the end of the study. The subject should be followed until the event 
is resolved or stable. If an AE is ongoing at the end of study, the follow-up duration is left to the 
discretion of the investigator. Follow-up frequency will be performed at the discretion of the 
investigator.  
Whenever possible, clinically significant abnormal laboratory results are to be reported using the 
diagnostic that resulted in the clinically significant abnormal laboratory results and not the actual 
abnormal test. 
Worsening of CHE is captured by efficacy assessments and will not be recorded as an AE.   


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 68 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 Adverse Event Reporting 
Investigators are responsible for monitoring the safety of subjects who are participating in this 
study and for alerting the sponsor to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the subject.  
 Serious Adverse Event Reporting 
 will be the pharmacovigilance unit 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 the 
pharmacovigilance unit (see below contact information) 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: 
 
The pharmacovigilance unit will inform the primary medical monitor, the sponsor, and 
Innovaderm within 1 business day of awareness of a new SAE. The pharmacovigilance unit will 
process and the medical monitor will evaluate all SAEs as soon as the reports are received. For 
each SAE received, the pharmacovigilance unit, in consultation with the medical monitor if 
needed, will make a determination as to whether the criteria for expedited reporting to relevant 
regulatory authorities have been met. The pharmacovigilance unit will manage the expedited 
reporting of relevant safety information to concerned regulatory agencies in accordance with local 
laws and regulations. 
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. 
PPD
PPD


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 69 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
 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 the 
pharmacovigilance unit within 24 hours of confirmation of the pregnancy (contact information to 
be used is the same as for SAE reporting). The pharmacovigilance unit will report all cases of 
pregnancy to the medical monitor, the sponsor, and Innovaderm 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 the 
pharmacovigilance unit and Innovaderm 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. 
 Overdose 
Study product overdose is any accidental or intentional use of study product in an amount higher 
than the dose indicated per protocol for a given subject. Study product compliance (see 
section 6.3.2) should be reviewed to detect potential instances of overdose (intentional or 
accidental). 
Any study product 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 8.7.7, SAEs Reporting, even if the events do not meet 
seriousness criteria. If the AE associated with an overdose does not meet seriousness criteria, it 
must still be reported using the SAEs reporting procedures and in an expedited manner but should 
be noted as non-serious on the form and the Adverse Event eCRF. The excess quantity and duration 
of the overdose should be recorded. 
9 STATISTICAL CONSIDERATIONS  
9.1 Sample Size Determination 
Assuming a common standard deviation of 39% for the percent change-from-baseline mTLSS, a 
difference of 25% and 35% between the 40 mg dose vs. placebo and the 80 mg dose vs. placebo, 
respectively, alpha of 5% (two-sided), 25 patients per group would insure an 80% power to obtain 
a statistically significant treatment effect (using the general F test in an analysis of variance). 
Assuming between 25-30% dropout rates, up to 35 patients per group will be included in this study. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 70 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
9.2 Populations for Analyses 
Efficacy will be evaluated on the basis of the modified intent-to-treat (mITT) analysis set. A 
supportive analysis will also be conducted on the per-protocol (PP) analysis set. 
Modified Intent-to-Treat Population (mITT): This population will include all subjects who 
received at least one dose of the study product. All subjects will be analyzed according to the 
treatment group to which they were randomized. The mITT population will be used as the primary 
analysis population for efficacy. 
The Per-Protocol Population (PP): This population will include all subjects who were randomized, 
who received at least one dose of study product, with no major protocol deviations, and who 
provided evaluable data for the primary endpoint. All subjects will be analyzed according to the 
treatment group that they actually received. 
The Safety Population (SAF): This population will include all subjects who received at least one 
dose of the study product. All subjects will be analyzed according to the treatment group that they 
actually received. 
The PK Population: This population will include all subjects who received at least one dose of 
ASN002 and have plasma concentration data. 
The PD Population: This population will include all subjects who have at least one assessments of 
PD parameters 
9.3 Statistical Analyses 
 General Approach 
Continuous variables will be summarized in tables and will include the number of subjects, mean, 
standard deviation (SD), median, minimum, and maximum. Categorical variables will be presented 
in tables as frequencies and percentages.  
The primary efficacy analysis will be done using the mITT population and the PP population will 
be used as supportive analysis. All efficacy analyses will be performed using Mixed Model 
Repeated Measures (MMRM) analyses as primary analyses to take care of missing observations.  
Additional details regarding the efficacy and safety variable definitions, analyses strategy, control 
of the overall type 1 error, statistical justification, and techniques for handling missing values (e.g. 
for subjects who started prohibited medications) will be detailed in a SAP that will be prepared 
before the database is locked and any analyses are undertaken.  
 Efficacy Analyses 
The primary efficacy endpoint will be analyzed using a repeated measures analysis of covariance 
on percent change-from-baseline variable to compare the time profile between treatments where 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 71 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
the visit will be the time factor (up to Week 16); and the stratification factor PGA score, treatment 
group, and interaction term for treatment-by-visit will be the fixed effects and the baseline value 
will be the covariate. An unstructured variance-covariance matrix will be used. Additional 
interaction terms will also be included in supportive statistical models and will be detailed in the 
SAP. 
A similar approach as for the primary endpoint will be done for all other continuous efficacy 
endpoints.  
For categorical efficacy endpoints involving proportions of PGA (e.g. the proportion of subjects 
achieving at least a 2-grade reduction from baseline to clear (0) or almost clear (1) in PGA at 
week 16), a Cochran Mantel Hansel test (CMH) controlling for PGA at baseline will be performed. 
Overall type 1 error control 
For the primary endpoint of percent change-from-baseline in hand mTLSS at Week 16, a Holm's 
step-down procedure (1979)14 adjustment will be done to test the two comparisons of interest 
(40mg vs. Placebo and 80mg vs. Placebo).  
  Safety Analyses 
All safety data, including AEs and SAEs will be presented and tabulated according to 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 treatment-emergent adverse events (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. Serious adverse events 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 72 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
Results from laboratory analyses, vital signs, and ECGs 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 Drug Dictionary 
(WHO-DD) and listed by subject. Summary of medication classes will also be tabulated.  
No inferential statistics will be done on safety variables. 
 Pharmacokinetic Analyses 
ASN002 concentration data will be listed per subject and summarized descriptively per dose.  
Individual plasma concentration vs. actual time profiles for each subject and treatment, as well as 
the mean (±SD) plasma concentration vs. scheduled time profiles for each dose level, will be 
presented graphically. 
 Pharmacodynamic Analyses 
A biomarker analysis will be performed on blood, tape stripping skin samples and biopsy samples 
collected to evaluate PD effects of ASN002 on inflammatory markers and cell populations. 
Biomarker levels will be compared to placebo adjusted change from baseline over time for each 
treatment group, and the parameters will be summarized by treatment group and overall using 
descriptive statistics.  
 Other Analyses 
Descriptive summaries of baseline characteristics, including demographic data, prior concomitant 
therapy, and of subject disposition will be presented. In addition, a list of subjects who 
discontinued from the study will be provided 
Protocol deviations will be summarized by treatment and category. 
 Planned Interim Analyses 
No interim analysis is planned in this study. However, a primary efficacy analysis of the results 
up to Week 16 visit will be performed after a database lock of all efficacy data of Part A and the 
sponsor will have access to these unblinded results before the study is completed (Week 32).  
Safety data up to Week 16 will be cleaned and monitored prior to unblinding the sponsor. Analysis 
and reporting of the efficacy and safety data will be detailed in the SAP.  
The analysis of the results comprised of Week 16 visit up to Week 32 visit will be considered as 
supportive for the secondary and exploratory objectives of the study. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 73 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
10 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1 
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.   
10.2 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 a research ethics board (REB)/ 
institutional review board (IRB). 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.   
10.3 Informed Consent Process 
An Informed Consent Form describing in detail the study treatment, 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 
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.  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 74 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
The rights and welfare of the subjects will be protected by emphasizing to them that the quality of 
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 REB/IRB. 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. 
10.4 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, 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, Health Canada, and FDA. 
10.5 Confidentiality and Privacy  
Subject confidentiality and privacy are 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 75 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
The study monitor, other authorized representatives of the sponsor, and representatives of the IRB, 
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, institutional policies, or sponsor requirements. 
Skin and blood samples collected during this study will be stored in a secure storage space with 
adequate measures to protect confidentiality. Samples will be stored for up to, but no longer than, 
15 years from the end of the main study after which time the samples will be destroyed. The 
samples will be given a code and neither Asana BioSciences LLC. nor its partners will know the 
subject’s identity. The samples will not be sold to other people or companies. The samples may be 
used when developing new tests, procedures and commercial products. 
10.6 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. 
10.7  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 study site and its facilities.  
The site may be audited, monitored, or inspected by a quality assurance officer named by the 
sponsor, by the REB or IRB, 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 study 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. 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 76 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
10.8 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 
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 electronic data capture 
(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. 
10.9 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 per their policies. The investigator is 
responsible for knowing and adhering to the reviewing IRB/EC requirements.  
10.10 Publication Policy 
The publication policy will be addressed in the Research and Financial Agreement, and all details 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 77 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
outlined in the agreement will apply to this protocol. The trial will be registered on 
ClinicalTrials.Gov prior to the first subject being dosed. 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 78 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
11 REFERENCES 
1. 
Fowler JF, Ghosh A, Sung J, et al. Impact of chronic hand dermatitis on quality of life, 
work productivity, activity impairment, and medical costs. J Am Acad Dermatol. 
2006;54(3):448-457. 
2. 
Ruzicka T, Lynde CW, Jemec GB, et al. Efficacy and safety of oral alitretinoin (9-cis 
retinoic acid) in patients with severe chronic hand eczema refractory to topical 
corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre 
trial. Br J Dermatol. 2008;158(4):808-817. 
3. 
Bissonnette R, Worm M, Gerlach B, et al. Successful retreatment with alitretinoin in 
patients with relapsed chronic hand eczema. Br J Dermatol. 2010;162(2):420-426. 
4. 
Meding B. Epidemiology of hand eczema in an industrial city. Acta Derm Venereol Suppl 
(Stockh). 1990;153:1-43. 
5. 
Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand 
eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20. 
6. 
Kim HL, Jung HJ, Park MY, Youn JI, Ahn JY. Clinical Efficacy of Oral Cyclosporine on 
Intractable Hand Eczema: A Retrospective Review of 16 Cases. Ann Dermatol. 
2018;30(4):475-478. 
7. 
Diepgen TL, Agner T, Aberer W, et al. Management of chronic hand eczema. Contact 
Dermatitis. 2007;57(4):203-210. 
8. 
Corticosteroids: Topical 2018; Comparative potencies Available at: https://www.e-
therapeutics.ca/print/new/documents/MONOGRAPH/en/Corticosteroidstopical, 2018. 
9. 
Held E, Skoet R, Johansen JD, Agner T. The hand eczema severity index (HECSI): a 
scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver 
reliability. Br J Dermatol. 2005;152(2):302-307. 
10. 
Kwon HI, Kim JE, Ko JY, Ro YS. Efficacy and Safety of Alitretinoin for Chronic Hand 
Eczema in Korean Patients. Ann Dermatol. 2016;28(3):364-370. 
11. 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work 
productivity and activity impairment instrument. Pharmacoeconomics. 1993;4(5):353-
365. 
12. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure 
for routine clinical use. Clin Exp Dermatol. 1994;19(3):210-216. 
13. 
Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual Analog 
Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain 
Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain 
Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of 
Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 
2011;63 Suppl 11:S240-252. 
14. 
Holm S. A Simple Sequentially Rejective Multiple Test Procedure. Scandinavian Journal 
of Statistics. 1979;6(2):65-70. 
15. 
Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermato-
Venereologica Supplementum. 1980;92:44-47. 
 
 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 79 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
APPENDIX A: Work Productivity and Activity Impairment 
Questionnaire (WPAI-SHP:CHE) 
Subject ID #: ___ ___ - ___ ___ ___           Subject Initials: ___ ___ ___ 
 
Visit: ___________  
                      Visit Date (dd-mmm-yyyy):______________ 
Section to be completed by site staff 
Work Productivity and Activity Impairment Questionnaire: 
Specific Health Problem V2.0 (WPAI:SHP:CHE) 
 
The following questions ask about the effect of your CHRONIC HAND ECZEMA on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a number, 
as indicated. 
 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check “NO” and skip to question 6. 
 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your CHRONIC HAND ECZEMA?  Include hours you 
missed on sick days, times you went in late, left early, etc., because of your 
CHRONIC HAND ECZEMA.  Do not include time you missed to participate in this 
study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of 
any other reason, such as vacation, holidays, time off to participate in this study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If “0”, skip to question 6.) 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 80 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
5. During the past seven days, how much did your CHRONIC HAND ECZEMA affect 
your productivity while you were working?   
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If CHRONIC HAND ECZEMA affected your work only a little, 
choose a low number.  Choose a high number if CHRONIC HAND ECZEMA 
affected your work a great deal.   
Consider only how much CHRONIC HAND ECZEMA affected  
productivity while you were working. 
CHRONIC 
HAND 
ECZEMA had 
no effect on my 
work 
 
 
 
 
 
 
 
 
 
 
 
CHRONIC HAND 
ECZEMA 
completely 
prevented me 
from working 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
CIRCLE A NUMBER 
 
6. During the past seven days, how much did your CHRONIC HAND ECZEMA affect 
your ability to do your regular daily activities, other than work at a job?   
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If CHRONIC HAND ECZEMA affected your activities only 
a little, choose a low number.  Choose a high number if CHRONIC HAND ECZEMA 
affected your activities a great deal.   
Consider only how much CHRONIC HAND ECZEMA affected your ability  
to do your regular daily activities, other than work at a job. 
 CHRONIC 
HAND 
ECZEMA  had 
no effect on my 
daily activities 
 
 
 
 
 
 
 
 
 
 
 
 CHRONIC 
HAND ECZEMA  
completely 
prevented me 
from doing my 
daily activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
                           
CIRCLE A NUMBER 
 
 
WPAI:SHP:CHE  V2.0 (US English)      
http://www.reillyassociates.net/WPAI_SHP.html   


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 81 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
APPENDIX B: Dermatology Life Quality Index  
 
Subject ID #: ___ ___ - ___ ___ ___        Subject Initials: ___ ___ ___ 
 
Visit: ___________  
                   Visit Date (dd-mmm-yyyy):______________ 
Section to be completed by the site staff 
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 garden? 
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  


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 82 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
If “No,” over the last week how much has your skin been a 
problem at work or studying? 
A lot 
A little 
Not at all  
 
 
 
 
 
 
 
8. Over the last week, how much has your  
skin 
created 
problems with your partner or any of your close friends or 
relatives?  
 
Very much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant  
9. Over the last week, how much has your  
skin 
caused 
any 
sexual difficulties? 
 
Very much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant  
10. Over the last week, how much of a problem has the treatment for 
your skin been, for example by making your home messy, or by 
taking up time? 
Very much 
A lot 
A little 
Not at all 
 
 
 
 
 
 
 
Not relevant  
©AY Finlay, GK Khan, April 1992 www.dermatology.org.uk. 
 
Please check you have answered EVERY question. Thank you. 
 
If two or more questions are left unanswered the questionnaire is not scored. If two or more 
response options are ticked, the response option with the highest score should be recorded. 
If there is a response between two tick boxes, the lower of the two score options should be 
recorded. 
 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 83 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
APPENDIX C: Diagnostic Criteria for Atopic Dermatitis 
Clinical diagnosis of atopic dermatitis according to the criteria of Hanifin and Rajka.15 The criteria 
are as follows: 
 
Major Criteria (must have at least three) 
• Pruritus 
• Typical morphology and distribution: 
– Adults: flexural lichenification or linearity 
– Children and infants: involvement of facial and extensor surfaces 
• Chronic or chronically relapsing dermatitis 
• Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis) 
 
Minor Criteria (must have at least three) 
• Xerosis 
• Ichthyosis/keratosis pilaris/palmar hyperlinearity 
• Immediate (Type 1) skin test reactivity 
• Elevated serum IgE 
• Early age at onset 
• Tendency to skin infections (Staphylococcus aureus, herpes simplex)/impaired cellular 
immunity  
• Tendency to nonspecific hand/foot dermatitis 
• Nipple eczema 
• Cheilitis 
• Recurrent conjunctivitis 
• Dennie-Morgan infraorbital fold 
• Keratoconus 
• Anterior subcapsular cataracts 
• Orbital darkening 
• Facial pallor/erythema 
• Pityriasis alba 
• Anterior neck folds 
• Itch when sweating 
• Intolerance to wool and lipid solvents 
• Perifollicular accentuation 
• Food intolerance 
• Course influenced by environmental/emotional factors 
• White dermographism/delayed blanch 


Asana BioSciences, LLC– Protocol ASN002AD-202 
Page 84 of 84  
Protocol version 6.0: 01 October 2019 
 
 
 
 
 
Confidential and proprietary. Permission should be obtained before any reproduction. 
APPENDIX D: vIGA-ADTM 
 
 

SAP_001.pdf: 






STATISTICAL ANALYSIS PLAN, Version 
Final 1.0 
Protocol Number: ASN002AD-202 V6.0 
Sponsor: Asana BioSciences, LLC 
 
Page 4 of 50 
 
TABLE OF CONTENT 
1 
INTRODUCTION.................................................................................................................... 7 
2 
STUDY OBJECTIVES AND ENDPOINTS .......................................................................... 7 
3 
STUDY DESIGN .................................................................................................................... 10 
3.1 
Overall Design ................................................................................................................ 10 
3.2 
Schedule of Events ......................................................................................................... 13 
3.3 
Treatment ....................................................................................................................... 18 
3.4 
Randomization, Replacement, and Unblinding Procedures ...................................... 18 
3.5 
Changes to the Analysis from the Protocol .................................................................. 19 
4 
POPULATIONS FOR ANALYSIS ...................................................................................... 20 
4.1 
Modified Intent-to-Treat Population ............................................................................ 20 
4.2 
Per-Protocol Population ................................................................................................ 21 
4.3 
Safety Population ........................................................................................................... 21 
4.4 
Pharmacokinetic Population ......................................................................................... 21 
4.5 
Pharmacodynamic Population ...................................................................................... 21 
5 
GENERAL CONSIDERATIONS ........................................................................................ 21 
5.1 
Sample Size ..................................................................................................................... 21 
5.2 
Baseline ........................................................................................................................... 22 
5.3 
Reference Start Date and Analysis Day ....................................................................... 22 
5.4 
Windowing Conventions ................................................................................................ 22 
5.5 
Descriptive Statistics ...................................................................................................... 22 
5.6 
Statistical Tests ............................................................................................................... 22 
5.7 
Handling of Retests, Unscheduled Visits, and Early Termination Data ................... 23 
5.8 
Software Version ............................................................................................................ 23 
6 
STATISTICAL CONSIDERATIONS ................................................................................. 23 
6.1 
Adjustments for Covariates .......................................................................................... 23 
6.2 
Handling of Dropouts or Missing data ......................................................................... 23 
6.3 
Interim Analysis and Data Monitoring ........................................................................ 23 
6.4 
Multicenter Studies ........................................................................................................ 24 
6.5 
Multiple Comparisons/Multiplicity .............................................................................. 24 
6.6 
Examination of Subgroups ............................................................................................ 24 
6.7 
Analysis Presentation ..................................................................................................... 24 
7 
STUDY SUBJECTS ............................................................................................................... 25 
7.1 
Disposition of Subjects ................................................................................................... 25 
7.2 
Protocol Deviations ........................................................................................................ 25 
   	
	

	
PPD


STATISTICAL ANALYSIS PLAN, Version 
Final 1.0 
Protocol Number: ASN002AD-202 V6.0 
Sponsor: Asana BioSciences, LLC 
 
Page 5 of 50 
 
8 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................ 26 
9 
SURGICAL AND MEDICAL HISTORY ........................................................................... 27 
10 
PRIOR AND CONCOMITANT MEDICATIONS ............................................................. 27 
11 
STUDY TREATMENT EXPOSURE AND TREATMENT COMPLIANCE ................. 28 
12 
PHARMACOKINETIC ANALYSIS ................................................................................... 28 
13 
EFFICACY ANALYSIS ........................................................................................................ 30 
13.1 
Primary Efficacy Endpoint ........................................................................................... 30 
Primary Endpoint Analysis ..............................................................................32 
13.2 
Secondary Endpoints ..................................................................................................... 33 
Secondary Endpoint Analyses .........................................................................39 
13.3 
Exploratory Endpoints .................................................................................................. 39 
Extent of Disease .............................................................................................41 
Validated Investigator Global Assessment (for Subjects with AD only)
........................................................................................................42 
Exploratory Analysis .......................................................................................42 
14 
SAFETY ANALYSIS............................................................................................................. 43 
14.1 
Adverse Events ............................................................................................................... 43 
14.2 
Clinical Laboratory ........................................................................................................ 45 
14.3 
Vital Signs ....................................................................................................................... 45 
14.4 
Electrocardiogram (ECG) ............................................................................................. 46 
15 
REFERENCES ....................................................................................................................... 47 
16 
APPENDICES ........................................................................................................................ 48 
 
 
   	
	

	
PPD