Conditions: Atopic Dermatitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 32
Healthy volunteers: no

Brief summary:
This Phase 2a trial will evaluate the effects of EP262 in subjects with atopic dermatitis

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Oral EP262 intervention 2: Placebo
Intervention descriptions: intervention 1: Once daily intervention 2: Once Daily

Protocol document:
Prot_000.pdf: 
Official Title: 
Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects with Atopic 
Dermatitis 
NCT Number: 
NCT06144424 
Document Date: 
EP-262-202 Protocol, Amendment 4.0 (05 April 2024) 
 
 
 


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1.
TITLE PAGE
  
Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate 
the Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects with 
Atopic Dermatitis 
Study Acronym:
EASE
Protocol Number:  
EP-262-202 
  
IND Number: 
166101
Protocol Version Number: 
Amendment 4.0 
Issue Date:
05 April 2024  
Drug Development Phase:
Phase 2a 
Sponsor:
Escient Pharmaceuticals, Inc.
10578 Science Center Drive, Suite 250  
San Diego, CA 92121 USA 
Phone/Fax: +1 (858) 617-8220 
, MD
Escient Pharmaceuticals, Inc.
Phone: 
Confidential Document
All information contained within this protocol is confidential. It may not be 
reproduced, copied, or disseminated in any manner without the prior written consent 
of Escient Pharmaceuticals, Inc. 


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Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate 
the Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects with 
Atopic Dermatitis
Study Acronym:
EASE
Protocol Number:
EP-262-202 
Protocol Version Number: 
Amendment 4.0 
Issue Date:
05 April 2024  
Sponsor Statement
This protocol was subject to critical review and has been approved by the following individuals:  
, MD
  Date
Escient Pharmaceuticals, Inc.
, PhD 
Date
 of Clinical Development
Escient Pharmaceuticals, Inc.
, MS 
  Date
, Biometrics and Data Analytics  
Escient Pharmaceuticals, Inc.


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Investigator’s Agreement
I have read the protocol for EP-262-202 and agree to conduct the study as outlined. I agree to 
maintain the confidentiality of all information received or developed in connection with this 
protocol.  
Printed Name of Investigator 
Signature of Investigator 
Date


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PROTOCOL HISTORY
Document
Amendment Type
Date
Amendment 4.0
Global
05 April 2024
Amendment 3.1
Regional (Canada)
10 March 2024
Amendment 3.0
Global
10 March 2024
Amendment 2.1
Regional (Canada)
14 November 2023
Amendment 2.0
Global
19 October 2023
Amendment 1.1
Regional (Canada)
10 October 2023
Amendment 1.0
Global
02 August 2023
Original Protocol
Not applicable
07 July 2023


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2. 
Synopsis 
Name of Sponsor/Company: 
Escient Pharmaceuticals, Inc. 
Name of Investigational Product: 
EP262 oral capsules 
Study Number: 
EP-262-202 
Phase of Development: 
Phase 2a 
Title of Study: 
Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, 
and Pharmacodynamics of EP262 in Subjects with Atopic Dermatitis  
Study Center(s):  
Multi-center within North America 
Objectives 
Endpoints 
Primary Objective 
To evaluate the safety and tolerability 
of EP262 compared to placebo in 
subjects with atopic dermatitis (AD)  
• 
Type, frequency, and severity of treatment-emergent 
adverse events (TEAEs) 
• 
Change from baseline in vital signs, 
electrocardiograms (ECGs), and clinical laboratory 
parameters 
Secondary Objectives 
To evaluate the pharmacodynamic 
(PD) effects of EP262 compared to 
placebo in subjects with AD on skin 
biopsy-derived biomarkers 
• 
Change from baseline to Week 6 in gene expression 
signature and skin histology (epidermal thickness, 
immune cell infiltration, markers of epidermal 
proliferation) as assessed from biopsies of lesional skin  
Exploratory Objectives 


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Methodology:  
Study EP-262-202 is a Phase 2a, randomized, double-blind, placebo-controlled study to evaluate the 
safety, tolerability, and PD of EP262 over 6 weeks in subjects with AD.  
The study includes a Screening Period of at least a week and up to 30 days to assess subject eligibility 
that includes collection of daily PP-NRS scores; a 6-week Double-Blind Treatment Period; and a 
4-week Follow-Up Period after administration of the last dose of study drug for a total study duration 
of up to approximately 14 weeks for each subject. Approximately 30 subjects will be randomized in a 
2:1 ratio to receive either a 150 mg dose of EP262 or placebo orally (PO), once daily (QD) during the 
6-week Double-Blind Treatment Period. 
EP-262-202 Study Design 
 
PO = oral; QD = once daily. 
a Any subject who completes the Double-Blind Treatment Period or discontinues study drug (EP262 or placebo) 
early will have a Follow-Up Visit approximately 4 weeks (±3 days) after the last dose of study drug. 
Screening Period 
The Screening Period will consist of one visit (Visit 1). During this period, subjects will undergo 
assessments to determine study eligibility per inclusion and exclusion criteria. Visit 1 may be 
conducted over more than 1 day but must be completed between Day -30 and Day -7 (inclusive) to 
allow for collection of a baseline average PP-NRS score. Subjects are to use a protocol-permitted, 
non-urea-containing emollient on lesional and nonlesional skin daily for at least 1 week before Day 1 
and agree to continue using that same emollient daily at the same frequency (ideally once or twice 
daily) throughout the study. Subjects will record emollient use in a daily diary throughout the study. 
Double-Blind Treatment Period  
The Double-Blind Treatment Period will consist of 3 study visits (Visits 2, 3, and 4 [Day 1, Week 3, 
and Week 6]). During this period, all subjects who meet eligibility requirements will be enrolled into 
the study and will be randomized on Visit 2 (Day 1), in a 2:1 ratio, to receive double-blind, PO, QD 
150 mg doses of EP262 or placebo for 6 weeks. Randomization will be conducted centrally via an 
Interactive Web Response System (IWRS). QD PO dosing of study drug should occur after at least a 
4 hour fast and administered at approximately the same time of day. Subjects should refrain from 
eating for at least 2 hours postdose. The time and date of all dose administrations will be recorded in 
a daily diary. The first dose of study drug will be administered at the clinical site on Visit 2 (Day 1) 
after all baseline study procedures are completed. Visit 2 (Day 1) will not have a visit window; all 
other visits in the Double-Blind Treatment Period will have a visit window of ±3 days. Subjects who 
Enroll/Randomize
Visit 2
Day 1
Placebo PO QD (N=10)
Screening
Visit 1
Days -30 to -7
Follow-Up 
Visit 4
Week 6
Screening Period
Double-Blind Treatment Period
Follow-Up Period
150 mg EP262 PO QD (N=20)
Visit 3
Week 3
Visit 5a
Week 10


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discontinue from treatment early should have the Early Treatment Termination Visit conducted as soon 
as possible after the last dose of study drug, ideally within 2 days after the last dose of study drug. 
Follow-Up Period 
Any subject who completes the Double-Blind Treatment Period or discontinues study drug (EP262 or 
placebo) early will have a Follow-Up Visit approximately 4 weeks (±3 days) after the last dose of 
study drug. 
Number of Subjects (Planned): 
Approximately 30 subjects with AD will be randomized in the study.  
Main Criteria for Inclusion and Exclusion: 
Subjects who do not meet the criteria for participation in this study (screen failure) may be rescreened 
once, if deemed acceptable by the Investigator. Subjects who have an exclusionary result during the 
Screening Period (between Visit 1 and Visit 2) may have that assessment repeated once at the 
discretion of the Investigator within the screening window and be enrolled if a repeat assessment is 
within the indicated range as specified below for participating in the study.  
Inclusion Criteria 
To be eligible for study participation, all subjects must meet all of the following inclusion criteria: 
1. Clinically confirmed diagnosis of active AD, according to Hanifin and Rajka criteria (Hanifin 
1980), for at least 1 year, with a BSA of AD involvement of 3% to 20% (excluding palms, soles, 
and scalp) and a vIGA-AD score of ≥3 at Screening and Day 1. Subject should have had no 
significant flares in AD for at least 4 weeks before Screening (based on review of the medical 
chart or directly from the subject) 
2. Has been using a protocol-permitted, non-urea-containing emollient on lesional and nonlesional 
skin daily for at least 1 week before Day 1 and agrees to continue using that same emollient daily 
at the same frequency (ideally once or twice daily) throughout the study  
3. Aged 18 to 80 years, inclusive, at the time of consent 
4. If female, must have a negative serum pregnancy test at Screening, be willing to not donate eggs 
from Screening until 12 weeks after the last dose of study drug, and:  
a. Is surgically sterile; or 
b. Has been amenorrhoeic for ≥1 year without an alternative medical cause; or 
c. If of childbearing potential1, must agree to use 2 forms of contraception, which includes at 
least 1 form of highly effective and 1 effective method2 of contraception from Screening 
until 12 weeks after the last dose of study drug. The following methods can achieve a 
failure rate of less than 1% per year when used consistently and correctly and are 
considered highly effective birth control methods:  
• 
Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation  
• 
Progestogen only hormonal contraception associated with inhibition of ovulation 
 
1 Women of childbearing potential are defined as those who are fertile, following menarche and until becoming 
postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without 
an alternative medical cause. 
2 Effective methods of contraception include barrier methods of contraception (eg, male condom, female condom, 
cervical cap or diaphragm, and contraceptive sponge). 


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• 
Intrauterine device 
• 
Intrauterine hormone releasing system 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner who has received a medical assessment of surgical success  
• 
Sexual abstinence (complete sexual abstinence defined as refraining from heterosexual 
intercourse for the entire period of risk associated with study drug), the reliability of 
which needs to be evaluated in relation to the duration of the clinical study and the 
preferred and usual lifestyle of the subject  
5. If male and is not confirmed surgically sterile, must be willing to not donate sperm and must agree 
to use a barrier method of contraception (eg, condom with spermicide) during intercourse and at 
least 1 other acceptable contraceptive measure for his female partner(s) (eg, hormonal 
contraceptives, intrauterine device, female surgical sterilization, abstinence) from Screening 
through 12 weeks after the last dose of study drug 
6. Must be able to communicate well with the Investigator, understand and comply with the 
requirements of the study, and understand and provide written consent  
Exclusion Criteria 
All subjects meeting any of the following criteria will be excluded from this study: 
1. Other active skin diseases associated with chronic pruritus that might confound the study 
evaluations and results (eg, urticaria, bullous pemphigoid, prurigo nodularis, dermatitis 
herpetiformis) 
2. Clinically infected AD that requires antibiotic therapy 
3. Tattoos or any other markings on any area of the body that might confound the study evaluations 
and results 
4. History of an allergic reaction or significant hypersensitivity to lidocaine or other local anesthetics 
5. History of hypertrophic scarring or keloid formation in scars or suture sites or has a 
contraindication to skin biopsies 
6. Use of the following prohibited AD treatments: 
a. Dupilumab within 26 weeks before Day 1. Other monoclonal antibodies within 4 months 
or 5 half-lives (whichever is longer) before Day 1  
b. Systemic medications that could affect AD, such as retinoids, calcineurin inhibitors, 
hydroxycarbamide (hydroxyurea), azathioprine, systemic corticosteroids, oral janus kinase 
(JAK) inhibitors, hydroxychloroquine, methotrexate, mycophenolate, cyclosporine, or 
cyclophosphamide within 4 weeks before Day 1 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed 
c. Phototherapy (ie, ultraviolet B [UVB], ultraviolet A [UVA]) or sublingual immunotherapy 
within 4 weeks before Day 1 
d. Topical medications that could affect AD, including corticosteroids, calcineurin inhibitors, 
JAK inhibitors, antibiotics and other antimicrobials, products containing urea, or 
phosphodiesterase inhibitors, within 1 week before Day 1. Topical antibiotics may be 
allowed at the skin punch biopsy site only, at the discretion of the Investigator  
e. Systemic antibiotics within 2 weeks before Day 1 
f. Hydroxyzine or diphenhydramine within 1 week before Day 1 
g. Bleach baths within 2 weeks before Day 1 or planned use during the study 


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h. Has had 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 
7. Use of the following prohibited medications within 2 weeks before Day 1: 
a. Drugs that are agonists at the mas-related G protein-coupled receptor X2 (MRGPRX2) 
receptor, including icatibant, opioids (eg, codeine, morphine), clomipramine, or 
nondepolarizing neuromuscular blocking agents (eg, atracurium, rocuronium, vecuronium, 
cisatracurium, mivacurium)  
b. Drugs that inhibit uridine 5’-diphospho-glucuronosyltransferase 1A1 (UGT1A1) 
(eg, atazanavir, canagliflozin, pazopanib, regorafenib, sorafenib, tranilast)  
c. 
d. 
8. Active malignancy or history of malignancy of any organ system (other than localized squamous 
cell or basal cell carcinoma of the skin that have been excised or resolved), treated or untreated, 
within the past 5 years from Screening 
9. Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal, hepatic, 
endocrine (including uncontrolled diabetes mellitus), metabolic, or gastrointestinal disease that, in 
the Investigator’s opinion, would compromise the safety of the subject, interfere with the 
interpretation of the study results, or otherwise preclude subject participation 
10. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect subject 
safety  
11. Any clinically significant abnormalities on screening laboratory tests that, in the opinion of the 
Investigator, precludes participation in the study. The following abnormalities will specifically be 
considered exclusionary: 
a. Bilirubin >upper limit of normal (ULN) and/or any known condition that results in 
abnormal bilirubin elevations or fluctuations (eg, Gilbert’s, Dubin-Johnson, Rotor 
syndrome) 
b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5× ULN 
12. Other co-morbidities that would introduce additional risk factors or interfere with study procedures 
based on clinically significant physical examination, vital sign, standard 12-lead ECG, chemistry, 
hematology, urinalysis, or coagulation results at Screening as deemed by the Investigator  
13. Positive result for human immunodeficiency virus (HIV) or presence of actively replicating viral 
hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at Screening 
14. Significant history of abuse of drugs, solvents, or alcohol within the past year  
15. Participation in any clinical study with an investigational or approved drug/device within 30 days 
or 5 half-lives (whichever is longer) before Day 1 or is planning to participate in another clinical 
study while enrolled in this study 
16. History of known or suspected hypersensitivity to any component of study drug  
17. Female who is pregnant, nursing, or intends to become pregnant during the study 
18. Had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the 
study  
19. Is directly affiliated with the study at the clinical site or is an immediate family member (spouse, 
parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the 
study at the clinical site  


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20. Is employed by Escient Pharmaceuticals, Inc., (that is an employee, temporary contract worker, or 
designee responsible for the conduct of the study) or is an immediate family member of an 
employee of Escient Pharmaceuticals, Inc. 
21. Subject is, in the opinion of the Investigator, not suitable to participate in the study  
Study Drug Materials and Management: 
Study Drug  
Capsules containing 75 mg of EP262 or placebo will be supplied in bottles in a manner to ensure the 
study blind. Each subject will take 2 capsules per dose, with subjects randomized to EP262 receiving a 
total of 150 mg per day.  
Study Drug Packaging and Labeling 
Study drug will be packaged into bottles with child-resistant caps, induction sealed, labeled with a 
unique number, and supplied to clinical sites in a blinded manner.  
Study Drug Storage 
The study drug capsules should be stored at controlled room temperature, 15°C to 25°C (59°F to 
77°F), with excursions up to 30°C (86°F). 
Study Drug Administration  
Each study drug dose is to be administered PO as intact capsules (swallowed whole, not split, opened, 
or chewed) and taken with approximately 240 mL (8 fluid ounces) of water on an empty stomach. 
Subjects will be instructed to take the study drug at approximately the same time of the day after a fast 
of at least 4 hours. Subjects should refrain from eating for at least 2 hours postdose. On the days of 
clinic visits, the time of study drug administration may differ depending on the scheduled visit time. 
The first dose of study drug will be administered at the clinical site on Visit 2 (Day 1) after all baseline 
study procedures are completed.  
Study Drug Dispensing and Accountability 
Subjects will record self-administration of study drug daily in a dosing diary, which will be reviewed 
by clinical site staff at each clinic visit during the Double-Blind Treatment Period following Visit 2. 
Subjects should be instructed to retain the study drug, including the study drug bottle, even if empty, 
and to return it and any remaining study drug to the clinical site during their next visit. The site staff 
should perform study drug accountability and, if applicable, follow-up with the subject to retrieve any 
remaining study drug that has not been returned. 
Key Study Procedures and Safety, Pharmacokinetic, Pharmacodynamic, and Baseline 
Characterization Assessments: 
At specific visits outlined in the Schedule of Assessments (Appendix A), subjects will undergo safety, 
pharmacokinetic (PK), PD, and baseline characterization assessments.  
Key Study Procedures 
Fasting Requirements 
Subjects should fast for at least 8 hours before study visits that require a blood sample for assessment 
of clinical chemistry. Water is acceptable in the morning of clinic visits to ensure the subject is 
hydrated for laboratory sample collection. Subjects should fast at least 4 hours before administration of 
each dose of study drug and refrain from eating for at least 2 hours postdose. Each dose of study drug 
is to be taken with approximately 240 mL (8 fluid ounces) of water on an empty stomach. 


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Discontinuation of Study Drug 
For subjects who terminate treatment with study drug early, regardless of the reason, every effort will 
be made to complete the early treatment termination evaluations as soon as possible after the last dose 
of study drug, ideally within 2 days after the last dose of study drug. 
Whenever possible, subjects should remain in the study and complete the remaining study visits and 
assessments even when study drug has been discontinued. Subjects who discontinue study drug for any 
reason and continue with the study visits as planned through Visit 4 (Week 6) (participating only in PD 
and safety, but not PK measures) will participate in the Follow-Up Visit if the last dose of study drug 
was administered less than 4 weeks before Visit 4 (Week 6) to ensure that at least 4 weeks of follow-up 
data are collected for all randomized subjects. 
If a subject discontinues study drug and chooses not to complete all of the remaining study visits, the 
subject should have the Early Treatment Termination Visit conducted as soon as possible after the last 
dose of study drug, ideally within 2 days after the last dose of study drug, and a Follow-Up Visit 
approximately 4 weeks (±3 days) after the last dose of study drug if at least 4 weeks of follow-up data 
have not already been collected. If a subject fails to attend the Follow-Up Visit and has not withdrawn 
consent, all reasonable efforts will be made to contact the subject to ensure that he/she is in satisfactory 
health. All contacts and contact attempts must be documented in the subject’s medical record. 
Rescue Medications 
New concomitant medications and procedures for treatment of AD are prohibited during the study. If a 
patient requires treatment with a new medication or procedure due to intolerable AD symptoms, study 
drug should be discontinued. Whenever possible, subjects should remain in the study and complete the 
remaining study visits and assessments even when study drug has been discontinued. 
Safety Assessments 
Safety evaluations, including adverse events (AEs), concomitant medications, medical history, vital 
signs, physical examinations, standard 12-lead ECGs, and laboratory evaluations of safety will be 
performed as indicated in the Schedule of Assessments (Appendix A).  
Adverse Event Collection 
AEs will be documented from the signing of the Informed Consent Form (ICF) until the end of study 
participation.  
Pharmacodynamic Assessments 
Skin swabs, skin sample collection via skin tape strips, skin biopsies,
 
 and photographs of 
AD lesions and sites for skin swabs, skin tape strips application, and biopsies will be performed as 
indicated in the Schedule of Assessments (Appendix A). It is preferred that the skin swab, tape strips, 
and biopsies (if applicable) come from the same lesion, if lesion size permits, or from a similar lesion 
in the same anatomical area. 
Examples of the patient-reported assessments are provided in the appendices but are not to be 
distributed to subjects for completion. Subjects will be trained on completion of all patient-reported 
assessments using a study-issued electronic device or application (app). 
Skin Swabs 
A cotton swab will be passed along the lesional skin of the area of worst involvement at Screening. 
The skin swab will be placed in aerobic culture and analyzed for the presence of Staphylococcus 
aureus (S. aureus). At Visits 2, 3, and 4 (Day 1, Week 3, and Week 6), skin swabs will be collected 


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from the same lesional site, even if the lesion has cleared, for assessment of 
. 
Skin swabs are to be collected before skin tape strips application and biopsies when performed on the 
same day. 
Skin Tape Strips 
Commercially available adhesive sheets will be applied on the surface of the skin at predefined areas. 
This procedure will be repeated up to 20 times sequentially on the same area to collect samples from 
the stratum corneum for proteomic assessment. Skin tape strips will be applied to AD lesional skin on 
Visits 2, 3, and 4 (Day 1, Week 3, and Week 6, same location, even if the lesion has cleared), and at a 
nonlesional site at Visit 2 (Day 1). 
Skin Punch Biopsies  
Two 4.0-mm skin biopsies will be collected on Visit 2 (Day 1), one from lesional skin and one from 
nonlesional skin in the vicinity of the lesional skin, and one 4.0-mm skin biopsy will be collected on 
Visit 4 (Week 6) from the same lesional skin, at least 1 cm away from the previous scar, even if the 
lesions have cleared. The effect of EP262 on the gene expression signature and skin histology 
(epidermal thickness, immune cell infiltration, markers of epidermal proliferation) will be evaluated 
via histology, immunohistochemistry, and transcriptomics. The location of the biopsies will be 
1 to 2 cm away from where the skin tape strips were applied, when both are to be performed on the 
same day. If it is not possible to collect the biopsy sample from the same lesion as the tape strips, it 
should be collected from a similar lesion in the same anatomical area. 
Disease Severity  


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Photographs of AD Area 
Representative photographs will be taken of the area of worst lesional involvement at Visit 2 (Day 1) 
and of the same area at Visit 3 (Week 3), Visit 4 (Week 6), and Visit 5 (Follow-Up). Photographs will 
also be taken of areas selected for skin swabs, skin tape strips application, and biopsies before these 
procedures are conducted. 


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Baseline Characterization 
A blood sample will be collected at Visit 2 (Day 1) for measurement of house dust mite 
(HDM)-specific IgE. 
Blood samples will also be taken at Visit 2 (Day 1) for genotyping to evaluate UGT1A1 and filaggrin 
polymorphisms to enable pharmacogenomic analyses.  
Pharmacokinetic Assessment 
Blood sampling will be collected predose (as applicable) at Visit 2 (Day 1), and each visit thereafter to 
analyze trough EP262 concentrations. The EP262 metabolite profile may also be analyzed from these 
trough samples. 
Statistical Methods: 
Descriptive statistics will be presented for study outcome measures, as appropriate. Details will be 
described in the Statistical Analysis Plan (SAP).  
Sample Size Considerations: 
No formal sample size calculation has been made. The sample size has been selected to provide 
adequate information on the safety, tolerability, PK, and PD of EP262 over 6 weeks. 
 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................5 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............15 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................20 
5. 
INTRODUCTION ......................................................................................................23 
5.1. 
Role of the MRGPRX2 Receptor in the Pathogenesis of Atopic Dermatitis .............23 
5.2. 
EP262 and Study Rationale ........................................................................................24 
5.3. 
EP262 Dose Rationale ................................................................................................25 
5.4. 
Summary of Benefits and Risks .................................................................................26 
5.4.1. 
Benefit Summary ........................................................................................................26 
5.4.2. 
Risk Summary ............................................................................................................26 
5.4.3. 
Mitigation Strategy .....................................................................................................27 
5.4.4. 
Overall Benefit:Risk Conclusion ................................................................................27 
6. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................28 
7. 
INVESTIGATIONAL PLAN .....................................................................................28 
7.1. 
Overall Study Design ..................................................................................................28 
7.1.1. 
Screening Period .........................................................................................................29 
7.1.2. 
Double-Blind Treatment Period .................................................................................29 
7.1.3. 
Follow-Up Period .......................................................................................................30 
7.2. 
Start of Study ..............................................................................................................30 
7.3. 
End of Study ...............................................................................................................30 
7.4. 
Number of Subjects ....................................................................................................30 
7.5. 
Dose Adjustment Criteria ...........................................................................................30 
7.6. 
Criteria for Study Termination ...................................................................................30 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................30 
8.1. 
Subject Inclusion Criteria ...........................................................................................31 
8.2. 
Subject Exclusion Criteria ..........................................................................................32 
8.3. 
Study Restrictions .......................................................................................................34 
8.4. 
Concomitant Medications ...........................................................................................34 


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8.4.1. 
Background Therapy ..................................................................................................35 
8.4.2. 
Rescue Medications ....................................................................................................35 
8.5. 
Removal of Subjects from Therapy or Assessment ....................................................35 
8.5.1. 
Discontinuation of Study Drug ...................................................................................35 
8.5.2. 
Discontinuation from the Study ..................................................................................36 
9. 
TREATMENT OF SUBJECTS ..................................................................................37 
9.1. 
Treatment Assignment ................................................................................................37 
9.2. 
Treatment Compliance ................................................................................................37 
9.3. 
Randomization and Blinding ......................................................................................37 
9.3.1. 
Randomization ............................................................................................................37 
9.3.2. 
Blinding ......................................................................................................................37 
9.3.2.1. 
Emergency Unblinding ...............................................................................................37 
9.3.2.2. 
Unblinding for Regulatory Reporting .........................................................................38 
9.4. 
Study Visits .................................................................................................................38 
9.4.1. 
Screening Period .........................................................................................................38 
9.4.1.1. 
Visit 1 (Day -30 to Day -7 [inclusive]) .......................................................................38 
9.4.2. 
Double-Blind Treatment Period .................................................................................39 
9.4.2.1. 
Visit 2 (Day 1) – Enrollment and Randomization ......................................................39 
9.4.2.2. 
Visit 3 (Week 3) ..........................................................................................................40 
9.4.2.3. 
Visit 4 (Week 6) ..........................................................................................................41 
9.4.3. 
Follow-Up Period .......................................................................................................41 
9.4.3.1. 
Visit 5 (Week 10) ........................................................................................................41 
9.4.4. 
Early Treatment Termination Visit .............................................................................42 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................42 
10.1. 
Study Drug ..................................................................................................................42 
10.2. 
Study Drug Packaging and Labeling ..........................................................................43 
10.3. 
Study Drug Storage .....................................................................................................43 
10.4. 
Study Drug Administration.........................................................................................43 
10.4.1. 
Instructions for Missed Dose(s) ..................................................................................43 
10.5. 
Study Drug Dispensing and Accountability ...............................................................43 
10.6. 
Study Drug Handling and Disposal ............................................................................43 
10.7. 
Product Quality Complaints .......................................................................................44 
11. 
SAFETY ASSESSMENTS ........................................................................................44 


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11.1. 
Adverse Events ...........................................................................................................44 
11.1.1. 
Definition of an Adverse Event ..................................................................................44 
11.1.2. 
Determining Severity of Adverse Events ...................................................................45 
11.1.3. 
Determining Causality of Adverse Events .................................................................45 
11.1.4. 
Recording Adverse Events .........................................................................................46 
11.1.4.1. 
Special Instructions for Recording Adverse Events in the eCRF ...............................46 
11.2. 
Serious Adverse Events ..............................................................................................47 
11.2.1. 
Definition of a Serious Adverse Event .......................................................................47 
11.2.2. 
Reporting Serious Adverse Events .............................................................................47 
11.2.3. 
Pregnancy ...................................................................................................................48 
11.3. 
Medical History ..........................................................................................................48 
11.4. 
Vital Signs ..................................................................................................................48 
11.5. 
Body Weight and Height ............................................................................................49 
11.6. 
Physical Examinations ................................................................................................49 
11.7. 
Standard 12-Lead Electrocardiograms .......................................................................49 
11.8. 
Laboratory Evaluations of Safety ...............................................................................49 
11.9. 
Other Laboratory Evaluations .....................................................................................50 
11.10. 
Subject Safety Guidelines ...........................................................................................50 
11.10.1. 
Potential Side Effects ..................................................................................................50 
11.10.2. 
Overdose .....................................................................................................................50 
11.10.3. 
Management of Liver Test Abnormalities ..................................................................50 
12. 
PHARMACODYNAMIC ASSESSMENTS ..............................................................51 
12.1. 
Skin Swabs..................................................................................................................51 
12.2. 
Skin Tape Strips ..........................................................................................................52 
12.3. 
Skin Punch Biopsies ...................................................................................................52 
12.4. 
Disease Severity Scores ..............................................................................................52 
12.5. 
Pruritus ........................................................................................................................53 
12.6. 
Disease Control ...........................................................................................................53 


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12.7. 
Quality of Life ............................................................................................................53 
12.9. 
Photographs of AD Area ............................................................................................54 
13. 
BASELINE CHARACTERIZATION ........................................................................54 
14. 
PHARMACOKINETICS ASSESSMENT .................................................................54 
15. 
STATISTICS ..............................................................................................................54 
15.1. 
Analysis Sets ...............................................................................................................55 
15.2. 
Sample Size Considerations .......................................................................................55 
15.3. 
Subject Disposition .....................................................................................................55 
15.4. 
Demographics and Baseline Characteristics ...............................................................55 
15.5. 
Study Drug Usage and Compliance ............................................................................55 
15.6. 
Safety Analysis ...........................................................................................................55 
15.7. 
Pharmacodynamic Analysis........................................................................................56 
15.8. 
Pharmacokinetic Analysis ..........................................................................................56 
15.9. 
Subgroup Analyses .....................................................................................................56 
15.10. 
Multiple Comparison/Multiplicity ..............................................................................56 
15.11. 
Planned Interim Analysis ............................................................................................56 
16. 
QUALITY CONTROL AND DATA MANAGEMENT ...........................................57 
16.1. 
Data Quality Assurance ..............................................................................................57 
16.2. 
Data Management .......................................................................................................57 
16.3. 
Monitoring ..................................................................................................................57 
16.4. 
Confidentiality and Auditing ......................................................................................58 
16.5. 
Case Report Forms .....................................................................................................58 
16.6. 
Source Documents ......................................................................................................58 
16.7. 
Records Retention .......................................................................................................58 
16.8. 
Informed Consent .......................................................................................................59 
16.9. 
Ethical Conduct of the Study ......................................................................................59 
16.10. 
Institutional Review Board/Independent Ethics Committee ......................................59 
17. 
STUDY MANAGEMENT .........................................................................................60 
17.1. 
Protocol Deviations ....................................................................................................60 
17.2. 
Publications .................................................................................................................60 


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17.3. 
Change in Clinical Site Staff ......................................................................................60 
18. 
LIST OF REFERENCES ............................................................................................61 
APPENDIX A. SCHEDULE OF ASSESSMENTS ...................................................................65 
APPENDIX B. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS ..........69 
APPENDIX H. SUMMARY OF CHANGES BY AMENDMENT ...........................................79 
 
LIST OF FIGURES 
Figure 1: 
EP-262-202 Study Design ..........................................................................................29 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................20 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
AD 
atopic dermatitis 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
app 
application 
AST 
aspartate aminotransferase 
ATC 
Anatomic Therapeutic Chemistry 
BCRP 
breast cancer resistance protein 
BSA 
Body Surface Area  
CFR 
Code of Federal Regulations 
Cmax 
maximum observed concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
 
 
 
 
ECG  
electrocardiogram 
eCRF 
electronic case report form 
EGF 
epidermal growth factor 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HDM 
house dust mite 
HEENT 
head, eyes, ears, nose, throat 
HIV 
human immunodeficiency virus 


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Abbreviation or Specialist Term 
Explanation 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IgE 
immunoglobulin E 
IgG 
immunoglobulin G 
IL 
interleukin 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IWRS 
Interactive Web Response System 
JAK 
janus kinase 
MATE 
multidrug and toxin extrusion 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRGPR 
mas-related G protein-coupled receptor 
NOAEL 
no-observed-adverse-effect-level 
OATP 
organic anion transporting polypeptide 
P-gp 
P-glycoprotein 
PD 
pharmacodynamic(s) 
PK 
pharmacokinetic(s) 
PO 
oral 
PP 
Per Protocol 
 
 
PQC 
product quality complaint 
QC 
quality control 
QD 
once daily 
 
 
SAE 
serious adverse event 
SAER 
Serious Adverse Event Report 
SAP 
Statistical Analysis Plan 
S. aureus 
Staphylococcus aureus 
SEB 
Staphylococcus aureus Enterotoxin Type B 
SOC 
System Organ Class 
SOP 
standard operating procedure 


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Abbreviation or Specialist Term 
Explanation 
t1/2 
half-life 
TEAE 
treatment-emergent adverse event 
Th2 
type 2 T helper cells 
Tmax 
time to reach maximum observed concentration 
TNF-α 
tumor necrosis factor-alpha 
 
 
UGT1A1 
uridine 5’-diphospho-glucuronosyltransferase 1A1 
ULN 
upper limit of normal 
UVA 
ultraviolet A 
UVB 
ultraviolet B 
US 
United States 
 
 
WHO 
World Health Organization 


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5. 
INTRODUCTION 
5.1. 
Role of the MRGPRX2 Receptor in the Pathogenesis of Atopic 
Dermatitis 
Atopic dermatitis (AD) is a common, chronic inflammatory skin disease characterized by 
impaired barrier function, eczematous dermatitis, and chronic itch (Magnifico 2020, Yu 2021). 
Skin thickening, lichenification of the skin from chronic scratching, erythema, and acute lesions 
may develop over time (Correale 1999). Disease symptoms are often exacerbated by external 
factors, including bacterial colonization on the skin, various environmental stimuli including heat 
and sweating, as well as exposure to aeroallergens such as house dust mites (HDMs). In addition 
to these external factors, impaired epidermal skin barrier function is believed to be an important 
factor in the pathogenesis of AD, including genetic mutations in filaggrin, decreased filaggrin 
expression, and dysregulation of the immune system leading to cellular infiltrates including 
dendritic cells, type 2 T helper cells (Th2), and eosinophils in the skin. The prevalence of AD in 
adults has been estimated to be 7% to 10% in the United States (US) and 4.4% to 7.1% in Europe 
(Eckert 2019, Hadi 2021). 
The mas-related G protein-coupled receptor (MRGPR) family is comprised of 8 human Class A 
rhodopsin-like G-protein coupled receptors (MRGPRX1-X4 and D-G) that can sense noxious 
stimuli and appear to have a role in innate immunity. MRGPRX2 is predominantly expressed in 
mast cells and has been shown to induce degranulation upon binding to a wide variety of 
agonists (Subramanian 2016, Corbiere 2021). MRGPRX2 has been shown to mediate 
immunoglobulin E (IgE)-independent activation of mast cells, including degranulation and 
regulation of inflammatory processes. Activation of MRGPRX2 triggers release of 
proinflammatory mediators and a multicellular signaling cascade that likely plays a key role in 
multiple human diseases involving clinically relevant mast cell activation (Babina 2020, 
Thapaliya 2021), including AD. 
Mast cells and MRGPRX2 have been implicated in the pathophysiology of AD in both clinical 
and preclinical studies. A significant association has been observed between the number of mast 
cells in AD skin lesions and the disease severity (assessed by the Eczema Area and Severity 
Index [EASI] score) (Simon 2004). Increased expression of the MRGPRX2 agonist substance P, 
as well as MRGPRX2, has been reported in itchy AD patient skin versus non-itchy skin samples 
(Nattkemper 2018, Youngblood 2020). In addition to substance P, MRGPRX2 is also activated 
by multiple eosinophil granule proteins, including major basic protein and eosinophil cationic 
protein fragments. Elevated levels of these peptides in serum of patients with AD have been 
reported and are correlated to severity of disease (Kapp 1991, Morita 1995, Ogasawara 2020, 
Deeks 2021). An attenuated phenotype has been shown in Mrgprb2 knockout mice (the murine 
homolog of MGRPRX2) in a preclinical model of AD induced by treatment with delta-toxin, an 
MRGPRX2 agonist released by Staphylococcus aureus (S. aureus), and HDM extract including a 
reduction in Th2 cytokines, improved epidermal integrity, improved clinical scores, and reduced 
local skin inflammation (Serhan 2019). This reduction of phenotype in Mrgprb2 knockout mice 
was also observed in other models of dermatitis (Green 2019, Meixiong 2019, Corbiere 2021). 
Collectively, these findings point to a key role of MRGPRX2 in mediating IgE-independent mast 
cell activation and skin inflammation, making this receptor a promising novel target for AD as 


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well as numerous urticarial, inflammatory, and pain conditions that are precipitated by 
degranulation of mast cells and not adequately addressed by available treatments. 
5.2. 
EP262 and Study Rationale 
EP262 is a potent small-molecule antagonist of the human MRGPRX2 receptor under 
development as an orally (PO) administered therapy for AD and chronic spontaneous urticaria.  
Results from Study EP-262-101, a first-in-human randomized, Phase 1 clinical study of single 
and multiple daily PO doses of EP262 or placebo in 64 healthy subjects, have provided 
information on the safety, tolerability, and pharmacokinetics (PK) of EP262. Study EP-262-101 
also included an initial food effect evaluation. Thirty healthy subjects received a single 50, 150, 
400, 800, or 1200 mg dose of EP262. Eighteen subjects received 50, 150, or 300 mg as a 
multiple dose regimen over 7 days. 
All doses evaluated were well tolerated with no dose-limiting adverse events (AEs), early 
terminations due to AEs, moderate or severe AEs, or serious AEs (SAEs) reported with EP262. 
No adverse trends in safety laboratory measures, vital signs, or electrocardiogram (ECG) 
parameters have been observed. EP262 concentrations increased with increasing single doses in 
an approximately linear manner and modeling of single dose data predicted multiple dose 
concentrations. 
 
 
 
 
 
 
EP262 was evaluated in MRGPRX2 knock-in mice expressing the human receptor in a 
translational model of AD induced by cutaneous exposure to HDM extracts and S. aureus 
Enterotoxin Type B (SEB). In initial experiments, daily PO administration of EP262 
significantly attenuated the development of AD relative to vehicle controls as measured by visual 
scoring, tissue measurements, and histopathology following exposure to HDM/SEB (Wollam 
2023). As a proof-of-concept study, Study EP-262-202 aims to confirm these findings in human 
disease, focusing on mechanistic measures and objective assessments of early changes in lesional 
AD skin. Study EP-262-202 will evaluate the safety, tolerability, and pharmacodynamics (PD) of 
EP262 over 6 weeks of treatment in subjects with AD. The 6-week treatment duration is 
supported by the 6-week GLP toxicology program and deemed sufficient to demonstrate changes 
in PD measures and to provide trends in efficacy based on the anticipated rapid onset of action of 
EP262 to directly block activation of MRGPRX2. 
The primary objective is to evaluate the safety and tolerability of EP262 in patients with AD, 
which will be measured by type, frequency, and severity of treatment-emergent AEs (TEAEs), 
and change from baseline in vital signs, ECGs, and clinical laboratory parameters. In addition to 
evaluations of safety and tolerability, changes in differentially expressed genes from biopsies of 
lesional skin relative to nonlesional skin will be assessed before and after treatment. The effect of 
EP262 on AD skin lesions will also be assessed via histology, including examinations of 
epidermal thickness, immune cell infiltration, and markers of epidermal proliferation and skin 
barrier integrity. Notably, early transcriptomic and histologic changes in lesional skin have been 


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demonstrated to correspond with improvements in clinical scores (Hamilton 2014, Bissonnette 
2019, Pavel 2019), potentially serving as initial indicators of treatment response. 
Disease severity will be evaluated 
 
 Although the 
study is not powered to detect significant changes in these clinical scores versus placebo, they 
are included to assess trends in improvement and enable analyses of the correlation between 
transcriptomic and clinical changes. Additionally, pruritus, disease control, and quality of life 
will be evaluated through the
 
. Other exploratory 
analyses include
 
 
  
The study will be randomized to ensure random allocation of subjects to treatment arms and 
reduce bias. Because several of the PD assessments have a high degree of subjectivity, the study 
will be double-blinded. In addition, a placebo-controlled design will be used to control for 
confounding factors, such as potential Investigator bias, and to ensure that the statistical 
procedures can be appropriately applied. 
5.3. 
EP262 Dose Rationale 
The 150 mg EP262 dose level to be evaluated in Study EP-262-202 was selected based on a 
variety of factors to maximize efficacy without adversely impacting safety, including results 
from nonclinical pharmacology studies, nonclinical toxicology studies, and results from 
Study EP-262-101, a Phase 1 first in human clinical study in healthy subjects.  


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5.4. 
Summary of Benefits and Risks 
5.4.1. 
Benefit Summary 
While it is currently uncertain whether patients with AD will benefit from treatment in this study, 
nonclinical in vitro and in vivo data, as well as scientific publications implicating MRGPRX2 as 
a mediator of mast cell degranulation and associated inflammation (Kapp 1991, Morita 1995, 
Nakamura 2013, Azimi 2017, Nattkemper 2018, Green 2019, Meixiong 2019, Serhan 2019, 
Ogasawara 2020, Wang 2020, Youngblood 2020, Corbiere 2021), provide compelling support 
that EP262 has the potential to be an effective treatment for patients with AD. 
5.4.2. 
Risk Summary  
The doses evaluated in Study EP-262-101 were well tolerated with no dose-limiting AEs, early 
terminations due to AEs, moderate or severe AEs, or SAEs reported with EP262. Additionally, 
no adverse trends in safety laboratory measures, vital signs, or ECGs were observed.  
In conventional nonclinical safety assessments, no adverse toxicological findings were observed 
at plasma concentrations well above those estimated to be required for robust pharmacologic 
activity. 
 
 
 
 
 
 
 
 
 
 


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5.4.3. 
Mitigation Strategy 
For this initial clinical proof-of-concept study, subjects with clinically significant co-morbidities 
such as hepatic, renal, or cardiovascular disease will be excluded.  
Routine safety measures have been incorporated into the protocol, including AE reviews, vital 
sign and 12-lead ECG assessments, and laboratory evaluations, including monitoring of bilirubin 
and management of liver test abnormalities (Section 11.10.3).  
5.4.4. 
Overall Benefit:Risk Conclusion 
Overall, the clinical and nonclinical experience to date with EP262 suggests minimal risk to 
subjects participating in Study EP-262-202. Importantly, there is a clear unmet need for novel 
treatment options for AD. The first-line therapeutic approach for management of AD includes a 
combination of emollients, antibiotics, anti-pruritic, and topical anti-inflammatory therapies 
(Sahni 2022). Dupilumab and tralokinumab, injectable monoclonal antibodies that block receptor 
binding of interleukin (IL)-4 and/or IL-13 (reducing Th2 response), have been approved for the 
treatment of moderate-to-severe AD as second-line therapy (Tameez Ud Din 2020, Blair 2022). 
Oral janus kinase (JAK) inhibitors (abrocitinib and upadacitinib) have recently been approved 
for treatment of AD, but have several serious side effects and are indicated as third-line therapy 
only (in adults with refractory, moderate-to-severe AD whose disease is not adequately 
controlled with other systemic drug products, including biologics, or when use of those therapies 


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is inadvisable) (Mikhaylov 2023). If determined to be effective, EP262 may ultimately have the 
potential to offer a much-needed additional treatment option for patients with AD. 
6. 
TRIAL OBJECTIVES AND PURPOSE 
Objectives 
Endpoints 
Primary Objective 
To evaluate the safety and tolerability of 
EP262 compared to placebo in subjects 
with AD  
• 
Type, frequency, and severity of TEAEs 
• 
Change from baseline in vital signs, ECGs, and clinical 
laboratory parameters 
Secondary Objectives 
To evaluate the PD effects of EP262 
compared to placebo in subjects with AD 
on skin biopsy-derived biomarkers 
• 
Change from baseline to Week 6 in gene expression 
signature and skin histology (epidermal thickness, 
immune cell infiltration, markers of epidermal 
proliferation) as assessed from biopsies of lesional skin 
Exploratory Objectives 
7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
Study EP-262-202 is a Phase 2a, randomized, double-blind, placebo-controlled study to evaluate 
the safety, tolerability, and PD of EP262 over 6 weeks in subjects with AD.  
The study includes a Screening Period of at least a week and up to 30 days to assess subject 
eligibility that includes collection of daily PP-NRS scores; a 6-week Double-Blind Treatment 
Period; and a 4-week Follow-Up Period after administration of the last dose of study drug for a 
total study duration of up to approximately 14 weeks for each subject (Figure 1). Approximately 


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30 subjects will be randomized in a 2:1 ratio to receive either a 150 mg dose of EP262 or placebo 
PO, once daily (QD) during the 6-week Double-Blind Treatment Period. 
Figure 1: 
EP-262-202 Study Design 
 
PO = oral; QD = once daily. 
a Any subject who completes the Double-Blind Treatment Period or discontinues study drug (EP262 or placebo) 
early will have a Follow-Up Visit approximately 4 weeks (±3 days) after the last dose of study drug. 
7.1.1. 
Screening Period 
The Screening Period will consist of one visit (Visit 1). During this period, subjects will undergo 
assessments to determine study eligibility per inclusion and exclusion criteria. Visit 1 may be 
conducted over more than 1 day but must be completed between Day -30 and Day -7 (inclusive) 
to allow for collection of a baseline average PP-NRS score. Subjects are to use a protocol-
permitted, non-urea-containing emollient on lesional and nonlesional skin daily for at least 
1 week before Day 1 and agree to continue using that same emollient daily at the same frequency 
(ideally once or twice daily) throughout the study. Subjects will record emollient use in a daily 
diary throughout the study. 
7.1.2. 
Double-Blind Treatment Period 
The Double-Blind Treatment Period will consist of 3 study visits (Visits 2, 3, and 4 [Day 1, 
Week 3, and Week 6]). During this period, all subjects who meet eligibility requirements will be 
enrolled into the study and will be randomized on Visit 2 (Day 1), in a 2:1 ratio, to receive 
double-blind, PO, QD 150 mg doses of EP262 or placebo for 6 weeks. Randomization will be 
conducted centrally via an Interactive Web Response System (IWRS). QD PO dosing of study 
drug should occur after at least a 4 hour fast and administered at approximately the same time of 
day. Subjects should refrain from eating for at least 2 hours postdose. The time and date of all 
dose administrations will be recorded in a daily diary. The first dose of study drug will be 
administered at the clinical site on Visit 2 (Day 1) after all baseline study procedures are 
completed. Visit 2 (Day 1) will not have a visit window; all other visits in the Double-Blind 
Treatment Period will have a visit window of ±3 days. Subjects who discontinue from treatment 
early should have the Early Treatment Termination Visit conducted as soon as possible after the 
last dose of study drug, ideally within 2 days after the last dose of study drug.  
Enroll/Randomize
Visit 2
Day 1
Placebo PO QD (N=10)
Screening
Visit 1
Days -30 to -7
Follow-Up 
Visit 4
Week 6
Screening Period
Double-Blind Treatment Period
Follow-Up Period
150 mg EP262 PO QD (N=20)
Visit 3
Week 3
Visit 5a
Week 10


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7.1.3. 
Follow-Up Period 
Any subject who completes the Double-Blind Treatment Period or discontinues study drug 
(EP262 or placebo) early will have a Follow-Up Visit approximately 4 weeks (±3 days) after the 
last dose of study drug. 
7.2. 
Start of Study 
A subject is considered to have started the study when the subject signs his/her first informed 
consent to participate in the clinical study. 
The start of the study is the date of when the first subject signs his/her first informed consent to 
participate in the clinical study. 
7.3. 
End of Study 
A subject is considered to have completed the study if he/she has completed all phases of the 
study, including the last study visit (ie, the Follow-Up Visit [Visit 5]). 
The end of the study is defined as the date of the last study visit of the last subject in the study 
globally. The end of study may result from the completion of the study according to the protocol 
or due to early termination by the Sponsor or at the request of a regulatory agency, Institutional 
Review Board (IRB), or Independent Ethics Committee (IEC) (Section 7.6).  
7.4. 
Number of Subjects 
Approximately 30 subjects with AD will be randomized in the study.  
7.5. 
Dose Adjustment Criteria 
The dosage for study drug should be maintained constant during the study. However, dosing of 
study drug may be interrupted or discontinued due to safety findings. Refer to Section 8.5 for 
guidance on mandatory discontinuation of study drug due to safety findings and Section 11.10.3 
for guidance on study drug interruption due to liver test abnormalities. 
7.6. 
Criteria for Study Termination 
The Sponsor may terminate the study at a clinical site at any time (eg, Good Clinical Practice 
[GCP] noncompliance or poor study data quality). The entire study may also be terminated by 
the Sponsor or at the request of a regulatory agency, IRB, or IEC. If instructed by the Sponsor or 
designee, the Investigator must implement the termination of the study in a timeframe to ensure 
subject safety and well-being. Refer to Section 8.5.2 (Discontinuation from the Study) for 
instructions for subjects whose participation from the study is discontinued. 
The Investigator and/or Sponsor (or designee) must notify the IRB/IEC of discontinuation of a 
site or the study and the reason for doing so. 
8. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
Subjects who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once, if deemed acceptable by the Investigator. Subjects who have an exclusionary 


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result during the Screening Period (between Visit 1 and Visit 2) may have that assessment 
repeated once at the discretion of the Investigator within the screening window and be enrolled if 
a repeat assessment is within the indicated range as specified below for participating in the study. 
8.1. 
Subject Inclusion Criteria 
To be eligible for study participation, all subjects must meet all of the following inclusion 
criteria: 
1. Clinically confirmed diagnosis of active AD, according to Hanifin and Rajka criteria 
(Hanifin 1980), for at least 1 year, with a BSA of AD involvement of 3% to 20% 
(excluding palms, soles, and scalp) and a vIGA-AD score of ≥3 at Screening and Day 1. 
Subject should have had no significant flares in AD for at least 4 weeks before Screening 
(based on review of the medical chart or directly from the subject) 
2. Has been using a protocol-permitted, non-urea-containing emollient on lesional and 
nonlesional skin daily for at least 1 week before Day 1 and agrees to continue using that 
same emollient daily at the same frequency (ideally once or twice daily) throughout the 
study  
3. Aged 18 to 80 years, inclusive, at the time of consent 
4. If female, must have a negative serum pregnancy test at Screening, be willing to not 
donate eggs from Screening until 12 weeks after the last dose of study drug, and:  
a. Is surgically sterile; or 
b. Has been amenorrhoeic for ≥1 year without an alternative medical cause; or 
c. If of childbearing potential3, must agree to use 2 forms of contraception, which 
includes at least 1 form of highly effective and 1 effective method4 of contraception 
from Screening until 12 weeks after the last dose of study drug. The following 
methods can achieve a failure rate of less than 1% per year when used consistently 
and correctly and are considered highly effective birth control methods: 
• Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation  
• Progestogen only hormonal contraception associated with inhibition of ovulation 
• Intrauterine device 
• Intrauterine hormone releasing system 
• Bilateral tubal occlusion 
• Vasectomized partner who has received a medical assessment of surgical success  
• Sexual abstinence (complete sexual abstinence defined as refraining from 
heterosexual intercourse for the entire period of risk associated with study drug), 
 
3 Women of childbearing potential are defined as those who are fertile, following menarche and until becoming 
postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without 
an alternative medical cause. 
4 Effective methods of contraception include barrier methods of contraception (eg, male condom, female condom, 
cervical cap or diaphragm, and contraceptive sponge). 


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the reliability of which needs to be evaluated in relation to the duration of the 
clinical study and the preferred and usual lifestyle of the subject  
5. If male and is not confirmed surgically sterile, must be willing to not donate sperm and 
must agree to use a barrier method of contraception (eg, condom with spermicide) during 
intercourse and at least 1 other acceptable contraceptive measure for his female partner(s) 
(eg, hormonal contraceptives, intrauterine device, female surgical sterilization, 
abstinence) from Screening through 12 weeks after the last dose of study drug 
6. Must be able to communicate well with the Investigator, understand and comply with the 
requirements of the study, and understand and provide written consent  
8.2. 
Subject Exclusion Criteria 
All subjects meeting any of the following criteria will be excluded from this study: 
1. Other active skin diseases associated with chronic pruritus that might confound the study 
evaluations and results (eg, urticaria, bullous pemphigoid, prurigo nodularis, dermatitis 
herpetiformis) 
2. Clinically infected AD that requires antibiotic therapy 
3. Tattoos or any other markings on any area of the body that might confound the study 
evaluations and results 
4. History of an allergic reaction or significant hypersensitivity to lidocaine or other local 
anesthetics 
5. History of hypertrophic scarring or keloid formation in scars or suture sites or has a 
contraindication to skin biopsies 
6. Use of the following prohibited AD treatments: 
a. Dupilumab within 26 weeks before Day 1. Other monoclonal antibodies within 
4 months or 5 half-lives (whichever is longer) before Day 1  
b. Systemic medications that could affect AD, such as retinoids, calcineurin inhibitors, 
hydroxycarbamide (hydroxyurea), azathioprine, systemic corticosteroids, oral JAK 
inhibitors, hydroxychloroquine, methotrexate, mycophenolate, cyclosporine, or 
cyclophosphamide within 4 weeks before Day 1 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear 
drops containing corticosteroids are also allowed 
c. Phototherapy (ie, ultraviolet B [UVB], ultraviolet A [UVA]) or sublingual 
immunotherapy within 4 weeks before Day 1 
d. Topical medications that could affect AD, including corticosteroids, calcineurin 
inhibitors, JAK inhibitors, antibiotics and other antimicrobials, products containing 
urea, or phosphodiesterase inhibitors, within 1 week before Day 1. Topical antibiotics 
may be allowed at the skin punch biopsy site only, at the discretion of the Investigator 
e. Systemic antibiotics within 2 weeks before Day 1 
f. Hydroxyzine or diphenhydramine within 1 week before Day 1 
g. Bleach baths within 2 weeks before Day 1 or planned use during the study 


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h. Has had 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 
7. Use of the following prohibited medications within 2 weeks before Day 1: 
a. Drugs that are agonists at the MRGPRX2 receptor, including icatibant, opioids 
(eg, codeine, morphine), clomipramine, or nondepolarizing neuromuscular blocking 
agents (eg, atracurium, rocuronium, vecuronium, cisatracurium, mivacurium)  
b. Drugs that inhibit UGT1A1 (eg, atazanavir, canagliflozin, pazopanib, regorafenib, 
sorafenib, tranilast) 
c. 
d. 
8. Active malignancy or history of malignancy of any organ system (other than localized 
squamous cell or basal cell carcinoma of the skin that have been excised or resolved), 
treated or untreated, within the past 5 years from Screening 
9. Evidence of clinically significant cardiac, neurologic, psychiatric, pulmonary, renal, 
hepatic, endocrine (including uncontrolled diabetes mellitus), metabolic, or 
gastrointestinal disease that, in the Investigator’s opinion, would compromise the safety 
of the subject, interfere with the interpretation of the study results, or otherwise preclude 
subject participation 
10. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may 
affect subject safety  
11. Any clinically significant abnormalities on screening laboratory tests that, in the opinion 
of the Investigator, precludes participation in the study. The following abnormalities will 
specifically be considered exclusionary: 
a. Bilirubin >upper limit of normal (ULN) and/or any known condition that results in 
abnormal bilirubin elevations or fluctuations (eg, Gilbert’s, Dubin-Johnson, Rotor 
syndrome) 
b. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5× ULN 
12. Other co-morbidities that would introduce additional risk factors or interfere with study 
procedures based on clinically significant physical examination, vital sign, standard 
12-lead ECG, chemistry, hematology, urinalysis, or coagulation results at Screening as 
deemed by the Investigator  
13. Positive result for human immunodeficiency virus (HIV) or presence of actively 
replicating viral hepatitis due to hepatitis B virus (HBV) or hepatitis C virus (HCV) 
infection at Screening 
14. Significant history of abuse of drugs, solvents, or alcohol within the past year  
15. Participation in any clinical study with an investigational or approved drug/device within 
30 days or 5 half-lives (whichever is longer) before Day 1 or is planning to participate in 
another clinical study while enrolled in this study 


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16. History of known or suspected hypersensitivity to any component of study drug  
17. Female who is pregnant, nursing, or intends to become pregnant during the study 
18. Had a major surgery within 8 weeks prior to Day 1 or has a major surgery planned during 
the study  
19. Is directly affiliated with the study at the clinical site or is an immediate family member 
(spouse, parent, child, or sibling; biological or legally adopted) of personnel directly 
affiliated with the study at the clinical site  
20. Is employed by Escient Pharmaceuticals, Inc., (that is an employee, temporary contract 
worker, or designee responsible for the conduct of the study) or is an immediate family 
member of an employee of Escient Pharmaceuticals, Inc. 
21. Subject is, in the opinion of the Investigator, not suitable to participate in the study 
8.3. 
Study Restrictions 
Unless stated otherwise, subjects must adhere to the following restrictions from Screening until 
the end of the study unless subject safety is compromised: 
• On days of study visits, do not apply topical emollients prior to attending and 
completing each visit. 
• Do not take bleach baths. 
• Do not use any drugs of abuse (cannabinoids [eg, oil, recreation smoking] are not 
restricted). 
• Do not use any investigational drugs/devices. 
• Maintain current dose and regimen of all prescribed medication, unless changed in 
consultation with the Medical Monitor. 
• Do not start new medications, including prescription medications and antihistamines, 
during the study unless deemed necessary by a healthcare provider. 
• 
8.4. 
Concomitant Medications 
Subjects are to follow the medication restrictions outlined in the inclusion and exclusion criteria 
(Section 8.1 and Section 8.2) and subject restrictions (Section 8.3) during the study. 
The Investigator should contact the Medical Monitor with any questions about concomitant 
medication use or timing of administration. In instances where a medication is initiated prior to 
discussion with the Medical Monitor, the Investigator must notify the Medical Monitor as soon 
as he/she is aware of the use of the new medication to discuss the subject’s concomitant 
treatment and any impact to participation in the study.  


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All medications taken within 30 days before Screening and details of concomitant medications 
from Screening through the end of study participation should be recorded. In addition, all 
medications taken to treat AD beginning from the date of diagnosis should also be recorded. 
8.4.1. 
Background Therapy 
Subjects are to use a protocol-permitted, non-urea-containing emollient on lesional and 
nonlesional skin daily for at least 1 week before Day 1 and agree to continue using that same 
emollient daily at the same frequency (ideally once or twice daily) throughout the study. Subjects 
will record emollient use in a daily diary throughout the study. Every effort should be made to 
keep the same emollient throughout the study for the same body region.  
Subjects will delay emollient use on the days of study visits until after study procedures are 
completed.  
8.4.2. 
Rescue Medications 
New concomitant medications and procedures for treatment of AD are prohibited during the 
study. If a patient requires treatment with a new medication or procedure due to intolerable AD 
symptoms, study drug should be discontinued. Whenever possible, subjects should remain in the 
study and complete the remaining study visits and assessments even when study drug has been 
discontinued. 
8.5. 
Removal of Subjects from Therapy or Assessment 
If a subject discontinues study drug and/or is withdrawn from the study, the reason will be 
recorded on the electronic case report form (eCRF) page and the Sponsor will be notified within 
24 to 48 hours. 
8.5.1. 
Discontinuation of Study Drug 
Study drug may be discontinued in the following instances: 
• AE 
• Rescue medication use 
• Withdrawal of consent 
• Lost to follow-up 
• Protocol deviation 
• Investigator decision 


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• Sponsor decision 
• Pregnancy during the study (Section 11.2.3) 
• Other 
If a subject experiences a TEAE that is Common Terminology Criteria for Adverse Events 
(CTCAE) Grade 2 or higher in the Cardiac Disorders System Organ Class (SOC), Grade 2 or 
higher in CTCAE terms of Bone marrow hypocellular, Lymphocyte count decreased, 
Lymphocyte count increased, or Myelodysplastic syndrome, or Grade 3 or higher in other SOCs, 
the study drug must be discontinued. AE grading for severity using CTCAE criteria is described 
in Section 11.1.2 and determination of AE causality is described in Section 11.1.3.  
For subjects who terminate treatment with study drug early, regardless of the reason, every effort 
will be made to complete the early treatment termination evaluations as soon as possible after the 
last dose of study drug, ideally within 2 days after the last dose of study drug. 
Whenever possible, subjects should remain in the study and complete the remaining study visits 
and assessments even when study drug has been discontinued. Subjects who discontinue study 
drug for any reason and continue with the study visits as planned through Visit 4 (Week 6) 
(participating only in PD and safety, but not PK measures) will participate in the Follow-Up 
Visit if the last dose of study drug was administered less than 4 weeks before Visit 4 (Week 6) to 
ensure that at least 4 weeks of follow-up data are collected for all randomized subjects. 
If a subject discontinues study drug and chooses not to complete all of the remaining study visits, 
the subject should have the Early Treatment Termination Visit conducted as soon as possible 
after the last dose of study drug, ideally within 2 days after the last dose of study drug, and a 
Follow-Up Visit approximately 4 weeks (±3 days) after the last dose of study drug if at least 
4 weeks of follow-up data have not already been collected. If a subject fails to attend the 
Follow-Up Visit and has not withdrawn consent, all reasonable efforts will be made to contact 
the subject to ensure that he/she is in satisfactory health. All contacts and contact attempts must 
be documented in the subject’s medical record. 
8.5.2. 
Discontinuation from the Study 
Subjects may discontinue from the study at any time for any of the following reasons: 
• Death 
• Withdrawal of consent 
• Lost to follow-up 
• Termination of the study by the Sponsor or at the request of a regulatory agency or an 
IRB or IEC (Section 7.6) 
• Other 
A subject may elect to discontinue study participation at any time for any reason without 
prejudice to their future medical care by the physician or at the institution. If a subject withdraws 
consent, no further evaluation should be performed, and no additional data should be collected. 
The Sponsor may retain and continue to use any data collected before such withdrawal of 


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consent. The Investigator should make a reasonable attempt to document the specific reason why 
consent was withdrawn.  
9. 
TREATMENT OF SUBJECTS 
9.1. 
Treatment Assignment 
Approximately 30 subjects with AD will be randomized in a 2:1 ratio to receive either a 150 mg 
dose of EP262 or placebo PO, QD during the 6-week Double-Blind Treatment Period. 
9.2. 
Treatment Compliance 
The Investigator should assess the subject’s compliance with dosing of study drug by counting 
returned study drug capsules and reviewing the subject’s dosing diary as indicated in the 
Schedule of Assessments (Appendix A).  
If the Investigator has concerns about a subject’s dosing compliance, the Investigator should 
discuss this with the subject, assess the reasons for noncompliance and the likelihood that the 
subject will remain noncompliant, and notify the Sponsor accordingly. 
9.3. 
Randomization and Blinding 
9.3.1. 
Randomization 
Subjects will be randomized in a 2:1 ratio to receive either a 150 mg dose of EP262 or placebo 
PO, QD for 6 weeks during the Double-Blind Treatment Period beginning at Visit 2 (Day 1). 
Randomization will be conducted centrally via an IWRS. The master randomization list will be 
kept secured until the study blind is broken at the end of study. 
Subjects who withdraw for any reason without completing all screening evaluations successfully 
will be considered “screening failures”. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects, to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements, and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAEs. 
9.3.2. 
Blinding 
The Sponsor, Medical Monitor, Contract Research Organization (CRO) staff, Investigators, site 
staff, and subjects will be blinded to subject’s assigned treatment until the database is locked 
except for CRO or vendor staff involved in the analysis of PK samples. Procedures for 
emergency unblinding and unblinding for regulatory reporting are described in Section 9.3.2.1 
and Section 9.3.2.2, respectively. 
9.3.2.1. 
Emergency Unblinding 
If an emergency unblinding during the Double-Blind Treatment Period is required, the subject’s 
treatment assignment may be unblinded through IWRS by the Investigator. If a treatment 
assignment is unblinded, the subject will be discontinued from randomized treatment. 


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Blinding codes should only be broken in emergency situations for reasons of subject safety and 
when knowledge of the treatment assignment will impact the clinical management of the subject. 
Every reasonable attempt should be made to complete the post-treatment evaluation procedures 
prior to unblinding as knowledge of the treatment arm could influence subject assessment.  
In all emergency cases, the reasons and rationale for unblinding will be documented in writing 
and maintained in the study file. 
9.3.2.2. 
Unblinding for Regulatory Reporting 
Access to randomization codes and corresponding treatment assignment will be made available 
through the IWRS system to the appropriate individual(s) responsible for unblinding suspected 
unexpected serious adverse reactions for reporting to the Regulatory Authorities. 
9.4. 
Study Visits 
Subjects should fast for at least 8 hours before study visits that require a blood sample for 
assessment of clinical chemistry. Water is acceptable in the morning of clinic visits to ensure the 
subject is hydrated for laboratory sample collection. Subjects should fast at least 4 hours before 
administration of each dose of study drug and refrain from eating for at least 2 hours postdose. 
Each dose of study drug is to be taken with approximately 240 mL (8 fluid ounces) of water on 
an empty stomach. 
Study procedures are listed for each visit in the following sections and summarized in the 
Schedule of Assessments (Appendix A). Further details regarding safety, PD, baseline 
characterization, and PK assessments are located in Sections 11, 12, 13, and 14, respectively.  
9.4.1. 
Screening Period 
9.4.1.1. 
Visit 1 (Day -30 to Day -7 [inclusive]) 
During the Screening Period, subjects will undergo assessments to determine their study 
eligibility. Subjects will be screened and should meet all inclusion criteria and none of the 
exclusion criteria to be enrolled in the study. Any questions regarding eligibility may be 
discussed with the Medical Monitor. 
The following assessments may be conducted over more than 1 day but must be completed 
between Day -30 and Day -7 (inclusive): 
• Completion of informed consent before performance of any study procedures or 
assessments 
• Medical history, including AD disease history  
• Height  
• Body weight  
• Vital signs 
• Physical examination 
• Standard 12-lead ECG 


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• Assessment of baseline concomitant medications, including all medications taken to 
treat AD beginning from the date of diagnosis and all other medications taken within 
30 days before Screening  
• AE assessment 
• 
 
• Eligibility check  
• Blood and/or urine sample collection for screening and safety laboratory assessments 
• Lesional skin swab 
• Electronic device/app training  
• 
  
Subjects will be instructed to complete the
 
 
  
Subjects will also be instructed to record emollient use in a daily diary throughout the study. 
Screening results will be reviewed by the Investigator to determine the subject’s eligibility. 
Subjects who have an exclusionary result during the Screening Period (between Visit 1 and 
Visit 2) may have that assessment repeated once at the discretion of the Investigator within the 
screening window and be enrolled if a repeat assessment is within the indicated range as 
specified in Section 8 for participating in the study. Subjects who are confirmed to be eligible 
will be asked to return to the site for Visit 2 (Day 1) to be enrolled and randomized into the 
study.  
9.4.2. 
Double-Blind Treatment Period 
9.4.2.1. 
Visit 2 (Day 1) – Enrollment and Randomization 
Subjects who continue to meet study eligibility requirements will be enrolled and randomized 
during Visit 2 (Day 1).  
The following assessments will be performed during Visit 2 (Day 1): 
• 
  
• 
 
 
• Vital signs 
• Standard 12-lead ECG 
• Concomitant medication usage assessment 
• AE assessment 


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• 
 
 
• Eligibility check 
• Photographs of AD lesions and sites for skin swabs, skin tape strips application, and 
biopsies 
• Blood and urine sample collection for PD, safety, PK, and/or baseline 
characterization laboratory assessments  
• Lesional skin swab 
• Skin tape strips of lesional and nonlesional skin 
• Skin punch biopsy of lesional and nonlesional skin 
• Randomization to 150 mg EP262 or placebo in a 2:1 ratio via IWRS  
• Dispense study drug 
• Upon completion of the assessments listed above, study drug is to be administered PO 
as intact capsules (swallowed whole, not split, opened, or chewed) and taken with 
approximately 240 mL (8 fluid ounces) of water on an empty stomach 
Subjects will be instructed to record self-administration of study drug daily in a dosing diary 
throughout the Double-Blind Treatment Period. 
9.4.2.2. 
Visit 3 (Week 3) 
The following assessments will be performed during Visit 3 (Week 3): 
• 
  
• 
 
 
• Collect study drug  
• Assess study drug accountability and compliance  
• Vital signs 
• Abbreviated, symptom directed physical examination 
• Concomitant medication usage assessment 
• AE assessment 
• 
 
• Photographs of AD lesions and sites for skin swabs and skin tape strips application 
• Blood and urine sample collection for PD, safety, and/or PK assessments  
• Lesional skin swab 
• Skin tape strips of lesional skin 


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• Dispense study drug 
• Upon completion of the assessments listed above, study drug is to be administered PO 
as intact capsules (swallowed whole, not split, opened, or chewed) and taken with 
approximately 240 mL (8 fluid ounces) of water on an empty stomach 
9.4.2.3. 
Visit 4 (Week 6) 
The following assessments will be performed during Visit 4 (Week 6): 
• 
  
• 
 
 
• Collect study drug  
• Assess study drug accountability and compliance  
• Body weight  
• Vital signs 
• Physical examination 
• Standard 12-lead ECG 
• Concomitant medication usage assessment 
• AE assessment 
• 
 
• Photographs of AD lesions and sites for skin swabs, skin tape strips application, and 
biopsy 
• Blood and urine sample collection for PD, safety, and/or PK assessments  
• Lesional skin swab 
• Skin tape strips of lesional skin 
• Skin punch biopsy of lesional skin  
9.4.3. 
Follow-Up Period 
9.4.3.1. 
Visit 5 (Week 10)  
The following assessments will be performed during the Follow-Up Visit, approximately 
4 weeks after the last dose of study drug: 
• 
  
• 
 
 
• Body weight  


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• Vital signs 
• Abbreviated, symptom directed physical examination 
• Standard 12-lead ECG 
• Concomitant medication usage assessment 
• AE assessment 
• 
 
• Photographs of AD lesions  
• Blood and urine sample collection for PD, safety, and/or PK assessments  
9.4.4. 
Early Treatment Termination Visit  
Subjects who discontinue from treatment early should have the Early Treatment Termination 
Visit conducted as soon as possible after the last dose of study drug, ideally within 2 days after 
the last dose of study drug. The following assessments will be performed during the Early 
Treatment Termination Visit: 
• 
  
• 
 
  
• Collect study drug  
• Assess study drug accountability and compliance  
• Body weight  
• Vital signs 
• Abbreviated, symptom directed physical examination 
• Standard 12-lead ECG 
• Concomitant medication usage assessment 
• AE assessment 
• 
 
• Photographs of AD lesions 
• Blood and urine sample collection for PD, safety, and/or PK assessments  
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
10.1. 
Study Drug 
Capsules containing 75 mg of EP262 or placebo will be supplied in bottles in a manner to ensure 
the study blind. Each subject will take 2 capsules per dose, with subjects randomized to EP262 
receiving a total of 150 mg per day. 


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10.2. 
Study Drug Packaging and Labeling 
Study drug will be packaged into bottles with child-resistant caps, induction sealed, labeled with 
a unique number, and supplied to clinical sites in a blinded manner. 
10.3. 
Study Drug Storage 
The study drug capsules should be stored at controlled room temperature, 15°C to 25°C (59°F to 
77°F), with excursions up to 30°C (86°F). 
10.4. 
Study Drug Administration 
Each study drug dose is to be administered PO as intact capsules (swallowed whole, not split, 
opened, or chewed) and taken with approximately 240 mL (8 fluid ounces) of water on an empty 
stomach. Subjects will be instructed to take the study drug at approximately the same time of the 
day after a fast of at least 4 hours. Subjects should refrain from eating for at least 2 hours 
postdose. On the days of clinic visits, the time of study drug administration may differ depending 
on the scheduled visit time. The first dose of study drug will be administered at the clinical site 
on Visit 2 (Day 1) after all baseline study procedures are completed. 
10.4.1. 
Instructions for Missed Dose(s) 
Subjects should be instructed that if they forget to take a dose, they can take the dose within 
8 hours of the normal dosing time; otherwise, they should take their next dose at the regular time 
on the following day. If the subject vomits the capsules, he/she should be instructed not to take 
additional capsules on the same day but to take the next dose at the regular time on the following 
day. Subjects should be instructed to contact the Investigator if they miss 2 or more consecutive 
doses. 
10.5. 
Study Drug Dispensing and Accountability 
Subjects will record self-administration of study drug daily in a dosing diary, which will be 
reviewed by clinical site staff at each clinic visit during the Double-Blind Treatment Period 
following Visit 2. 
Subjects should be instructed to retain the study drug, including the study drug bottle, even if 
empty, and to return it and any remaining study drug to the clinical site during their next visit. 
The site staff should perform study drug accountability and, if applicable, follow-up with the 
subject to retrieve any remaining study drug that has not been returned. 
10.6. 
Study Drug Handling and Disposal 
Study drug will be sent to the clinical site under appropriate storage conditions. Upon receipt of 
study drug, site staff are to open the shipment, and verify that the amount and identity of the 
contents match that stated in the enclosed shipping form. The Sponsor (or designee) is to be 
notified immediately about any irregularities, discrepancies, or damage. 
Study drug will be provided for use only in this study and is not to be used for any other purpose. 
The site staff will maintain a full record of study drug accountability as described in 
Section 10.5.  


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Upon completion of the study, used and unused study drug and study drug bottles are to be 
returned to the Sponsor (or designee) or, if prior Sponsor approval is obtained, disposed of in 
accordance with applicable site procedures. Site staff must maintain documentation of any 
missing or unreturned study drug. The final disposition of all study drug received at the site is to 
be documented. 
10.7. 
Product Quality Complaints 
A product quality complaint (PQC) is defined as any suspicion of a product defect or deficiency 
related to manufacturing, labeling, or packaging (ie, any dissatisfaction relative to the identity, 
quality, durability, reliability, safety, effectiveness, or performance of a product, including its 
labeling or package integrity). A PQC may have an impact on the safety and efficacy of the 
product. Timely, accurate, and complete reporting and analysis of PQC information from studies 
are crucial for the protection of subjects. 
All initial PQCs must be reported to the Sponsor or CRO by clinical-site personnel within 
24 hours after being made aware of the potential defect. Whenever possible, the associated 
product should be maintained in accordance with the label instructions pending further guidance 
from the Sponsor.  
11. 
SAFETY ASSESSMENTS 
Safety evaluations, including AEs, concomitant medications, medical history, vital signs, 
physical examinations, standard 12-lead ECGs, and laboratory evaluations of safety will be 
performed as indicated in the Schedule of Assessments (Appendix A). 
11.1. 
Adverse Events 
11.1.1. 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically 
significant abnormal laboratory finding), symptom, or disease temporally associated with the use 
of a medicinal (investigational) product. 
Medical conditions present at baseline that worsen in severity or frequency after exposure to 
study drug are considered TEAEs. A TEAE is any condition that was not present prior to 
treatment with the study drug 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). Planned hospital admissions or surgical procedures for an 
illness or a disease that existed before administration of study drug, and for which the condition 
has not worsened since starting study drug, are not to be considered TEAEs/treatment-emergent 
SAEs. Events with emergency room visits that are less than 24 hours will also not be considered 
SAEs unless they meet one of the criteria listed in Section 11.2.1. 


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Clinically significant abnormal laboratory tests, 12-lead ECG assessments, or vital sign results 
may constitute an AE if they meet one of the criteria listed in Section 11.1.4.1. However, 
whenever possible, the underlying diagnosis should be listed in lieu of associated abnormal 
results. Abnormalities deemed not clinically significant by the Investigator should not be 
reported as AEs. 
11.1.2. 
Determining Severity of Adverse Events 
AEs must be graded for severity (ie, intensity) using CTCAE, version 5.0 (HHS 2017). A 
severity category of mild, moderate, severe, life-threatening, or death, as defined in Appendix B, 
must be entered on the AE eCRF. The criteria below are to be used for determining the severity 
of AEs where there is no actual CTCAE term for the specific reported AE found in the CTCAE, 
version 5.0 guideline (Appendix B). It should be noted that the term “severe” used to grade 
intensity is not synonymous with the term “serious”. The assessment of severity is made 
regardless of the relationship to study drug or of the seriousness of the AE. When reporting AEs, 
reference should be made to the CTCAE manual for guidance on appropriate grading.  
Grade 1: 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
Grade 2: 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
(eg, preparing meals, shopping for groceries or clothes, using the 
telephone, managing money). 
Grade 3: 
Severe or medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, 
limiting selfcare activities of daily life (eg, bathing, dressing and 
undressing, feeding self, using the toilet, taking medications, not 
bedridden). 
Grade 4: 
Life-threatening consequences; urgent intervention indicated. 
Grade 5: 
Death related to AE. 
11.1.3. 
Determining Causality of Adverse Events 
Causality refers to the relationship of the event to the study drug (EP262 or placebo). The 
Investigator will assess the causality of the event according to the following criteria: 
• Not related – A reaction for which sufficient data exist to indicate that the etiology is 
unrelated to the study drug. 
• Related – A reaction that follows a reasonable temporal sequence from 
administration of study drug; that follows a known or expected response pattern to the 
study drug, which may or may not reasonably have been produced by a number of 
other factors including underlying disease, complications, concomitant drugs, or 
concurrent treatments; and/or that could not be reasonably explained by other factors 
such as underlying disease, complications, concomitant drugs, or concurrent 
treatments; and/or disappears or decreases on cessation or reduction in study drug 
dose; and/or reappears or worsens when the study drug is administered. 


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11.1.4. 
Recording Adverse Events 
All AEs must be recorded in the source documents and in the eCRFs provided by the Sponsor 
from the signing of the Informed Consent Form (ICF) until the end of study participation. AEs 
will be assessed for likelihood of causal relationship to the study drug (EP262 or placebo) and 
severity.  
The new onset of signs, symptoms, or other findings that occur before signing of the ICF will be 
captured as medical history (Section 11.3).  
11.1.4.1. Special Instructions for Recording Adverse Events in the eCRF 
Diagnosis versus Signs and Symptoms 
If a diagnosis is known at the time of reporting, this should be recorded in the eCRF rather than 
the individual signs and symptoms (eg, record only hepatitis rather than elevated transaminases, 
bilirubin, and jaundice). However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded as an SAE or AE on the eCRF. If a diagnosis is subsequently 
established, it should be reported as follow-up and should replace the individual signs and/or 
symptoms as the event term on the eCRF, unless the signs/symptoms are clinically significant. 
Adverse Events Occurring Secondary to Other Events 
In general, AEs occurring secondary to other events (eg, clinical sequelae or a cascade of events) 
should be identified by their primary cause. For example, if severe vomiting is known to result in 
dehydration, it is sufficient to record only vomiting as an SAE or AE on the eCRF. However, 
medically significant AEs occurring secondary to an initiating event that are separated in time 
should be recorded as independent events on the eCRF. For example, if severe vomiting leads to 
acute renal failure, both events should be recorded on the eCRF. 
Persistent or Recurrent Adverse Events 
A persistent AE is one that extends continuously, without resolution, between subject evaluation 
timepoints. Such events should only be recorded once on the eCRF. If a persistent AE becomes 
more severe or lessens in severity, it should be recorded as a new AE on the eCRF.  
A recurrent AE is one that occurs and resolves between subject evaluation timepoints, and 
subsequently recurs. Each reoccurrence of an AE should be recorded on the eCRF. 
Abnormal Laboratory Values or Vital Signs 
Protocol defined laboratory values and vital signs will be reported as AEs if the abnormal 
laboratory or vital sign result: 
• Requires an adjustment in the study drug(s) or discontinuation of treatment;  
• Requires additional testing, excluding repeat testing of the lab in question, or surgical 
intervention;  
• Is associated with accompanying signs/symptoms that are not considered part of a 
preexisting diagnosis or syndrome; or 
• Is considered clinically significant by the Investigator 


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If an abnormal laboratory value or vital sign is the result of an evaluation of clinical signs, 
symptoms, or suspected diagnosis during the conduct of the study, the signs/symptoms or 
diagnosis should be reported as an AE (or if appropriate, an SAE) only if clinically significant, 
and the associated laboratory value or vital sign should be considered additional information that 
must be collected on the relevant eCRF.  
11.2. 
Serious Adverse Events  
11.2.1. 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence, that at any dose:  
• Results in death; 
• Is life-threatening, ie, the subject is, in the opinion of the Investigator, at immediate 
risk of death from the event as it occurred, (it does not include an event that, had it 
occurred in a more severe form, might have caused death);  
• Requires hospital admission or prolongs hospitalization. Planned hospital admissions 
or surgical procedures for an illness or a disease that existed before administration of 
study drug, and for which the condition has not worsened since starting study drug, 
are not to be considered SAEs. Emergency room visits that are less than 24 hours will 
also not be considered SAEs unless any of the other serious criteria is fulfilled; 
• Results in persistent or significant disability or incapacity; 
• Is a congenital anomaly/birth defect; or 
• Is a medically significant event that, based on appropriate medical judgment, may 
jeopardize the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed above. 
Note: A distinction should be drawn between SAEs and severe AEs. Severity is a measure of the 
intensity of an AE, while the criteria for seriousness are indications of adverse subject outcomes 
for regulatory reporting purposes. A severe AE is not necessarily considered an SAE. For 
example, a headache that persists for several hours may be considered a severe AE but not an 
SAE. Conversely, a wound infection that may be considered minor could be an SAE if it 
prolonged hospitalization. 
11.2.2. 
Reporting Serious Adverse Events 
The Investigator and the Sponsor will monitor safety for this study. A Serious Adverse Event 
Report (SAER) Form is to be completed for each SAE occurring after signing of the ICF until 
30 days after the last dose of study drug, regardless of causality.  
All SAE reports must be reported within 24 hours of the Investigator’s knowledge of the 
event to 
. If requested by the Sponsor, any supporting 
documentation (eg, medical records) sent to 
 with the 
SAER Form must have subject identifying information (eg, subject names, subject addresses, 
medical records number) redacted by the site. Follow-up information to all SAEs should be 
submitted to the Sponsor, or designee, in the same timeframe as initial reports. 


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All SAEs will be followed until resolution or medical stabilization (in cases where resolution 
would not be expected). 
In accordance with applicable regulations and local laws, the Sponsor or designee will report all 
serious and unexpected AEs assessed as related to study drug by the Investigator and/or Sponsor, 
to the regulatory authorities within the required timeframe. The Investigator will be responsible 
for reporting this safety information to his or her IRB/IEC. 
If the Investigator becomes aware of an SAE any time after study completion and determines it is 
related to the study drug, the SAE must be reported to the Sponsor or designee within 24 hours 
of the Investigator’s knowledge of the SAE. 
11.2.3. 
Pregnancy 
Pregnancy in and of itself is not an AE, although pregnancies occurring in subjects or partners of 
male subjects are considered immediately reportable events. If a pregnancy occurs in a subject, 
study drug must be discontinued immediately. The pregnancy must be reported to 
 
Drug Safety via email at 
 within 24 hours of the 
Investigator’s knowledge of the pregnancy using the Pregnancy Reporting Form.  
The Investigator will follow the pregnant woman until completion of the pregnancy, and must 
notify the Sponsor, or designee, of the outcome within 24 hours of the Investigator’s knowledge 
of the pregnancy outcome. The Investigator will provide this information on the Pregnancy 
Reporting Form. This notification includes pregnancies resulting in live, “normal” births. 
If the pregnant subject experiences an SAE during pregnancy, or the outcome of the pregnancy 
meets the criteria for immediate classification as an SAE (ie, spontaneous abortion [any 
congenital anomaly detected in an aborted fetus is to be documented], stillbirth, neonatal death, 
or congenital anomaly), the Investigator should follow the procedures for reporting SAEs 
(ie, report the event to the Sponsor via email at 
 
within 24 hours of the Investigator’s knowledge of the event). 
All neonatal deaths and congenital anomalies that occur within 30 days of birth (regardless of 
causality) should be reported as SAEs to the Sponsor or designee. In addition, any infant death or 
congenital anomaly occurring after study completion that the Investigator suspects is related to 
the in-utero exposure to the study drug should also be reported to the Sponsor or designee. 
11.3. 
Medical History 
The Investigator or designee will collect and review the subject’s medical history, including AD 
disease history, to evaluate the subject’s eligibility for study participation. The new onset of 
signs, symptoms, or other findings that occur from before signing of the ICF will be captured as 
medical history.  
11.4. 
Vital Signs 
Vital signs, including sitting systolic and diastolic blood pressure, pulse rate, body temperature, 
and respiratory rate, will be measured predose (as applicable) after at least 5 minutes of rest. 
Vital signs are to be performed predose if the dose is administered at the site. 


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11.5. 
Body Weight and Height 
Body weight should be measured with no shoes and heavy clothing (outdoor clothing such as 
coats) on and using a calibrated scale throughout the study. Height should be measured using a 
stadiometer with no shoes. 
11.6. 
Physical Examinations 
Physical examinations will include but are not limited to an assessment of general appearance, 
skin, HEENT (head, eyes, ears, nose, throat), musculoskeletal, thyroid/endocrine, cardiovascular, 
chest/lung, neurologic, abdomen, and extremities/general body systems.  
Abbreviated, symptom directed physical examinations to assess clinically significant changes 
from Screening or any new signs or symptoms will be conducted at Visit 3 (Week 3), Visit 5 
(Week 10), and the Early Treatment Termination Visit, and may be conducted at other visits as 
determined by the Investigator based on subject complaint. 
Clinically significant abnormalities from before signing of the ICF will be recorded as medical 
history, and clinically significant changes after signing the ICF will be recorded as AEs. 
11.7. 
Standard 12-Lead Electrocardiograms  
Twelve-lead ECGs are to be performed predose (as applicable) with subjects in a supine position 
after at least 5 minutes of rest. An ECG is to be performed predose if the dose is administered at 
the site. 
11.8. 
Laboratory Evaluations of Safety 
Samples for the following laboratory tests should be collected after an overnight fast (at least 
8 hours): 
• Chemistry: sodium, albumin, alkaline phosphatase (ALP), bicarbonate, calcium, 
corrected calcium, chloride, bilirubin (total, indirect, and direct), AST, ALT, blood 
urea nitrogen, urea, creatinine, glucose, magnesium, phosphorus, potassium, creatine 
phosphokinase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, 
low-density lipoprotein cholesterol, lactate dehydrogenase, gamma-
glutamyltransferase, and total protein 
• Hematology: hemoglobin, hematocrit, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration, mean corpuscular volume, white blood cell 
count (total and differential), red blood cell count, platelet count, and platelet volume 
• Urinalysis: leukocyte esterase, nitrites, pH, protein, specific gravity, glucose, occult 
blood, ketones, bilirubin, and urobilinogen; microscopic analysis is to be performed 
only if protein, leukocyte esterase, blood or nitrite is positive 
• Coagulation: activated partial thromboplastin time, international normalized ratio 
(INR), and prothrombin time 
• Pregnancy testing: required for all females; serum test at Screening (Visit 1) and urine 
test for all other visits where pregnancy testing is required  


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The urine pregnancy test for female subjects will be conducted locally; all other planned 
laboratory evaluations of safety will be conducted at a central laboratory. Details for sample 
collection, processing, storage, and shipment will be provided in the Laboratory Manual. 
11.9. 
Other Laboratory Evaluations 
Samples for the following laboratory tests will be collected:  
• Serology: HIV I/II, HBV (hepatitis B surface antigen), HCV 
These planned laboratory evaluations will be conducted at a central laboratory. See the 
Laboratory Manual for additional details. 
11.10. 
Subject Safety Guidelines  
11.10.1. 
Potential Side Effects 
Refer to Section 5.4.2 and the Investigator’s Brochure for additional EP262 information 
regarding potential side effects. 
11.10.2. 
Overdose 
No specific information is available on the treatment of overdose of EP262. Additionally, there is 
no specific antidote to EP262. In a case of overdose, appropriate supportive measures should be 
employed and the case documented as a protocol deviation (Section 17.1). An overdose does not 
constitute an AE; however, the subject should be closely monitored for any potential AEs. 
The overdose must be reported to 
 Drug Safety via email at 
 within 24 hours of the Investigator’s knowledge of the 
overdose using the Overdose Reporting Form. 
11.10.3. 
Management of Liver Test Abnormalities 
Subjects with an increase in ALT or AST to >3× ULN OR total bilirubin >2× ULN should be 
followed by repeat testing within 48 to 72 hours of the initial serum chemistry results, if possible, 
to monitor for suspected drug-induced liver injury. Test results from local laboratories and the 
associated normal ranges are to be captured in the database. In conjunction with this, a physical 
examination should be performed and AE information should be collected. If symptoms persist 
or repeat testing shows ALT or AST >3× ULN or total bilirubin >2× ULN, subjects should be 
closely monitored as defined below to determine whether the abnormalities are improving or 
worsening:  
• Repeating liver enzyme and serum bilirubin tests 2 or 3 times weekly. Frequency 
of retesting can decrease to once a week or less if abnormalities stabilize or study 
drug has been discontinued and the subject is asymptomatic.  
• Obtaining a more detailed history of symptoms and prior or concurrent diseases.  
• Obtaining a history of concomitant drug use (including nonprescription 
medications and herbal and dietary supplement preparations), alcohol use, 
recreational drug use, and special diets.  


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• Ruling out acute viral hepatitis types A, B, C, D, and E; autoimmune or alcoholic 
hepatitis; hypoxic/ischemic hepatopathy; and biliary tract disease.  
• Obtaining a history of exposure to environmental chemical agents.  
• Obtaining additional tests to evaluate liver function, as appropriate (eg, INR, 
direct bilirubin). 
If close observation is not possible, study drug should be interrupted until further investigation 
can be performed. 
Rechallenge may be considered if an alternative cause for the abnormal liver tests (ALT, AST, 
total bilirubin) is identified and the laboratory abnormalities resolve to normal or baseline values. 
The Investigator and Sponsor’s designated Medical Monitor must discuss and agree with any 
decision to rechallenge. Rechallenge should not occur when the etiology of the liver test 
abnormalities is considered possibly drug-induced. 
Discontinuation of treatment should be considered if the following abnormality or group of 
abnormalities occur: 
• ALT or AST >8× ULN  
• ALT or AST >5× ULN for more than 2 weeks  
• ALT or AST >3× ULN AND total bilirubin >2× ULN OR INR >1.5  
• ALT or AST >3× ULN with the appearance of new onset fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)  
12. 
PHARMACODYNAMIC ASSESSMENTS 
Examples of the patient-reported assessments are provided in the appendices but are not to be 
distributed to subjects for completion. Subjects will be trained on completion of all patient-
reported assessments using a study-issued electronic device or application (app). 
All subjects who were given a study-issued device, including those who fail Screening, will be 
required to return it to the site once their participation in the study is complete. 
12.1. 
Skin Swabs 
A cotton swab will be passed along the lesional skin of the area of worst involvement at 
Screening. The skin swab will be placed in aerobic culture and analyzed for the presence of 
S. aureus. At 
 skin swabs will be collected from 


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the same lesional site, even if the lesion has cleared, for assessment of 
. 
Skin swabs are to be collected before skin tape strips application and biopsies when performed 
on the same day. 
12.2. 
Skin Tape Strips 
Commercially available adhesive sheets will be applied on the surface of the skin at predefined 
areas. This procedure will be repeated up to 20 times sequentially on the same area to collect 
samples from the stratum corneum for proteomic assessment. Skin tape strips will be applied to 
AD lesional skin on Visits 2, 3, and 4 (Day 1, Week 3, and Week 6, same location, even if the 
lesion has cleared), and at a nonlesional site at Visit 2 (Day 1). 
12.3. 
Skin Punch Biopsies 
Two 4.0-mm skin biopsies will be collected on Visit 2 (Day 1), one from lesional skin and one 
from nonlesional skin in the vicinity of the lesional skin, and one 4.0-mm skin biopsy will be 
collected on Visit 4 (Week 6) from the same lesional skin, at least 1 cm away from the previous 
scar, even if the lesions have cleared. 
 
 The location of the 
biopsies will be 1 to 2 cm away from where the skin tape strips were applied, when both are to 
be performed on the same day. If it is not possible to collect the biopsy sample from the same 
lesion as the tape strips, it should be collected from a similar lesion in the same anatomical area.  
12.4. 
Disease Severity Scores 


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12.5. 
Pruritus 
12.6. 
Disease Control 
12.7. 
Quality of Life 


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12.9. 
Photographs of AD Area 
Representative photographs will be taken of the area of worst lesional involvement at Visit 2 
(Day 1) and of the same area at Visit 3 (Week 3), Visit 4 (Week 6), and Visit 5 (Follow-Up). 
Photographs will also be taken of areas selected for skin swabs, skin tape strips application, and 
biopsies before these procedures are conducted. 
13. 
BASELINE CHARACTERIZATION 
A blood sample will be collected at Visit 2 (Day 1) for measurement of HDM-specific IgE. 
Blood samples will also be taken at Visit 2 (Day 1) for genotyping to evaluate UGT1A1 and 
filaggrin polymorphisms to enable pharmacogenomic analyses. 
14. 
PHARMACOKINETICS ASSESSMENT 
Blood sampling will be collected predose (as applicable) at Visit 2 (Day 1), and each visit 
thereafter to analyze trough EP262 concentrations. The EP262 metabolite profile may also be 
analyzed from these trough samples. 
15. 
STATISTICS 
Data summaries will use descriptive statistics (n, mean, standard deviation, median, minimum, 
and maximum) for continuous variables and frequency and percentage for categorical and 
ordinal variables. Unless otherwise specified, endpoints will use the last pre-treatment value 
prior to the first dose of study drug as baseline. All data collected will be included in subject data 
listings. 
A formal Statistical Analysis Plan (SAP) will be prepared and finalized before database lock. 
Additional statistical analysis details will be included in the SAP. 


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15.1. 
Analysis Sets 
The following analysis sets will be considered: 
• Full Analysis Set: All subjects who are randomized and take at least 1 dose of 
randomized study drug will be included in the Full Analysis Set (FAS). Subjects in 
the FAS will be analyzed according to randomized treatment assignment. All PD 
analyses will be based on the FAS.  
• Per Protocol Set: The Per Protocol (PP) Set is a subset of the FAS containing 
subjects who meet study eligibility requirements and had no protocol deviations that 
might impact the assessment of PD measurements. Subjects will be analyzed 
according to randomized treatment assignment. The PP Set will be used for 
sensitivity analyses relating to PD. The type of protocol deviations governing 
exclusion from the PP Set will be determined prior to database lock and will be 
detailed in the SAP. 
• Safety Analysis Set: All subjects who are randomized and take at least 1 dose of 
randomized study drug will be included in the Safety Analysis Set. Safety analyses 
will be based upon treatment actually received. 
• PK Set: All subjects who receive at least 1 dose of EP262 and provide adequate 
blood samples for bioanalysis will be included in the PK Set.  
15.2. 
Sample Size Considerations 
No formal sample size calculation has been made. The sample size has been selected to provide 
adequate information on the safety, tolerability, PK, and PD of EP262 over 6 weeks. 
15.3. 
Subject Disposition 
Disposition of subjects will be summarized by treatment group and overall. Completion status 
and reasons for discontinuation will also be summarized. 
The number and percentage of subjects in each analysis set will be summarized. 
15.4. 
Demographics and Baseline Characteristics 
Demographic data and baseline characteristics for each analysis set will be summarized by 
treatment group and overall using descriptive statistics. 
15.5. 
Study Drug Usage and Compliance 
Compliance rate will be computed for each subject and will be summarized for the Safety 
Analysis Set using summary statistics by treatment group and overall. 
Duration of treatment will also be summarized. 
15.6. 
Safety Analysis 
The Safety Analysis Set will be used for the summaries of the safety data. Safety data will be 
summarized by treatment group and overall.  


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The safety and tolerability of EP262 will be assessed by comparing the frequency, causality, and 
severity of AEs as well as treatment discontinuations due to AEs. AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA) by SOC and Preferred Term. AEs that 
begin after the first administration of study drug, or existing AEs that worsen after the first dose 
of study drug, are considered treatment emergent. All AE summaries will include TEAEs, and all 
AEs will be presented in data listings. 
Concomitant medications will be coded using the World Health Organization (WHO) Drug 
Dictionary and summarized descriptively by Anatomic Therapeutic Chemistry (ATC) class using 
counts and percentages. Medications started prior to the first dose of study drug will be indicated 
in the data listings. Use of protocol-permitted emollient will also be summarized descriptively. 
Changes in vital signs, standard 12-lead ECGs, and laboratory evaluations will be summarized 
descriptively.  
15.7. 
Pharmacodynamic Analysis 
PD analyses will be based on the FAS. Select secondary and exploratory PD endpoint analyses 
may also be repeated in the PP Set, if sufficiently different to the FAS, as supportive analyses. 
PD analyses will compare placebo and EP262 descriptively. No formal statistical testing will be 
performed. For select PD endpoints, the 90% confidence interval and/or nominal p-values will be 
presented. 
For select endpoints, absolute, percent change, and/or fold-change from baseline will be 
summarized. Correlation analysis between responses in disease severity scores and changes in 
select PD parameters may be explored. Additional information will be provided in the SAP. 
15.8. 
Pharmacokinetic Analysis 
The PK Set will be used for the summaries of plasma concentrations of EP262. A descriptive 
summary of the observed plasma concentrations will be displayed by time. 
15.9. 
Subgroup Analyses 
Given the small sample size, no formal subgroup analyses are planned for this study.  
15.10. 
Multiple Comparison/Multiplicity 
No adjustment for multiplicity will be performed due to the hypothesis generating nature of this 
study.  
15.11. 
Planned Interim Analysis 
Given the hypothesis-generating nature of this study, an interim analysis may be conducted. The 
interim analysis would evaluate the effects of EP262 on select PD endpoints and safety. 
The decision to conduct an optional interim analysis and the timing of the analysis will be 
documented in the study files prior to conduct of the interim analysis. Additional details about 
the interim analysis, if applicable, will be provided in the SAP, which is to be finalized before 
the database lock and unblinding of the study data, as applicable. The SAP will be amended if 


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emerging data from the completed interim analysis leads to substantial change in the study 
protocol that has significant impact on the statistical analyses. 
16. 
QUALITY CONTROL AND DATA MANAGEMENT 
16.1. 
Data Quality Assurance 
The following measures will be implemented to ensure accuracy, consistency, completeness, and 
reliability of data: 
• Investigator discussions 
• Site initiation training 
• Early site visits following enrollment 
• Routine site management 
• Ongoing site communication and training 
• Periodic site monitoring  
• Review of the eCRF against source data for all subjects 
• Data management quality control (QC) checks 
• Statistical QC checks 
16.2. 
Data Management 
A database will be designed and built based on the final eCRFs. A Data Management Plan will 
be written specifying the procedures that will be used for medical coding, SAE reconciliation, 
QC, laboratory data, and data cleaning that will occur for the study. A Data Validation 
Specifications document will be written and edit checks will be programmed and validated.  
16.3. 
Monitoring 
Monitoring visits will be conducted by representatives of the Sponsor according to the 
International Council for Harmonisation (ICH) Guideline for GCP, and applicable regional 
regulations and guidelines.  
A monitor (or monitors) will review and verify protocol compliance with a focus on AE/SAE 
reporting, eCRF data, source documentation, ICFs, and any other study-related documentation, 
including review of site pharmacy procedures, drug accountability documentation, and drug 
storage facilities and records. 
Monitoring will be on an ongoing basis. Before database lock, 100% eCRF data verification will 
be performed against the source documents. The Investigator will agree to the monitor(s) making 
periodic site visits during the study. The monitor(s) and the site staff will agree upon the timing 
of these visits. 
Centralized monitoring, which consists of remote review of accumulating data from all sites, will 
be performed as detailed in the Centralized Monitoring Plan. 


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16.4. 
Confidentiality and Auditing 
The Investigator, the Sponsor, and the Sponsor’s representatives will preserve the confidentiality 
of all subjects participating in this study, in accordance with ICH GCP, local regulations, and 
institutional requirements. Only year of birth, age at Screening, and study subject number will be 
used to identify subjects on the eCRFs and other study-related documents submitted to the 
Sponsor (or designee). Documents that are not submitted to the Sponsor (eg, ICFs) should be 
kept in strict confidence by the investigative staff. 
In compliance with ICH GCP, it is required that the Investigator and institution permit 
authorized representatives of the Sponsor, the IRB/IEC, the US Food and Drug Administration 
(FDA), and other appropriate regulatory authority or health authority inspectors’ direct access to 
all study-related sites, source data, documents, and reports for verification of study records and 
data. Direct access is the permission to examine, analyze, verify, and reproduce any records and 
reports that are important to the evaluation of a clinical study. The Investigator is obligated to 
inform and obtain consent from the subject to permit these representatives to have access to their 
study-related records for this verification. Any party (eg, domestic and foreign regulatory 
authorities, Sponsors, auditors) with direct access should take all reasonable precautions within 
the constraints of the applicable regulatory requirement(s) to maintain the confidentiality of 
subjects.  
In case of data security breach, measures to mitigate possible adverse effects for subjects will be 
applied as per the CRO’s standard operating procedure (SOP). 
16.5. 
Case Report Forms 
eCRFs will be used for this study. Site personnel will receive training on eCRF completion. Each 
eCRF is to be reviewed and approved by the Investigator.  
During periodic monitoring visits, the eCRFs will be made available to the study monitor so that 
he or she may verify the data entries with the source documentation. 
16.6. 
Source Documents 
The Investigator will prepare and maintain adequate and accurate source documents (eg, medical 
records, 12-lead ECG results, raw data collection forms) to record all observations and other 
pertinent data for each subject enrolled into the study. The data recorded on the eCRFs will be 
derived from these source documents. The Investigator will ensure that data on the eCRFs and 
completed queries are accurate, consistent with source documentation, and submitted to the 
Sponsor in a timely manner. The Investigator will also ensure that all data on required study logs 
are accurate and kept up to date. 
16.7. 
Records Retention 
The Investigator must maintain essential study documents (protocol and amendments, completed 
eCRFs, source documentation, signed ICFs, relevant correspondence and approvals, and all other 
supporting documentation) until notified by the Sponsor. Subject identification codes (subject 
names and corresponding study numbers) will be retained for this same period and stored 
separately. Custody of the records may be transferred to another responsible party, acceptable to 
the Sponsor, which agrees to abide by the retention policies. Written notice of transfer must be 


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submitted to the Sponsor. The Investigator must contact the Sponsor before disposing of any 
study records. 
Records retention will follow the data protection requirements in each country. 
16.8. 
Informed Consent 
Written informed consent will be obtained from each subject before any study-related procedures 
are performed. The Investigator has an ethical and legal responsibility to ensure each subject 
being considered for inclusion in the study is given a full explanation of the study. The 
Investigator, or his/her designee, shall inform each subject, in writing, of all aspects pertaining to 
participation in the study, including (but not limited to) aims, methods, anticipated benefits, and 
potential risks. Subjects will have the opportunity to inquire about details of the study and to 
decide whether to participate. Subjects should understand that they are free to refuse to 
participate in, or to withdraw from, the study at any time without prejudice or loss of medical 
care to which they are otherwise entitled. Each subject must personally sign and date a study-
specific ICF to be a subject in the study. The ICF must be countersigned by the site Investigator 
(or designee) who conducted the informed consent discussion. This will be documented on a 
written ICF. Each ICF will include the elements required by US 21 Code of Federal Regulations 
(CFR) 50 and ICH E6, Section 4.8. The Investigator agrees to obtain approval from the Sponsor 
of any written informed consent for use in the study before submission to the IRB/IEC. 
Each subject who provides written informed consent for the study (by signing and dating the 
ICF), will be given a copy of the signed ICF. The original will be kept in the subject’s medical 
record or study chart as permitted by the institution. The Investigator will inform subjects of new 
information that may be relevant to the subjects’ willingness to continue participation in the 
study according to local ethics requirements. 
It is important to obtain complete follow-up for all subjects. Every attempt should be made to 
undertake all protocol-specified assessments and complete the eCRFs except for those subjects 
who specifically withdraw consent for release of such information. 
16.9. 
Ethical Conduct of the Study 
This study shall be conducted in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki and that are consistent with GCP, ICH guidelines, other applicable 
regulatory requirements (eg, local requirements), the study protocol, and where applicable, 
Sponsor and/or CRO SOPs. 
16.10. 
Institutional Review Board/Independent Ethics Committee 
The Investigator will not begin the study until the protocol and ICF have been approved by the 
appropriate independent IRB/IEC. Any amendments to the protocol must also be approved in 
writing by the Sponsor and IRB/IEC, before implementation by the Investigator, except where 
necessary to eliminate an immediate hazard to subjects. 
All IRB/IEC correspondence, including progress reports, will be retained on file at the site. 


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17. 
STUDY MANAGEMENT 
17.1. 
Protocol Deviations 
The Investigator is not permitted to deviate from the protocol in any major way without proper 
notification to the Sponsor (or designee). Only the Sponsor may revise the protocol. Any change 
in study conduct considered necessary by the Investigator will be made only after consultation 
with the Sponsor, who will then issue a formal protocol revision to implement the change and 
obtain regulatory and ethic approval. The only exception is when the Investigator considers a 
subject’s safety to be compromised if immediate action is not taken. 
In the event of an important deviation from the protocol, the Investigator or designee must 
contact the Sponsor or representative at the earliest possible time. This will allow an early joint 
decision regarding the subject’s continuation in the study.  
Examples of important deviations include: 
• Subject did not give appropriate informed consent 
• Inclusion or exclusion criteria not satisfied 
• Non-permitted concomitant medications that may meaningfully impact PD or safety 
outcomes 
• Meaningful dosing error 
• Randomization error 
The Investigator and Sponsor will both document this decision. The IRB/IEC will be informed of 
all important protocol deviations by the Investigator in accordance with established procedures. 
17.2. 
Publications 
No publication of the results shall take place without the Sponsor’s written consent. All 
publication or presentation rights for the findings of the clinical investigation under this protocol 
shall be governed by the appropriate terms of the clinical research agreement between the 
Investigator, the investigational site, and the Sponsor. 
The study will be registered on a publicly accessible website, in accordance with the applicable 
local laws and regulations.  
A summary of the results of the clinical study, together with a summary that is understandable to 
a layperson, will be made available within 1 year from the end of the clinical study. 
17.3. 
Change in Clinical Site Staff 
In the event that the Principal Investigator at a site is unable to continue the study, another 
suitable person will be designated as the Investigator, and documentation testifying to this will 
be submitted to the Sponsor or its designee within 10 days, who must approve the change along 
with the IRB/IEC before the study can be continued at that investigative site. 


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18. 
LIST OF REFERENCES 
 
Azimi E, Reddy VB, Lerner EA. Brief Communication: MRGPRX2, Atopic Dermatitis and Red 
Man Syndrome. Itch (Phila). 2017;2(1):e5. 
 
Babina M. The Pseudo-Allergic/Neurogenic Route of Mast Cell Activation via MRGPRX2: 
Discovery, Functional Programs, Regulation, Relevance to Disease, and Relation with Allergic 
Stimulation. Itch. 2020;5(2):e32. 
 
Basra MK, Salek MS, Camilleri L, et al. Determining the Minimal Clinically Important 
Difference and Responsiveness of the Dermatology Life Quality Index (DLQI): Further Data. 
Dermatology. 2015;230(1):27-33. 
 
Bissonnette R, Pavel AB, Diaz A, et al. Crisaborole and Atopic Dermatitis Skin Biomarkers: An 
Intrapatient Randomized Trial. J Allergy Clin Immunol. 2019;144(5):1274-89. 
 
Blair HA. Tralokinumab in Atopic Dermatitis: A Profile of Its Use. Clin Drug Investig. 
2022;42(4):365-74. 
 
Corbiere A, Loste A, Gaudenzio N. MRGPRX2 Sensing of Cationic Compounds-A Bridge 
Between Nociception and Skin Diseases? Exp Dermatol. 2021;30(2):193-200. 
 
Correale CE, Walker C, Murphy L, et al. Atopic Dermatitis: A Review of Diagnosis and 
Treatment. Am Fam Physician. 1999;60(4):1191-8. 
 
Deeks ED. Difelikefalin: First Approval. Drugs. 2021;81(16):1937-44. 
 
Eckert L, Gupta S, Gadkari A, et al. Burden of Illness in Adults with Atopic Dermatitis: Analysis 
of National Health and Wellness Survey Data from France, Germany, Italy, Spain, and the 
United Kingdom. J Am Acad Dermatol. 2019;81(1):187-95. 
 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--A Simple Practical Measure for 
Routine Clinical Use. Clin Exp Dermatol. 1994;19(3):210-6. 
 
Green DP, Limjunyawong N, Gour N, et al. A Mast-Cell-Specific Receptor Mediates 
Neurogenic Inflammation and Pain. Neuron. 2019;101(3):412-20 e3. 
 
Hadi HA, Tarmizi AI, Khalid KA, et al. The Epidemiology and Global Burden of Atopic 
Dermatitis: A Narrative Review. Life (Basel). 2021;11(9):1-19. 
 
Hamilton JD, Suarez-Farinas M, Dhingra N, et al. Dupilumab Improves the Molecular Signature 
in Skin of Patients with Moderate-to-Severe Atopic Dermatitis. J Allergy Clin Immunol. 
2014;134(6):1293-300. 
 
Hanifin JM, Rajka G. Diagnostic Features of Atopic Dermatitis. Acta Derm Venereol Suppl 
(Stockh) 1980;92:44-7. 


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Hanifin JM, Thurston M, Omoto M, et al. The Eczema Area and Severity Index (EASI): 
Assessment of Reliability in Atopic Dermatitis. EASI Evaluator Group. Exp Dermatol. 
2001;10(1):11-8. 
 
HHS. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 2017. p. 1-146. 
 
Howells LM, Chalmers JR, Gran S, et al. Development and Initial Testing of a New Instrument 
to Measure the Experience of Eczema Control in Adults and Children: Recap of atopic eczema 
(RECAP). Br J Dermatol. 2020;183(3):524-36. 
 
Kapp A, Czech W, Krutmann J, et al. Eosinophil Cationic Protein in Sera of Patients with Atopic 
Dermatitis. J Am Acad Dermatol. 1991;24(4):555-8. 
 
Magnifico I, Petronio Petronio G, Venditti N, et al. Atopic Dermatitis as a Multifactorial Skin 
Disorder. Can the Analysis of Pathophysiological Targets Represent the Winning Therapeutic 
Strategy? Pharmaceuticals (Basel). 2020;13(11):1-18. 
 
Meixiong J, Anderson M, Limjunyawong N, et al. Activation of Mast-Cell-Expressed Mas-
Related G-Protein-Coupled Receptors Drives Non-histaminergic Itch. Immunity. 
2019;50(5):1163-71 e5. 
 
Mikhaylov D, Ungar B, Renert-Yuval Y, et al. Oral Janus Kinase Inhibitors for Atopic 
Dermatitis. Ann Allergy Asthma Immunol. 2023;130(5):577-92. 
 
Morita H, Yamamoto K, Kitano Y. Elevation of Serum Major Basic Protein in Patients with 
Atopic Dermatitis. J Dermatol Sci. 1995;9(3):165-8. 
 
Nakamura Y, Oscherwitz J, Cease KB, et al. Staphylococcus Delta-Toxin Induces Allergic Skin 
Disease by Activating Mast Cells. Nature. 2013;503(7476):397-401. 
 
Nattkemper LA, Tey HL, Valdes-Rodriguez R, et al. The Genetics of Chronic Itch: Gene 
Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch. J Invest 
Dermatol. 2018;138(6):1311-7. 
 
Ogasawara H, Furuno M, Edamura K, et al. Peptides of Major Basic Protein and Eosinophil 
Cationic Protein Activate Human Mast Cells. Biochem Biophys Rep. 2020;21:100719. 
 
Paller AS, Tan JKL, Bagel J, et al. IGAxBSA Composite for Assessing Disease Severity and 
Response in Patients with Atopic Dermatitis. Br J Dermatol. 2022;186(3):496-507. 
 
Pavel AB, Song T, Kim HJ, et al. Oral Janus kinase/SYK Inhibition (ASN002) Suppresses 
Inflammation and Improves Epidermal Barrier Markers in Patients with Atopic Dermatitis. J 
Allergy Clin Immunol. 2019;144(4):1011-24. 
 


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Sahni VN, Balogh EA, Strowd LC, et al. The Evolving Atopic Dermatitis Management 
Landscape. Expert Opin Pharmacother. 2022;23(4):517-26. 
 
Serhan N, Basso L, Sibilano R, et al. House Dust Mites Activate Nociceptor-Mast Cell Clusters 
to Drive Type 2 Skin Inflammation. Nat Immunol. 2019;20(11):1435-43. 
 
Simon D, Vassina E, Yousefi S, et al. Reduced Dermal Infiltration of Cytokine-Expressing 
Inflammatory Cells in Atopic Dermatitis After Short-Term Topical Tacrolimus Treatment. J 
Allergy Clin Immunol. 2004;114(4):887-95. 
 
Simpson E, Bissonnette R, Eichenfield LF, et al. The Validated Investigator Global Assessment 
for Atopic Dermatitis (vIGA-AD): The Development and Reliability Testing of a Novel Clinical 
Outcome Measurement Instrument for the Severity of Atopic Dermatitis. J Am Acad Dermatol. 
2020;83(3):839-46. 
 
Subramanian H, Gupta K, Ali H. Roles of MAS-Related G Protein-Coupled Receptor-X2 
(MRGPRX2) on Mast Cell-Mediated Host Defense, Pseudoallergic Drug Reactions and Chronic 
Inflammatory Diseases. J Allergy Clin Immunol. 2016;138(3):700-10. 
 
Suh TP, Ramachandran D, Patel V, et al. Product of Investigator Global Assessment and Body 
Surface Area (IGAxBSA): A Practice-Friendly Alternative to the Eczema Area and Severity 
Index to Assess Atopic Dermatitis Severity in Children. J Am Acad Dermatol. 2020;82(5):1187-
94. 
 
Tameez Ud Din A, Malik I, Arshad D, et al. Dupilumab for Atopic Dermatitis: The Silver Bullet 
We Have Been Searching for? Cureus. 2020;12(4):e7565. 
 
Thapaliya M, Chompunud Na Ayudhya C, Amponnawarat A, et al. Mast Cell-Specific 
MRGPRX2: A Key Modulator of Neuro-Immune Interaction in Allergic Diseases. Curr Allergy 
Asthma Rep. 2021;21(1):3. 
 
Tofte S, Graeber M, Cherill R, et al. Eczema Area and Severity Index (EASI): A New Tool to 
Evaluate Atopic Dermatitis. J Eur Acad Dermatol Venereol. 1998;11(Suppl 2):S197. 
 
Wang Z, Babina M. MRGPRX2 Signals its Importance in Cutaneous Mast Cell Biology: Does 
MRGPRX2 Connect Mast Cells and Atopic Dermatitis? Exp Dermatol. 2020;29(11):1104-11. 
 
Wollam J, Solomon M, Villescaz C, et al., editors. MRPGRX2 Antagonist EP262 Prevents 
Inflammation and Disease in a Mouse Model of Atopic Dermatitis. American Academy of 
Dermatology Annual Meeting; 2023; Miami, Florida. 
 
Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: Psychometric 
Validation and Responder Definition for Assessing Itch in Moderate-to-Severe Atopic 
Dermatitis. Br J Dermatol. 2019;181(4):761-9. 
 


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Youngblood S, Tomasevic K. Atopic Dermatitis Skin Biopsies Have High Numbers of Activated 
Mast Cells that are Inhibited by AK002 after Stimulation Ex Vivo. J Allergy Clin Immunol. 
2020;145(2):AB198. 
 
Yu M, Terhorst-Molawi D, Altrichter S, et al. Omalizumab in Chronic Inducible Urticaria: A 
Real-Life Study of Efficacy, Safety, Predictors of Treatment Outcome and Time to Response. 
Clin Exp Allergy. 2021;51(5):730-4. 


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APPENDIX A. SCHEDULE OF ASSESSMENTS 
Assessment 
Screening 
Double-Blind Treatment 
Follow-Up Early Tx 
Terma 
Notes 
Visit 
Visit 1b 
Visit 2 
Visit 3  
Visit 4 
Visit 5c 
 
Study Day 
Days -30 to -7 
Day 1 
Day 22 
Day 43 
Day 71 
≤2 days 
after last 
dose 
Study Week  
 
Week 0 
Week 3 
Week 6 
Week 10 
Visit Window 
None 
None 
±3 days 
±3 days 
±3 days 
Screening or General Assessments 
Informed consent  
X 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
Includes AD disease history. 
Height 
X 
 
 
 
 
 
Should be measured using a stadiometer with no shoes. 
Body weight 
X 
 
 
X 
X 
X 
Should be measured with no shoes and heavy clothing 
(outdoor clothing such as coats) on and using a calibrated 
scale. 
HIV, HBV, HCV 
serology  
X 
 
 
 
 
 
 
Lesional skin swab 
X 
X 
X 
X 
 
 
Swab will be collected at Screening for bacterial culture to 
assess S. aureus colonization. At all other indicated visits, 
swabs will be collected for assessment of 
 
  
Eligibility check  
X 
X 
 
 
 
 
 
Randomization  
 
X 
 
 
 
 
Subjects will be randomized via IWRS in a 2:1 ratio to 
150 mg EP262 or placebo. 
Dispense study drug / 
administer dose at site 
 
X 
X 
 
 
 
Administer orally QD as intact capsules with approximately 
240 mL (8 fluid ounces) of water on an empty stomach. 
Collect study drug / 
assess study drug 
accountability and 
compliance 
 
 
X 
X 
 
X 
Subjects will record self-administration of study drug daily in 
a dosing diary that will be reviewed at each clinic visit during 
the Double-Blind Treatment Period following Visit 2 by 
clinical site staff. 
Provide electronic 
device/app training  
X 
 
 
 
 
 
 


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Assessment 
Screening 
Double-Blind Treatment 
Follow-Up Early Tx 
Terma 
Notes 
Visit 
Visit 1b 
Visit 2 
Visit 3  
Visit 4 
Visit 5c 
 
Study Day 
Days -30 to -7 
Day 1 
Day 22 
Day 43 
Day 71 
≤2 days 
after last 
dose 
Study Week  
 
Week 0 
Week 3 
Week 6 
Week 10 
Visit Window 
None 
None 
±3 days 
±3 days 
±3 days 
Safety Assessments 
Serum pregnancy testing 
X 
 
 
 
 
 
Required for all females.  
Urine pregnancy testing 
 
X 
X 
X 
X 
X 
Required for all females. 
Physical examination 
X 
 
 
X 
 
 
 
Abbreviated, symptom 
directed physical 
examination 
 
 
X 
 
X 
X 
Abbreviated, symptom directed physical examinations to 
assess clinically significant changes from Screening or any 
new signs or symptoms may be conducted at other visits as 
determined by the Investigator based on subject complaint. 
Standard 12-lead ECG 
X 
X 
 
X 
X 
X 
To be performed predose (as applicable) in a supine position 
after ≥5 min of rest. 
Vital signs 
X 
X 
X 
X 
X 
X 
Includes sitting systolic and diastolic blood pressure, pulse 
rate, body temperature, and respiratory rate, measured 
predose (as applicable) after ≥5 min of rest.  
Chemistry, hematology, 
and urinalysis 
X 
X 
X 
X 
X 
X 
Drawn after an overnight fast (≥8 hours) and predose (as 
applicable).  
Coagulation 
X 
X 
X 
X 
X 
X 
 
Concomitant 
medications  
X 
X 
X 
X 
X 
X 
Record all medications taken to treat AD beginning from the 
date of diagnosis and all other medications taken within 
30 days before Screening.  
AE assessment 
X 
X 
X 
X 
X 
X 
To be documented from the signing of the Informed Consent 
Form until the end of study participation. 
Pharmacodynamic Assessments 
Skin tape strips  
 
X 
X 
X 
 
 
To be repeated up to 20 times sequentially at predefined areas 
to collect samples from the stratum corneum for proteomic 
assessment. To be performed on AD lesional skin at all 
indicated visits and at a nonlesional site at Visit 2 (Day 1).  


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Assessment 
Screening 
Double-Blind Treatment 
Follow-Up Early Tx 
Terma 
Notes 
Visit 
Visit 1b 
Visit 2 
Visit 3  
Visit 4 
Visit 5c 
 
Study Day 
Days -30 to -7 
Day 1 
Day 22 
Day 43 
Day 71 
≤2 days 
after last 
dose 
Study Week  
 
Week 0 
Week 3 
Week 6 
Week 10 
Visit Window 
None 
None 
±3 days 
±3 days 
±3 days 
Photographs of AD 
lesions 
 
X 
X 
X 
X 
X 
Representative photographs will be taken of the area of worst 
lesional involvement at Visit 2 (Day 1) and of the same area 
at Visit 3 (Week 3), Visit 4 (Week 6), and Visit 5 (Follow-
Up). Photographs will also be taken of areas selected for skin 
swabs, skin tape strips application, and biopsies before these 
procedures are conducted. 
Stored plasma/serum 
 
X 
X 
X 
X 
X 
To be stored for future biomarker analyses. 


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Assessment 
Screening 
Double-Blind Treatment 
Follow-Up Early Tx 
Terma 
Notes 
Visit 
Visit 1b 
Visit 2 
Visit 3  
Visit 4 
Visit 5c 
 
Study Day 
Days -30 to -7 
Day 1 
Day 22 
Day 43 
Day 71 
≤2 days 
after last 
dose 
Study Week  
 
Week 0 
Week 3 
Week 6 
Week 10 
Visit Window 
None 
None 
±3 days 
±3 days 
±3 days 
Baseline Characterization 
Blood draw for HDM-
specific IgE 
 
X 
 
 
 
 
 
Genotyping 
 
X 
 
 
 
 
To evaluate UGT1A1 and filaggrin polymorphisms and 
enable pharmacogenomic analyses  
AD = atopic dermatitis; AE = adverse event; app = application; BSA = Body Surface Area; DLQI = Dermatology Life Quality Index; EASI = Eczema Area and 
Severity Index; ECG = electrocardiogram; HBV = hepatitis B virus; HCV = hepatitis C virus; HDM = house dust mite; HIV = human immunodeficiency virus; 
IgE = immunoglobulin E; IWRS = Interactive Web Response System; PK = pharmacokinetic; PP-NRS = Peak Pruritus Numeric Rating Scale; QD = once daily; 
RECAP = recap of atopic eczema; S. aureus = Staphylococcus aureus; Term = termination; Tx = treatment; UGT1A1 = uridine 5’ diphospho-
glucuronosyltransferase 1A1; vIGA-AD = validated Investigator Global Assessment for AD. 
Subjects will record emollient use in a daily diary throughout the study. 
Subjects should fast for at least 8 hours before study visits that require a blood sample for assessment of clinical chemistry. Water is acceptable in the morning of 
site visits to ensure the subject is hydrated for laboratory sample collection. Subjects should fast at least 4 hours before administration of each dose of study drug 
and refrain from eating for at least 2 hours postdose. Each dose of study drug is to be taken with approximately 240 mL (8 fluid ounces) of water on an empty 
stomach. 
a Early Treatment Termination Visit: Should be conducted as soon as possible after the last dose of study drug, ideally within 2 days after the last dose of study 
drug. 
b Screening Visit: May be conducted over more than 1 day but must be completed between Day -30 and Day -7. 
c Any subject who completes the Double-Blind Treatment Period or discontinues study drug (EP262 or placebo) early will have a Follow-Up Visit 
approximately 4 weeks (±3 days) after the last dose of study drug. 
 


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APPENDIX B. COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS 
The Common Terminology Criteria for Adverse Events (CTCAE) is widely accepted as the 
standard classification and severity grading scale for adverse events in cancer therapy, clinical 
trials, and other oncology settings. Version 5.0 is the most updated document (November 27, 
2017), and may be accessed using the following link:  
 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_8.5x11.pdf 


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APPENDIX H. SUMMARY OF CHANGES BY AMENDMENT 
Summary of Changes for Amendment 4.0 Dated 05 April 2024 
Protocol EP-262-202 was amended to extend (from 60 days to 84 days [12 weeks]) the duration after the last dose of study drug 
during which subjects with reproductive capability are restricted from egg/sperm donation and are to use acceptable forms of 
contraception. This modification is based on preliminary trends in emerging EP262 pharmacokinetic data from the ongoing clinical 
studies. The extension will remain in effect as a safety precaution until results from definitive reproductive and development toxicity 
studies of EP262 are available. 
This protocol amendment also includes an update regarding excluded medications and clarifies that only female subjects with a 
negative serum pregnancy test at Screening are eligible for participation in the study. 
Notable changes are included below in the summary table. Revised text in Amendment 4.0 is bolded, and text deleted from 
Amendment 3.0 is crossed out in the table below. Italicized text is used to describe a change. Minor/editorial changes are not listed 
individually in the summary table.   


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Section 
Amendment 3.0 
Amendment 4.0 
Reason for Change 
Synopsis, Inclusion Criteria 
8.1. Subject Inclusion 
Criteria 
4. If female, have a negative serum 
pregnancy test at Screening4, be willing to 
not donate eggs from Screening until 
60 days after the last dose of study drug, 
and:  
a. Is surgically sterile; or 
b. Has been amenorrhoeic for ≥1 year 
without an alternative medical cause; or 
c. If of childbearing potential5, must agree 
to use 2 forms of contraception, which 
includes at least 1 form of highly effective 
and 1 effective method6 of contraception 
from Screening until 60 days after the last 
dose of study drug.  
4 In instances when a serum pregnancy test 
result is confirmed to be indeterminate, the 
result should be discussed with the Escient 
medical team and interpreted by the 
Investigator using clinical judgment; it 
should not automatically result in screen 
failure. 
4. If female, must have a negative serum 
pregnancy test at Screening, be willing to 
not donate eggs from Screening until 
12 weeks after the last dose of study drug, 
and:  
a. Is surgically sterile; or 
b. Has been amenorrhoeic for ≥1 year 
without an alternative medical cause; or 
c. If of childbearing potential3, must agree 
to use 2 forms of contraception, which 
includes at least 1 form of highly effective 
and 1 effective method4 of contraception 
from Screening until 12 weeks after the last 
dose of study drug.  
Modified the duration after the last 
dose of study drug during which 
subjects with reproductive 
capability are restricted from 
egg/sperm donation and are to use 
acceptable forms of contraception 
based on preliminary trends in 
emerging EP262 pharmacokinetic 
data from the ongoing clinical 
studies.  
To clarify that only female subjects 
with a negative serum pregnancy 
test at Screening are eligible for  
participation in the study. 
Synopsis, Inclusion Criteria 
8.1. Subject Inclusion 
Criteria 
5. If male and is not confirmed surgically 
sterile, must be willing to not donate sperm 
and must agree to use a barrier method of 
contraception (eg, condom with 
spermicide) during intercourse and at least 
1 other acceptable contraceptive measure 
for his female partner(s) (eg, hormonal 
contraceptives, intrauterine device, female 
surgical sterilization, abstinence) from 
Screening through 60 days after the last 
dose of study drug 
5. If male and is not confirmed surgically 
sterile, must be willing to not donate sperm 
and must agree to use a barrier method of 
contraception (eg, condom with spermicide) 
during intercourse and at least 1 other 
acceptable contraceptive measure for his 
female partner(s) (eg, hormonal 
contraceptives, intrauterine device, female 
surgical sterilization, abstinence) from 
Screening through 12 weeks after the last 
dose of study drug 
Modified the duration after the last 
dose of study drug during which 
subjects with reproductive 
capability are restricted from 
egg/sperm donation and are to use 
acceptable forms of contraception 
based on preliminary trends in 
emerging EP262 pharmacokinetic 
data from the ongoing clinical 
studies.  
 


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Section 
Amendment 3.0 
Amendment 4.0 
Reason for Change 
Synopsis, Exclusion Criteria 
8.2. Subject Exclusion 
Criteria 
7. Use of the following prohibited 
medications within 2 weeks before Day 1: 
a. Drugs that are agonists at the 
MRGPRX2 receptor, including icatibant, 
opioids (eg, codeine, morphine), certain 
antidepressants/antipsychotics/antispasmo
dics (eg, paroxetine, clozapine, 
benztropine), or nondepolarizing 
neuromuscular blocking agents (eg, 
atracurium, rocuronium, vecuronium, 
cisatracurium, mivacurium)  
7. Use of the following prohibited 
medications within 2 weeks before Day 1: 
a. Drugs that are agonists at the MRGPRX2 
receptor, including icatibant, opioids (eg, 
codeine, morphine), clomipramine, or 
nondepolarizing neuromuscular blocking 
agents (eg, atracurium, rocuronium, 
vecuronium, cisatracurium, mivacurium)  
Revised the list of excluded 
agonists at the MRGPRX2 
receptor based on emerging data to 
remove those that are weak 
agonists of MRGPRX2.  
 
 


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Summary of Changes for Amendment 3.0 Dated 10 March 2024 
Protocol EP-262-202 was amended to address the following changes, including:  
• Remove the eligibility requirement for positive colonization of Staphylococcus aureus at Screening 
• Provide guidance regarding confirmed indeterminant pregnancy test results at Screening  
• Updates to the excluded concomitant medications 
• Reword the precautions regarding sun exposure 
Notable changes are included below in the summary table. Revised text in Amendment 3.0 is bolded, and text deleted from 
Amendment 2.0 is crossed out in the table below. Italicized text is used to describe a change. Minor/editorial changes are not listed 
individually in the summary table.   
Section 
Amendment 2.0 
Amendment 3.0 
Reason for Change 
Synopsis, Inclusion Criteria 
8.1 Subject Inclusion 
Criteria 
2.  Positive for colonization of S. aureus 
based on culturing of lesional skin swabs 
at Screening 
Deleted text 
Although testing for S. aureus 
colonization at Screening will still 
occur, the removal of requiring a 
positive result for study 
participation will increase subject 
eligibility without impacting 
safety. 
Synopsis, Inclusion Criteria 
8.1 Subject Inclusion 
Criteria 
5. If female, must have a negative serum 
pregnancy test at Screening and be willing 
to not donate eggs from Screening until 
60 days after the last dose of study drug 
and: 
4. If female, have a negative serum 
pregnancy test at Screening4, be willing to 
not donate eggs from Screening until 
60 days after the last dose of study drug, 
and: 
4 In instances when a serum pregnancy 
test result is confirmed to be 
indeterminate, the result should be 
discussed with the Escient medical team 
and interpreted by the Investigator using 
clinical judgment; it should not 
automatically result in screen failure. 
Guidance was provided to 
potentially allow women with a 
confirmed indeterminate result the 
opportunity to participate in the 
study, based on the Investigator’s 
clinical judgement. For instance, 
an indeterminant pregnancy test 
result in a surgically sterile or 
postmenopausal subject would not 
necessarily result in her inability to 
participate in the study.  


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Page 83 of 89 
Section 
Amendment 2.0 
Amendment 3.0 
Reason for Change 
Synopsis, Exclusion Criteria 
8.2 Subject Exclusion 
Criteria 
7. Use of the following prohibited 
medications within 2 weeks before Day 1: 
a. 
Drugs that are agonists at the 
MRGPRX2 receptor, including icatibant, 
opioids (eg, codeine, morphine), or 
antidepressants/antipsychotics/ 
antispasmodics (eg, doxepin, paroxetine, 
clozapine, benztropine)  
7. Use of the following prohibited 
medications within 2 weeks before Day 1: 
a. 
Drugs that are agonists at the 
MRGPRX2 receptor, including icatibant, 
opioids (eg, codeine, morphine), certain 
antidepressants/antipsychotics/ 
antispasmodics (eg, paroxetine, clozapine, 
benztropine), or nondepolarizing 
neuromuscular blocking agents (eg, 
atracurium, rocuronium, vecuronium, 
cisatracurium, mivacurium)  
Revised to clarify that only the use 
of antidepressants/antipsychotics/ 
antispasmodics that are agonists at 
the MRGPRX2 receptor are 
excluded. 
Doxepin was removed from the list 
of example antidepressants/ 
antipsychotics/antispasmodics 
given that it is a very weak agonist 
with a Cmax below the 
concentration needed to activate 
MRGPRX2. 
Nondepolarizing neuromuscular 
blocking agents are also agonists 
of the MRGPRX2 receptor and 
were added for completeness.  
Synopsis, Skin Swabs 
12.1 Skin Swabs 
A cotton swab will be passed along the 
lesional skin of the area of worst 
involvement at Screening. The skin swab 
will be placed in aerobic culture and 
analyzed for the presence of S. aureus to 
determine eligibility. 
A cotton swab will be passed along the 
lesional skin of the area of worst 
involvement at Screening. The skin swab 
will be placed in aerobic culture and 
analyzed for the presence of S. aureus. 
Although testing for S. aureus 
colonization at Screening will still 
occur, the removal of requiring a 
positive result for study 
participation will increase subject 
eligibility without impacting 
safety. 


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Page 84 of 89 
Section 
Amendment 2.0 
Amendment 3.0 
Reason for Change 
Appendix A. Schedule of 
Assessments (Lesional Skin 
Swab Row) 
Swab will be collected at Screening for 
bacterial culture to assess S. aureus 
colonization for eligibility. 
Swab will be collected at Screening for 
bacterial culture to assess S. aureus 
colonization. 
Although testing for S. aureus 
colonization at Screening will still 
occur, the removal of requiring a 
positive result for study 
participation will increase subject 
eligibility without impacting 
safety. 
 
 
 


EP-262-202 Protocol, Amendment 4.0 (05 April 2024) 
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Page 85 of 89 
Summary of Changes for Amendment 2.0 Dated 19 October 2023 
Protocol EP-262-202 was amended to address the following changes, including:  
• 
 
• Add abbreviated, symptom directed physical examinations at Visit 3 (Week 3), Visit 5 (Week 10), and the Early Treatment 
Termination Visit 
• Remove the requirement to measure the designated site for swabbing the skin 
• Remove the requirement to use a dedicated instrument to apply a defined pressure onto skin tape strips 
• 
 
• 
 
• Add glucose to the chemistry panel and clarify that dipsticks will not be used for urinalysis 
• Rearrange the rows in the scoring table for calculating the Eczema Area and Severity Index  
Notable changes are included below in the summary table. Revised text in Amendment 2.0 is bolded, and text deleted from the 
Amendment 1.0 is crossed out in the table below. Italicized text is used to describe a change. Minor/editorial changes are not listed 
individually in the summary table.   
Section 
Amendment 1.0 
Amendment 2.0 
Reason for Change 
Global change 
Included lipidomic analysis of skin tape 
strip samples  
Removed lipidomic analysis of skin tape 
strip samples 
Only proteomics will be analyzed 
from skin tape strip samples. 
Global change 
Symptom directed physical examinations 
were at the discretion of the Investigator 
Abbreviated, symptom directed physical 
examinations are now required at Visit 3 
(Week 3), Visit 5 (Week 10), and the Early 
Treatment Termination Visit, and may be 
conducted at the discretion of the 
Investigator for all other visits. 
Added the required abbreviated, 
symptom directed physical  
examinations to reflect feedback 
received from the US FDA. 
Synopsis, Skin Swabs 
12.1 Skin Swabs 
The designated site for swabbing will be 
measured for each subject, and the total 
area (cm × cm) recorded. 
Text was removed 
Removed text to reflect changes to 
the procedure for collecting 
microbes from skin.  


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Page 86 of 89 
Section 
Amendment 1.0 
Amendment 2.0 
Reason for Change 
Synopsis, Skin Tape Strips 
12.2 Skin Tape Strips 
A dedicated instrument will be used to 
apply a defined pressure onto the skin tape 
strip.  
Text was removed 
Removed text to reflect changes to 
the procedure for collecting skin 
tape strips. 
11.8 Laboratory Evaluations 
of Safety 
• Chemistry: sodium, albumin, alkaline 
phosphatase (ALP), bicarbonate, 
calcium, corrected calcium, chloride, 
bilirubin (total, indirect, and direct), 
AST, ALT, blood urea nitrogen, urea, 
creatinine, magnesium, phosphorus, 
potassium, creatine phosphokinase, total 
cholesterol, triglycerides, high-density 
lipoprotein cholesterol, low-density 
lipoprotein cholesterol, lactate 
dehydrogenase, gamma-
glutamyltransferase, and total protein 
Chemistry: sodium, albumin, alkaline 
phosphatase (ALP), bicarbonate, calcium, 
corrected calcium, chloride, bilirubin (total, 
indirect, and direct), AST, ALT, blood urea 
nitrogen, urea, creatinine, glucose, 
magnesium, phosphorus, potassium, 
creatine phosphokinase, total cholesterol, 
triglycerides, high-density lipoprotein 
cholesterol, low-density lipoprotein 
cholesterol, lactate dehydrogenase, gamma-
glutamyltransferase, and total protein 
Added glucose to the chemistry 
panel for completeness and to 
increase the robustness of safety 
screening and monitoring. 
11.8 Laboratory Evaluations 
of Safety 
• Urinalysis (dipstick): leukocyte esterase, 
nitrites, pH, protein, specific gravity, 
glucose, occult blood, ketones, bilirubin, 
and urobilinogen; microscopic analysis 
is to be performed only if protein, 
leukocyte esterase, blood or nitrite is 
positive 
• Urinalysis: leukocyte esterase, nitrites, 
pH, protein, specific gravity, glucose, 
occult blood, ketones, bilirubin, and 
urobilinogen; microscopic analysis is to 
be performed only if protein, leukocyte 
esterase, blood or nitrite is positive 
Corrected text to accurately reflect 
that dipsticks will not be used for 
urinalysis. 


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Section 
Amendment 1.0 
Amendment 2.0 
Reason for Change 
 
 
 


EP-262-202 Protocol, Amendment 4.0 (05 April 2024) 
Escient Pharmaceuticals, Inc. 
Confidential 
Page 88 of 89 
Summary of Changes for Amendment 1.0 Dated 02 August 2023 
Protocol EP-262-202 was amended to address the following changes, including:  
• Criteria for study drug discontinuation were updated  
• Photographs will not be taken until a subject is enrolled in the study, the protocol was updated accordingly 
• Urine albumin was removed from the urinalysis panel 
Notable changes are included below in the summary table. Revised text in Amendment 1.0 is bolded, and text deleted from the 
original version is crossed out in the table below. Italicized text is used to describe a change. Minor/editorial changes are not listed 
individually in the summary table.   
Section 
Original 
Amendment 1.0 
Reason for Change 
Title page 
Sponsor Statement 
New text 
Study Acronym: EASE 
The study acronym was added to 
further denote the study title. 
Synopsis, Study Drug 
Section 10.1, Study Drug 
Study Drug  
Capsules containing 75 mg of EP262 or 
placebo will be supplied in bottles in a 
manner to ensure the study blind. Each 
subject will take 2 capsules per dose for a 
total of 150 mg per day.    
Study Drug  
Capsules containing 75 mg of EP262 or 
placebo will be supplied in bottles in a 
manner to ensure the study blind. Each 
subject will take 2 capsules per dose, with 
subjects randomized to EP262 receiving a 
total of 150 mg per day.    
Text was added to clarify that only 
subjects randomized to the EP262 
group will receive active drug. 


EP-262-202 Protocol, Amendment 4.0 (05 April 2024) 
Escient Pharmaceuticals, Inc. 
Confidential 
Page 89 of 89 
Section 
Original 
Amendment 1.0 
Reason for Change 
Section 8.5.1, 
Discontinuation of Study 
Drug 
If a subject experiences a TEAE that is 
Common Terminology Criteria for 
Adverse Events (CTCAE) Grade 2 or 
higher in the Cardiac Disorders System 
Organ Class (SOC) or Grade 3 or higher in 
other SOCs and assessed as related to 
blinded study drug, the study drug must be 
discontinued. 
If a subject experiences a TEAE that is 
Common Terminology Criteria for Adverse 
Events (CTCAE) Grade 2 or higher in the 
Cardiac Disorders System Organ Class 
(SOC), Grade 2 or higher in CTCAE 
terms of Bone marrow hypocellular, 
Lymphocyte count decreased, 
Lymphocyte count increased, or 
Myelodysplastic syndrome, or Grade 3 or 
higher in other SOCs, the study drug must 
be discontinued. 
Incorporated per FDA 
recommendations on criteria for 
study drug discontinuation. 
Section 9.4.1.1, Visit 1 
(Day -30 to Day -7 
[inclusive]) 
Schedule of Events 
Photograph of site for skin swab was 
included in the Screening Visit list of 
procedures 
Photograph of site for skin swab was 
removed from Screening Visit list of 
procedures 
Photographs will only be taken 
once a subject is enrolled in the 
study. 
Section 11.8, Laboratory 
Evaluations of Safety 
• 
Urinalysis (dipstick): leukocyte 
esterase, nitrites, pH, protein, specific 
gravity, glucose, occult blood, ketones, 
bilirubin, urobilinogen, and albumin; 
microscopic analysis is to be performed 
only if protein, leukocyte esterase, blood 
or nitrite is positive 
• 
Urinalysis (dipstick): leukocyte 
esterase, nitrites, pH, protein, specific 
gravity, glucose, occult blood, ketones, 
bilirubin, and urobilinogen; microscopic 
analysis is to be performed only if protein, 
leukocyte esterase, blood or nitrite is 
positive 
Albumin is not a standard measure 
in urinalysis and not required for 
the safety evaluations in this study. 
 
 

SAP_001.pdf: 
Official Title: 
Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Safety, Tolerability, and Pharmacodynamics of EP262 in Subjects with Atopic 
Dermatitis 
NCT Number: 
NCT06144424 
Document Date: 
Statistical Analysis Plan EP-262-202 Version 1.0; 23 August 2024 
 
 
 


Escient Pharmaceuticals, Inc. 
Statistical Analysis Plan 
EP-262-202 
Version 1.0; 23 August 2024 
 
 
 
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Page 1 of 35 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
Escient Pharmaceuticals, Inc. 
EP-262-202 
 
 
 
 
 
 
Protocol Title: 
Phase 2a, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, and 
Pharmacodynamics of EP262 in Subjects with Atopic 
Dermatitis 
Protocol Version 
and Date: 
Amendment: 4.0; 05 April 2024 
Sponsor: 
Escient Pharmaceuticals, Inc. 
10578 Science Center Drive, Suite 250 
San Diego, CA 92121 USA 
Prepared By: 
 
 
Emanate Biostats, Inc. 
5800 Armada Drive, Suite 210 
Carlsbad, CA 92008 
Document 
Version and Date 
Version 1.0; 23 August 2024 
 
 


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Statistical Analysis Plan
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STATISTICAL ANALYSIS PLAN APPROVAL
Sponsor:
Escient Pharmaceuticals, Inc.
Clinical Protocol Number:
EP-262-202
Protocol Title:
Phase 2a, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Safety, 
Tolerability, and Pharmacodynamics of EP262 in 
Subjects with Atopic Dermatitis
Document File and Name:
Escient_EP-262-202_SAP_v1.0_2024-08-23.pdf
Document Version and 
Effective Date:
Version 1.0; 23 August 2024
Approved By:
, MS
, Biometrics and 
Data Analytics
Escient Pharmaceuticals, Inc.
, MS
, Clinical 
Development
Escient Pharmaceuticals, Inc.
 Biostatistics
Emanate Biostats, Inc.
Biostatistician I 
Emanate Biostats, Inc.


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EP-262-202 
Version 1.0; 23 August 2024 
 
 
 
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Page 3 of 35 
 
TABLE OF CONTENTS 
 
STATISTICAL ANALYSIS PLAN APPROVAL ........................................................ 2 
TABLE OF CONTENTS ............................................................................................... 3 
TABLE OF TABLES .................................................................................................... 5 
TABLE OF FIGURES ................................................................................................... 5 
ABBREVIATIONS ....................................................................................................... 6 
1. 
INTRODUCTION ................................................................................................. 8 
2. 
STUDY OBJECTIVES .......................................................................................... 8 
2.1 
Primary Study Objective ................................................................................. 8 
2.2 
Secondary Study Objective ............................................................................. 8 
2.3 
Exploratory Objectives .................................................................................... 8 
3. 
INVESTIGATIONAL PLAN ................................................................................ 9 
3.1 
Overall Study Design ...................................................................................... 9 
3.2 
Schedule of Assessments ................................................................................ 9 
3.3 
Treatment ........................................................................................................ 9 
3.3.1 
Treatment Administered .......................................................................... 9 
3.3.2 
Method of Assigning Subjects to Treatment Groups ............................. 10 
3.3.3 
Blinding Procedures ............................................................................... 10 
3.3.4 
Background Therapy Emollient Use ...................................................... 10 
3.3.5 
Rescue Medications ............................................................................... 11 
3.4 
Pharmacodynamic and Safety Variables ....................................................... 11 
3.4.1 
Pharmacokinetic Variables .................................................................... 11 
3.4.2 
Pharmacodynamic Variables ................................................................. 11 
3.4.3 
Baseline Characterization ...................................................................... 16 
3.4.4 
Safety Variables ..................................................................................... 16 
3.5 
Data Quality Assurance ................................................................................. 19 
4. 
STATISTICAL METHODS ................................................................................ 19 
4.1 
General Methodology .................................................................................... 19 
4.1.1 
Reporting Conventions .......................................................................... 19 
4.1.2 
Summarization by Visit ......................................................................... 20 
4.1.3 
Data Handling Rules .............................................................................. 21 
4.1.4 
Standard Calculations ............................................................................ 21 
4.2 
Analysis Sets ................................................................................................. 22 
4.3 
Study Subjects ............................................................................................... 23 
4.3.1 
Disposition of Subjects .......................................................................... 23 
4.3.2 
Protocol Deviations ................................................................................ 23 
4.4 
Statistical Evaluation ..................................................................................... 23 


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4.4.1 
Datasets Analyzed .................................................................................. 23 
4.4.2 
Demographic and Other Baseline Characteristics ................................. 23 
4.4.3 
Pharmacodynamic Analysis Methods .................................................... 24 
4.4.4 
Statistical/Analytical Issues ................................................................... 28 
4.4.5 
Plasma Concentrations ........................................................................... 29 
4.4.6 
Pharmacokinetic Analysis ...................................................................... 29 
4.5 
Safety Evaluation .......................................................................................... 29 
4.5.1 
Extent of Exposure ................................................................................. 29 
4.5.2 
Measurements of Treatment Compliance .............................................. 30 
4.5.3 
Adverse Events ...................................................................................... 30 
4.5.4 
Deaths, Other Serious Adverse Events, and Other Significant Adverse 
Events 31 
4.5.5 
Clinical Laboratory Evaluation .............................................................. 32 
4.5.6 
Vital Signs, Physical Findings, and Other Observations Related to 
Safety 32 
4.6 
Determination of Sample Size ....................................................................... 34 
4.7 
Changes in the Conduct of the Study or Planned Analyses .......................... 34 
5. 
REFERENCE LIST ............................................................................................. 35 
 
 
 


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TABLE OF TABLES 
Table 1 
List of Abbreviations ................................................................................... 6 
Table 2 
RECAP Total Score Calculation ............................................................... 15 
 
TABLE OF FIGURES 
Figure 1  EP-262-202 Study Design ........................................................................... 9 
 
 


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Version 1.0; 23 August 2024 
 
 
 
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ABBREVIATIONS 
Table 1 
List of Abbreviations 
Abbreviation 
Definition 
AD 
Atopic dermatitis  
AE 
Adverse event 
ANCOVA 
Analysis of Covariance 
ALT 
Alanine aminotransferase  
ALP 
Alkaline phosphatase 
ATC  
Anatomical Therapeutic Chemical 
AST 
Aspartate aminotransferase  
BLQ 
Below the limit of quantification 
BMI 
Body mass index 
BSA 
Body surface area 
CCL 
Chemokine ligands 
CONSORT 
Consolidated Standards of Reporting Trials 
CRO 
Contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CSR 
Clinical Study Report 
DE 
Differentially expressed 
DILI 
Drug-induced liver injury 
 
 
 
 
 
 
 
 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form  
EGF 
Epidermal growth factor 
FAS 
Full Analysis Set 
HDM 
House dust mite  
HEENT 
Head, eyes, ears, nose, throat 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IgE 
Immunoglobulin E 
IgG 
Immunoglobulin G 
IL 
Interleukins 
INR 
International normalized ratio 
IPD 
Important Protocol Deviation 
IWRS 
Interactive Web Response System 
 
 
Log2 
Log base 2 
LS 
Least-square 


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Abbreviation 
Definition 
LSMD 
Least-square mean difference 
MedDRA 
Medical Dictionary for Regulatory Activities 
 
 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic  
PP 
Per Protocol 
 
  
Q1 
1st quartile (25th percentile) 
Q3 
3rd quartile (75th percentile) 
QoL 
Quality of life 
QTcB 
Corrected QT interval using Bazett’s formula 
QTcF 
Corrected QT interval using Fridericia’s formula 
 
 
rlog 
Regularized log transformation 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
S. aureus 
Staphylococcus aureus 
TEAE 
Treatment-emergent adverse event 
TNF-α 
Tumor necrosis factor-alpha 
 
 
UGT1A1 
Uridine 5’ diphospho-glucuronosyltransferase 1A1 
ULN 
Upper limit of normal 
 
 
vst 
Variance stabilizing transformation 
WHO 
World Health Organization  
 
 


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1. INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide comprehensive and 
detailed descriptions of the methods and presentation of data analyses proposed for 
Escient Pharmaceuticals, Inc. Protocol EP-262-202 (Phase 2a, Randomized, Double-
Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and 
Pharmacodynamics of EP262 in Subjects with Atopic Dermatitis). Descriptions of 
planned analyses are provided in order to avoid post hoc decisions that may affect the 
interpretation of the statistical analysis. The statistical methods applied in the design 
and planned analyses of this study are consistent with the International Council for 
Harmonisation (ICH) guideline Statistical Principles for Clinical Trials (E9) (1998) 
and Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity 
Analysis in Clinical Trials (E9[R1], Rev 1) (2021).  
This SAP will be finalized prior to data analysis and before treatment unblinding and 
database lock to provide comprehensive details of the tables and listings to be presented 
in the Clinical Study Report (CSR). Any changes between the statistical methods 
provided in the clinical study protocol and this SAP will be explained herein; any 
changes or deviations from this SAP relative to the final analysis will be fully 
documented in the CSR. Minor changes or deviations from the templates for tables and 
listings need not be documented in the CSR. 
2. STUDY OBJECTIVES 
2.1 
Primary Study Objective 
The primary objective of this study is to evaluate the safety and tolerability of EP262 
compared to placebo in subjects with atopic dermatitis (AD).  
2.2 
Secondary Study Objective 
The secondary objective of this study is to evaluate the pharmacodynamic (PD) effects 
of EP262 compared to placebo in subjects with AD on skin biopsy-derived biomarkers. 
2.3 
Exploratory Objectives 


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3. INVESTIGATIONAL PLAN 
3.1 
Overall Study Design 
Study EP-262-202 is a Phase 2a, randomized, double-blind, placebo-controlled study 
to evaluate the safety, tolerability, and PD of EP262 over 6 weeks in subjects with AD. 
The study includes a Screening Period of at least a week and up to 30 days to assess 
subject eligibility that includes collection of daily 
 
(
) scores; a 6-week Double-Blind Treatment Period; and a 4-week Follow-Up 
Period after administration of the last dose of study drug for a total study duration of 
up to approximately 14 weeks for each subject. Approximately 30 subjects will be 
randomized in a 2:1 ratio to receive either a 150 mg dose of EP262 or placebo orally 
(PO), once daily (QD) during the 6-week Double-Blind Treatment Period (Figure 1). 
 
Figure 1  
EP-262-202 Study Design 
 
PO = oral; QD = once daily. 
a Any subject who completes the Double-Blind Treatment Period or discontinues study drug (EP262 or 
placebo) early will have a Follow-Up Visit approximately 4 weeks (±3 days) after the last dose of study 
drug. 
3.2 
Schedule of Assessments 
For the complete schedule of assessments, refer to Appendix A of the clinical study 
protocol. 
3.3 
Treatment 
3.3.1 Treatment Administered 
Capsules containing 75 mg of EP262 or placebo will be supplied in bottles in a manner 
to ensure the study blind. Each subject will take 2 capsules per dose, with subjects 
randomized to EP262 receiving a total of 150 mg per day.  
Each study drug dose is to be administered PO as intact capsules (swallowed whole, 
not split, opened, or chewed) and taken with approximately 240 mL (8 fluid ounces) of 
water on an empty stomach. Subjects will be instructed to take the study drug at 
approximately the same time of the day after a fast of at least 4 hours. Subjects should 
refrain from eating for at least 2 hours postdose. On the days of clinic visits, the time 
of study drug administration may differ depending on the scheduled visit time. The first 
Enroll/Randomize
Visit 2
Day 1
Placebo PO QD (N=10)
Screening
Visit 1
Days -30 to -7
Follow-Up 
Visit 4
Week 6
Screening Period
Double-Blind Treatment Period
Follow-Up Period
150 mg EP262 PO QD (N=20)
Visit 3
Week 3
Visit 5a
Week 10


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dose of study drug will be administered at the clinical site on Visit 2 (Day 1) after all 
baseline study procedures are completed. 
3.3.2 Method of Assigning Subjects to Treatment Groups 
Approximately 30 subjects with AD will be randomized in a 2:1 ratio to receive either 
a 150 mg dose of EP262 or placebo PO, QD for 6 weeks during the Double-Blind 
Treatment Period beginning at Visit 2 (Day 1). Randomization will be conducted 
centrally via an Interactive Web Response System (IWRS). The master randomization 
list will be kept secured until the study blind is broken at the end of study. 
Subjects who withdraw for any reason without completing all screening evaluations 
successfully will be considered “screening failures”. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure subjects, to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements, and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any 
serious adverse events (SAEs). 
3.3.3 Blinding Procedures 
The Sponsor, Medical Monitor, Contract Research Organization (CRO) staff, 
Investigators, site staff, and subjects will be blinded to subject’s assigned treatment 
until the database is locked except for CRO or vendor staff involved in the analysis of 
pharmacokinetic samples. Procedures for emergency unblinding and unblinding for 
regulatory reporting are described below. 
If an emergency unblinding during the Double-Blind Treatment Period is required, the 
subject’s treatment assignment may be unblinded through IWRS by the Investigator. If 
a treatment assignment is unblinded, the subject will be discontinued from randomized 
treatment. 
Blinding codes should only be broken in emergency situations for reasons of subject 
safety and when knowledge of the treatment assignment will impact the clinical 
management of the subject. Every reasonable attempt should be made to complete the 
post-treatment evaluation procedures prior to unblinding as knowledge of the treatment 
arm could influence subject assessment. In all emergency cases, the reasons and 
rationale for unblinding will be documented in writing and maintained in the study file. 
Access to randomization codes and corresponding treatment assignment will be made 
available through the IWRS system to the appropriate individual(s) responsible for 
unblinding suspected unexpected serious adverse reactions for reporting to the 
Regulatory Authorities. 
3.3.4 Background Therapy Emollient Use 
Subjects are to use a protocol-permitted, non-urea-containing emollient on lesional and 
nonlesional skin daily for at least 1 week before Day 1 and agree to continue using that 
same emollient daily at the same frequency (ideally once or twice daily) throughout the 
study. Subjects will record emollient use in a daily diary throughout the study. Every 


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effort should be made to keep the same emollient throughout the study for the same 
body region. 
Subjects will delay emollient use on the days of study visits until after study procedures 
are completed. 
3.3.5 Rescue Medications  
New concomitant medications and procedures for treatment of AD are prohibited 
during the study. If a patient requires treatment with a new medication or procedure due 
to intolerable AD symptoms, study drug should be discontinued. Whenever possible, 
subjects should remain in the study and complete the remaining study visits and 
assessments even when study drug has been discontinued. 
3.4 
Pharmacodynamic and Safety Variables 
3.4.1 Pharmacokinetic Variables 
Blood sampling will be collected predose (as applicable) at Visit 2 (Day 1), and each 
visit thereafter to analyze trough EP262 concentrations. The EP262 metabolite profile 
may also be analyzed from these trough samples. 
3.4.2 Pharmacodynamic Variables 
Pharmacodynamic assessments 
 
 
 
 
 
 
 
 be taken of the area of worst lesional involvement at 
Visit 2 (Day 1) and of the same area at Visit 3 (Week 3), Visit 4 (Week 6), and Visit 5 
(Follow-Up). Photographs will also be taken of areas selected for skin swabs, skin tape 
strips application, and biopsies before these procedures are conducted. 


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3.4.3 Baseline Characterization 
A blood sample will be collected at Visit 2 (Day 1) for measurement of house dust mite 
(HDM)-specific IgE. 
Blood samples will also be taken at Visit 2 (Day 1) for genotyping to evaluate uridine 
5’ diphospho-glucuronosyltransferase 1A1 (UGT1A1) and filaggrin polymorphisms to 
enable pharmacogenomic analyses. 
3.4.4 Safety Variables 
Safety evaluations, including adverse events (AEs), concomitant medications, medical 
history, vital signs, physical examinations, standard 12-lead electrocardiograms 
(ECGs), and laboratory evaluations of safety will be performed as indicated in the 
Schedule of Assessments (Appendix A) of the clinical study protocol. 
3.4.4.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable or unintended sign (including 
a clinically significant abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product. 
Medical conditions present at baseline that worsen in severity or frequency after 
exposure to study drug are considered treatment-emergent adverse events (TEAEs). A 
TEAE is any condition that was not present prior to treatment with the study drug 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). Planned hospital admissions or surgical procedures for an 


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illness or a disease that existed before administration of study drug, and for which the 
condition has not worsened since starting study drug, are not to be considered 
TEAEs/treatment-emergent serious AEs. Events with emergency room visits that are 
less than 24 hours will also not be considered SAEs unless they meet one of the criteria 
listed in Section 11.2.1 of the clinical study protocol.  
Abnormal laboratory tests, 12-lead ECG assessments, or vital sign results may 
constitute an AE if they meet one of the criteria listed in Section 11.1.4.1 of the clinical 
study protocol. However, whenever possible, the underlying diagnosis should be listed 
in lieu of associated abnormal results.  
Subjects will be assessed for potential drug-induced liver injury (DILI) during the 
study, although there was no evidence of hepatotoxicity in previous studies related to 
EP262. Monitoring, interruption, and stopping rules based on multiples of the upper 
limit of normal (ULN) of aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), and total bilirubin values are described in section 11.10.3 of the clinical study 
protocol.  
AEs are graded for severity (i.e., intensity) using Common Terminology Criteria for 
Adverse Events (CTCAE), version 5.0 (HHS 2017). A severity category of mild, 
moderate, severe, life-threatening, or death, as defined in Appendix B of the clinical 
study protocol, will be entered on the AE Electronic Case Report Form (eCRF). 
Additional considerations are made for TEAEs falling under certain system organ 
classes. The study drug must be discontinued for the following TEAEs and CTCAE 
grades:  
• CTCAE Grade 2 or higher in the Cardiac Disorders system organ class 
• CTCAE Grade 2 or higher in terms of Bone marrow hypocellular, lymphocyte 
count decreased, lymphocyte count increased, or myelodysplastic syndrome 
• CTCAE Grade 3 or higher in other system organ classes 
3.4.4.2 
Laboratory Parameters 
Samples for the following laboratory tests should be collected after an overnight fast 
(at least 8 hours): 
• Chemistry: sodium, albumin, alkaline phosphatase (ALP), bicarbonate, 
calcium, corrected calcium, chloride, bilirubin (total, indirect, and direct), AST, 
ALT, blood urea nitrogen, urea, creatinine, glucose, magnesium, phosphorus, 
potassium, creatine phosphokinase, total cholesterol, triglycerides, high-density 
lipoprotein 
cholesterol, 
low-density 
lipoprotein 
cholesterol, 
lactate 
dehydrogenase, gamma-glutamyl transferase, and total protein 
• Hematology: hemoglobin, hematocrit, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration, mean corpuscular volume, white blood 
cell count (total and differential), red blood cell count, platelet count, and 
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• Urinalysis: leukocyte esterase, nitrites, pH, protein, specific gravity, glucose, 
occult blood, ketones, bilirubin, and urobilinogen; microscopic analysis is to be 
performed only if protein, leukocyte esterase, blood or nitrite is positive 
• Coagulation: activated partial thromboplastin time, international normalized 
ratio (INR), and prothrombin time 
• Pregnancy testing: required for all females; serum test at Screening (Visit 1) and 
urine test for all other visits where pregnancy testing is required 
The urine pregnancy test for female subjects will be conducted locally; all other planned 
laboratory evaluations of safety will be conducted at a central laboratory. Details for 
sample collection, processing, storage, and shipment will be provided in the Laboratory 
Manual. 
3.4.4.3 
Other Laboratory Evaluations 
Samples for the following laboratory tests will be collected: 
• Serology: HIV I/II, HBV (hepatitis B surface antigen), HCV 
These planned laboratory evaluations will be conducted at a central laboratory. See the 
Laboratory Manual for additional details. 
3.4.4.4 
Medical History 
The Investigator or designee will collect and review the subject’s medical history, 
including AD disease history, to evaluate the subject’s eligibility for study 
participation. The new onset of signs, symptoms, or other findings that occur from 
before signing of the informed consent form (ICF) will be captured as medical history. 
3.4.4.5 
Vital Signs 
Vital signs, including sitting systolic and diastolic blood pressure, pulse rate, body 
temperature, and respiratory rate, will be measured pre-dose (as applicable) after at least 
5 minutes of rest. Vital signs are to be performed pre-dose if the dose is administered 
at the site. 
3.4.4.6 
Body Weight and Height 
Body weight should be measured with no shoes and heavy clothing (outdoor clothing 
such as coats) on and using a calibrated scale throughout the study. Height should be 
measured using a stadiometer with no shoes. 
3.4.4.7 
Physical Examinations 
Physical examinations will include but are not limited to an assessment of general 
appearance, skin, HEENT (head, eyes, ears, nose, throat), musculoskeletal, 
thyroid/endocrine, 
cardiovascular, 
chest/lung, 
neurologic, 
abdomen, 
and 
extremities/general body systems. 


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Abbreviated, symptom-directed physical examinations to assess clinically significant 
changes from Screening or any new signs or symptoms will be conducted at Visit 3 
(Week 3), Visit 5 (Week 10), and the Early Treatment Termination Visit, and may be 
conducted at other visits as determined by the Investigator based on subject complaint. 
Clinically significant abnormalities from before signing of the ICF will be recorded as 
medical history, and clinically significant changes after signing the ICF will be recorded 
as AEs. 
3.4.4.8 
12-Lead Electrocardiograms 
Twelve-lead ECGs are to be performed pre-dose (as applicable) with subjects in a 
supine position after at least 5 minutes of rest. An ECG is to be performed pre-dose if 
the dose is administered at the site. 
3.5 
Data Quality Assurance 
Report summaries will be generated using validated Base SAS® software, version 9.4 
or higher, on a PC or server-based platform. Additional validated software may be used 
to generate analyses, as needed.  
All SAS programs that create outputs or supporting analysis datasets will be validated 
by a second statistical programmer or biostatistician. At a minimum, validation of 
programs will consist of a review of the program log, review of output or dataset format 
and structure, and independent confirmatory programming to verify output results or 
dataset content. Additionally, all outputs will undergo a review by a senior level team 
member before finalization. 
The content of the source data will be reviewed on an ongoing basis by project statistical 
programmers and statisticians. Data will be checked for missing values, invalid records, 
and extreme outliers through defensive programming applications, analysis-based edit 
checks, and other programmatic testing procedures. All findings will be forwarded to 
the project data manager for appropriate action and resolution. 
4. STATISTICAL METHODS 
4.1 
General Methodology 
Data will be analyzed by Emanate biostatistics personnel. Statistical analyses will be 
reported with tables and listings, presented in rich text format, and using recommended 
ICH numbering. Output specifications for all tables and listings will be in conformance 
with guidelines specified by the ICH in Appendix 7 of the Electronic Common 
Technical Document Specification (Apr 2003). 
4.1.1 Reporting Conventions 
Tables will be summarized by treatment group. All tables, exclusive of PD and 
pharmacokinetic (PK) analyses, will also include a column for all subjects combined. 
In general, all data collected and any derived data will be presented in subject data 
listings, for all enrolled subjects. Listings will be ordered by subject number, treatment 


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group, and assessment or event date. The treatment group presented in listings will be 
based on the planned assignment, unless otherwise noted. 
In general, continuous variables will be summarized to indicate the study population 
sample size (N), number of subjects with available data (n), mean, SD, SE, median, 
first (Q1) and third (Q3) quartiles, minimum, and maximum values. Categorical 
variables will be summarized by the population size (N), number of subjects with 
available data (n), number of subjects in each category, and the percentage of subjects 
in each category. Unless otherwise noted, the denominator to determine the percentage 
of subjects in each category will be based on the number of subjects with available data. 
Select ordinal data may be summarized using both descriptive statistics and counts and 
percentages of subjects in each category, as appropriate. 
Non-zero percentages will be rounded to one decimal place. Rounding conventions for 
presentation of summary statistics will be based on the precision of the variable of 
summarization, as it is collected in its rawest form (i.e., on the eCRF or as provided 
within an external file) and are outlined as follows: 
• The mean and median will be rounded to one more decimal place than the 
precision of the variable of summarization; 
• Measures of variability (e.g., SD, SE) will be rounded to two more decimal 
places than the precision of the variable of summarization; and 
• Minimum and maximum values will be presented using the same precision as 
the variable of summarization. 
Other statistics (e.g., CIs) will be presented using the same general rules outlined above, 
or assessed for the most appropriate presentation based on the underlying data. 
No formal statistical analysis will be performed to compare treatment groups. This 
study is exploratory in nature; descriptive statistics will be tabulated by treatment group 
and reviewed to evaluate all study endpoints. Any p-values presented are to be 
considered nominal in their evaluation and interpretation. P-values will be reported for 
statistical tests, rounded to four decimal places. P-values less than 0.0001 will be 
displayed as “<0.0001”; p-values greater than 0.9999 will be displayed as “>0.9999”. 
4.1.2 Summarization by Visit 
Data summarized by study visit will be based on the nominal, scheduled visit label as 
reported on the eCRF.  
Whenever possible, subjects should remain in the study and complete the remaining 
study visits and assessments even when study drug has been discontinued. Subjects who 
discontinue study drug for any reason and continue with the study visits as planned 
through Visit 4 (Week 6) (participating only in PD and safety, but not PK measures) 
will participate in the Follow-Up Visit if the last dose of study drug was administered 
less than 4 weeks before Visit 4 (Week 6) to ensure that at least 4 weeks of follow-up 
data are collected for all randomized subjects. Subjects that discontinue treatments early 
and complete the remaining study visits will be summarized according to their planned 
treatment group, unless otherwise noted.  


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If a subject discontinues study drug and chooses not to complete all of the remaining 
study visits, the subject should have the Early Treatment Termination visit conducted 
as soon as possible after the last dose of study drug, ideally within 2 days after the last 
dose of study drug, and a Follow-Up Visit approximately 4 weeks (±3 days) after the 
last dose of study drug if at least 4 weeks of follow-up data have not already been 
collected. The Early Treatment Termination visit will be mapped and summarized with 
the next treatment scheduled nominal visit, according to the schedule of events, based 
on the last visit completed per protocol if the Early Treatment Termination visit falls 
within the study day visit window defined for that nominal visit.  
Data collected at unscheduled visits will not be included in by-visit summaries, but will 
be considered when endpoint derivations potentially include multiple visits (e.g., 
determination of baseline value, determination of worst post-baseline value, etc.). All 
data will be included in subject listings. 
4.1.3 Data Handling Rules 
Unless otherwise noted, values reported as greater than or less than some quantifiable 
limit (e.g., “< 1.0”) will be summarized with the sign suppressed in summary tables, 
using the numeric value reported. Data will display on subject listings to include the 
sign. 
4.1.4 Standard Calculations 
Where appropriate, the calculated study day of each assessment or event will be 
presented with the assessment or event date on subject data listings, where study day 
will be determined as: 
• The assessment/event date minus the date of first dose of study drug, if the 
assessment/event date is prior to the date of first dose; and 
• The assessment/event date minus the date of first dose of study drug, plus one, 
if the assessment/event date is on or after the date of first dose. 
Other variables requiring calculations will be derived using the following formulas: 
• Days: A duration between two dates expressed in days will be calculated using 
the following conventions: 
o Later date – earlier date + 1, if the earlier date is on or after the reference 
date of interest (e.g., date of first dose of study drug); or 
o Later date – earlier date, if the earlier date is prior to the reference date 
of interest. 
• Months: A duration expressed in months will be calculated by dividing the 
duration in days by (365.25 / 12). 
• Years: A duration expressed in years will be calculated by dividing the duration 
in days by 365.25. 


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• Change from Baseline: Change from baseline will be calculated as the post 
baseline value minus the baseline value. 
• Percentage Change from Baseline: Percentage change from baseline will be 
calculated as the change from baseline divided by the baseline value, multiplied 
by 100. 
• Geometric CV: calculated as 100*sqrt[exp(σ2)-1], where σ2 is the variance of 
the log-transformed data. 
• Log2 Fold Change: calculated as B - A, where: B is the value of interest and A 
is the value of reference, where B and A are log scale base 2 transformed. 
4.2 
Analysis Sets 
The analysis sets are defined as follows:  
• Full Analysis Set: All subjects who are randomized and take at least 1 dose of 
randomized study drug will be included in the Full Analysis Set (FAS). Subjects 
in the FAS will be analyzed according to randomized treatment assignment. All 
PD analyses will be based on the FAS. 
• Per Protocol Set: The Per Protocol (PP) Set is a subset of the FAS containing 
subjects who meet study eligibility requirements and had no protocol deviations 
that might impact the assessment of PD measurements. Subjects will be 
analyzed according to randomized treatment assignment. The PP Set will be 
used for sensitivity analyses relating to PD. Protocol deviations that qualify for 
exclusion from the PP Set include: 
o Deviations of inclusion/exclusion criteria 
o Non-permitted concomitant medications or procedures that may 
meaningfully impact PD outcomes  
o Meaningful dosing and/or randomization error(s) 
o Any other important protocol deviation deemed by the Sponsor to 
warrant exclusion from the PP set 
Any protocol deviations that govern exclusion from the PP Set will be 
determined prior to database lock. 
• Safety Analysis Set: All subjects who are randomized and take at least 1 dose 
of randomized study drug will be included in the Safety Analysis Set. Safety 
analyses will be based upon treatment actually received. 
• PK Set: All subjects who receive at least 1 dose of EP262 and provide adequate 
blood samples for bioanalysis will be included in the PK Set. 
Data summaries to be presented on both the Safety Analysis Set and the FAS will only 
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4.3 
Study Subjects 
4.3.1 Disposition of Subjects 
Subject disposition will be summarized for all randomized subjects by treatment group 
and overall subjects combined. Summaries will include the number and percentage of 
subjects in each analysis set, completing the study, and discontinuing the study early 
by the primary reason for discontinuation. Subject disposition will also be summarized 
separately for each study site for all randomized subjects. 
The number and percentage of screen failures will be presented based on the total 
number of subjects screened. The reason for screen failure will also be summarized for 
screen failures. Screen failures will also be presented in a subject-level listing.  
4.3.2 Protocol Deviations 
Important Protocol Deviations (IPDs) will be summarized by treatment group and 
overall subjects combined for the FAS. Important Protocol Deviations are identified by 
the Sponsor and are defined in the ICH guideline Structure and Content of Clinical 
Study Reports – Questions and Answers (E3[R1], 2013) as a subset of protocol 
deviations that might significantly affect the completeness, accuracy, and/or reliability 
of the study data or that might significantly affect a subject’s rights, safety, or well-
being.  
All IPDs will be determined and appropriately categorized prior to database lock and 
prior to breaking the blind of the treatment group assignments. The number and 
percentage of subjects with any IPDs as well as the number and percentage of subjects 
with IPDs within each category will be presented. A listing of important protocol 
deviations will be provided. 
4.4 
Statistical Evaluation 
4.4.1 Datasets Analyzed 
All PD summaries will be based on the FAS; select summaries will also be produced 
on the PP Set. A data listing of subjects excluded from the FAS or PP Set, to include 
the reason for exclusion, will be presented. 
4.4.2 Demographic and Other Baseline Characteristics 
Demographic variables including age, sex, ethnicity and race will be summarized by 
treatment group and overall subjects combined for the Safety Analysis Set, FAS, PP 
Set, and PK Set.  
Age will be summarized using descriptive statistics. Sex, ethnicity, and race will be 
summarized with the number and percentage of subjects in each parameter category. 
Medical history conditions will be mapped to preferred terms and system organ classes 
using the Medical Dictionary for Regulatory Activities (MedDRA, version 26.0). 
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system organ class and preferred term will be presented for the FAS and summarized 
by treatment group and overall subjects combined. 
Baseline disease characteristics to be summarized include baseline total IgE (kU/L), 
time since AD diagnosis (as reported on the Disease History eCRF), presence of S. 
aureus, history of asthma, allergic rhinitis, HDM allergy, whether or not the subject has 
had phototherapy for AD, previously taken other AD medications, or has taken any 
emollients after diagnosis. The number and percentage of subjects with a baseline total 
IgE greater than 100 kU/L will also be summarized. Time since AD diagnosis (in years) 
is calculated as the informed consent date – the date of diagnosis divided by 365.25. 
Subjects with partial dates reported for the date of diagnosis will have time (years) 
calculated utilizing the available date information reported. Time since AD diagnosis 
will be summarized using descriptive statistics. Baseline characteristics will be 
summarized for the Safety Analysis Set, FAS, PP Set, and PK Set by treatment group 
and overall subjects combined. 
Prior reported AD therapies will be coded using the World Health Organization (WHO) 
Drug Global B3, version March 1, 2023. Therapies entered on the Prior AD eCRF will 
be mapped to Anatomical Therapeutic Chemical (ATC) drug class (level 2) and 
preferred name. The number and percentage of subjects receiving any therapy will be 
summarized by treatment group and overall subjects combined in the FAS, as will the 
number and percentage receiving any therapy by ATC drug class and preferred name. 
Subjects reporting use of more than one therapy at each level of summarization (any 
medication received, ATC class, and preferred name) will be counted only once.  
Baseline characterization data including UGT1A1, filaggrin polymorphisms, and total 
HDM – specific IgE will be presented in a listing. 
4.4.3 Pharmacodynamic Analysis Methods 


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4.4.4 Statistical/Analytical Issues 
4.4.4.1 
Adjustments for Covariates 
The ANCOVA model to compare treatment groups for the skin biopsy-derived 
biomarkers secondary endpoint of skin histology will include a covariate adjustment 
for the baseline value. All statistical results presented are to be considered nominal in 
their evaluation and interpretation. 
4.4.4.2 
Handling of Dropouts or Missing Data 
No imputations will be performed on missing data; all analyses will be descriptive in 
nature and based on observed data only. Any responder analysis will be based on the 
number of subjects reporting data at the visit of interest.  
4.4.4.3 
Interim Analyses and Data Monitoring 
No interim analysis will take place for the study.  
4.4.4.4 
Multicenter Studies 
This is a multicenter study to be conducted within North America. Pharmacodynamic 
data collected from all study sites will be pooled for data analysis. The effect of study 
site on the analysis results may be explored post-hoc, as needed. 
4.4.4.5 
Multiple Comparisons/Multiplicity 
For analysis of gene expression, the Bonferroni correction will be used to control the 
alpha at 5%. For analysis of other parameters, there will be no adjustments for multiple 
comparisons in the analysis for this study. Results are descriptive in nature and there 
will be no formal comparisons made among treatment groups. All statistical results 
presented are to be considered nominal in their evaluation and interpretation. 
4.4.4.6 
Use of an “Efficacy Subset” of Subjects 
The primary analysis will be performed on the FAS; the PP Set will be utilized as a 
sensitivity analysis. The PP Set will exclude subjects with IPDs. 
4.4.4.7 
Active-Control Studies Intended to Show Equivalence 
This study does not include an active-control product and is not intended to demonstrate 
equivalence between any two drug products. 


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Additional subgroup analyses may be performed post-hoc, as appropriate. 
4.4.5 Plasma Concentrations 
Raw plasma concentration values will be summarized for the PK Set by treatment group 
and sampling time point using descriptive statistics, to include the geometric mean and 
CV (%). For summaries of plasma concentrations, below the limit of quantification 
(BLQ) values will be set to missing. The number and percentage of subjects with BLQ 
values will be summarized by time point and treatment group. 
4.4.6 Pharmacokinetic Analysis 
Pharmacokinetic analysis is based on the analysis of plasma concentrations of EP262 
as described in Section 4.4.5. 
4.5 
Safety Evaluation 
Safety analysis will be carried out for the Safety Analysis Set, to include all subjects 
who receive at least one dose of study drug. Subjects who do not complete the study, 
for whatever reason, will have all available data up until the time of termination 
included in the analysis, as described in Section 4.1.2. For safety analysis presented by 
study visit, the baseline value will be defined as the last value reported prior to first 
dose of study drug. 
4.5.1 Extent of Exposure 
Extent of exposure to study treatment will be summarized for the Safety Analysis Set 
by treatment group and overall subjects combined. The duration of exposure will be 
presented in days and calculated as the date of last dose of study drug minus the date of 
first dose of study drug, plus one. Total dose received (mg) will be determined as the 
summation of all entries of “Dispensed Amount (Capsules)” reported on the “Drug 
Accountability – Dispensed” eCRF minus the summation of all entries of “Amount 
Returned (Capsules)” reported on the “Drug Accountability – Returned” eCRF. Any 
capsules reported as lost will be further subtracted from this total. Subjects that are 
missing their return records are assumed to have taken all dispensed capsules for the 
missing bottle. The number of capsules taken is then multiplied by 75 to obtain the total 
dose received (mg). Duration of exposure and total dose received (mg) will be 
summarized using descriptive statistics.  


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4.5.2 Measurements of Treatment Compliance 
4.5.2.1 
Study Treatment Compliance 
Compliance to the study treatment regimen will be based on the drug accountability 
records. Compliance will be determined as the percentage of expected capsules that a 
subject should have taken based on their dosing days on study relative to the drug 
accountability reporting of their actual number of capsules taken. The following 
definitions are applied:  
• Expected Number of Dosing Days: the last dose date reported on the End of 
Treatment eCRF minus the onsite first study administration that takes place at 
Visit 2 (Day 1) + 1. 
• Expected Number of Capsules to be Taken: Expected Number of Dosing Days 
multiplied by two (standard dosing includes two capsules per day). 
• Actual Number of Capsules Taken: The summation of all entries of “Dispensed 
Amount (Capsules)” reported on the “Drug Accountability – Dispensed” eCRF 
minus the summation of all entries of “Amount Returned (Capsules)” reported 
on the “Drug Accountability – Returned” eCRF. Any capsules reported as lost 
will be further subtracted from this total. Subjects that are missing their return 
records are assumed to have taken all dispensed capsules for the missing bottle.  
Treatment compliance (%) is defined as the Actual Number of Capsules Taken divided 
by the Expected Number of Capsules to be Taken, multiplied by 100.  
Dosing compliance will be summarized using descriptive statistics, by treatment group 
and overall subjects combined, for the Safety Analysis Set. The number and percentage 
of subjects who are < 80% compliant and ≥ 80% compliant within each treatment group 
and overall subjects combined will be summarized. 
4.5.2.2 
Emollient Use 
Subject exposure to on-study background therapy emollient-use will be summarized by 
treatment group and overall subjects combined for the Safety Analysis Set. The number 
and percentage of subject’s reporting use of a non-study permitted emollient at any time 
on study will be summarized based on self-reporting of emollient use by the daily diary. 
Summarization of concomitant emollient based on the medication reported will also be 
provided as described in Section 4.5.6.4. 
4.5.3 Adverse Events 
A TEAE is defined as those AEs with onset after the first dose of study drug or existing 
events that worsened after the first dose during the study. Treatment-emergent AEs will 
be summarized by treatment group and overall subjects combined. Events reported with 
a partial onset date (e.g., month and year are reported but the day is missing) will be 
considered to be treatment-emergent if it cannot be confirmed that the event onset was 
prior to the first dose of study drug based on the available date entries. 


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Verbatim terms on case report forms will be mapped to preferred terms and system 
organ classes using MedDRA, version 26.0.  
Summaries that are displayed by system organ class and preferred terms will be ordered 
by descending incidence of system organ class and preferred term within each system 
organ class. Summaries displayed by preferred term only will be ordered by descending 
incidence of preferred term. Summaries of the following types will be presented: 
• Overall summary of number of unique TEAEs and treatment-emergent SAEs 
and subject incidence of TEAEs meeting various criteria; 
• Subject incidence of TEAEs by MedDRA system organ class and preferred 
term; 
• Subject incidence of the most frequently-occurring TEAEs (i.e., TEAEs 
occurring in ≥ 10% of the Safety Analysis Set) by MedDRA preferred term; 
• Subject incidence of TEAEs by CTCAE grade, MedDRA system organ class, 
and preferred term; 
• Subject incidence of TEAEs by relationship to study drug, MedDRA system 
organ class, and preferred term;  
• Subject incidence of the most frequently-occurring TEAEs related to study drug 
(i.e., related TEAEs occurring in ≥ 10% of the Safety Analysis Set) by MedDRA 
preferred term; 
• Subject incidence of CTCAE grade 3 or higher TEAEs related to study drug by 
MedDRA system organ class and preferred term; and 
• Subject incidence of SAEs by MedDRA system organ class and preferred term. 
At each level of summarization (e.g., any AE, system organ class, and preferred term), 
subjects experiencing more than one TEAE will be counted only once. In the summary 
of TEAEs by CTCAE grade, subjects will be counted once at the highest grade reported 
at each level of summarization; in the summary of TEAEs by relationship, subjects will 
be counted once at the closest relationship to study drug. Related events include those 
reported as “Related” to study treatment; events considered not related are those 
reported as “Not Related” to study treatment.  
Adverse event data will be presented in data listings by subject, treatment group, and 
event. Serious AEs and AEs leading to discontinuation of the study drug will be 
presented in separate data listings. 
4.5.4 Deaths, Other Serious Adverse Events, and Other Significant Adverse Events 
All deaths during the study, including the post treatment follow-up period, will be listed 
by subject, to include any corresponding details associated with death. Serious AEs and 
other significant AEs, including those that led to discontinuation or interruption of the 
study drug, will be provided in separate subject data listings. 


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4.5.5 Clinical Laboratory Evaluation 
All descriptive summaries of laboratory results will be based on data analyzed by the 
central laboratory and presented in conventional units. All data will be included in by-
subject data listings. Laboratory measurements identified as abnormal (i.e., outside the 
normal range) will also be listed separately by subject, laboratory test, and unit. In 
addition, normal ranges provided by the central laboratory will be presented in a 
separate listing. 
Clinical laboratory measurements, including serum chemistry, hematology, and 
coagulation will be summarized by treatment group and overall subjects combined. 
Descriptive statistics will be presented for observed values and changes from baseline 
at each visit where parameters were scheduled to be collected per the clinical study 
protocol.  
Where applicable, laboratory results will be classified as “low,” “normal,” or “high” 
with respect to the parameter-specific reference ranges (i.e., below the lower limit of 
the normal range, within the normal range, or above the upper limit of the normal 
range). Three-by-three contingency tables will be presented for each laboratory 
parameter to summarize the shift from the baseline category to the worst post-baseline 
measurement, defined as the value numerically farthest outside of the normal range 
across all post-baseline visits through the end of the study. Summary results will include 
the count and percentage of subjects within each shift category and treatment group and 
overall subjects combined. 
The clinical study protocol includes guidance associated with the monitoring and 
interruption of study drug for suspected DILI. Subjects with the following post-baseline 
ALT or AST values will be assessed for the following DILI criteria:  
• ALT or AST >8× ULN 
• ALT or AST >5× ULN for more than 2 weeks: subjects must have confirmed 
elevated values by subsequent repeat testing that shows at least two weeks of 
elevated values.  
• ALT or AST >3× ULN AND total bilirubin >2× ULN OR INR >1.5 
• ALT or AST >3× ULN with the appearance of new onset fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (>5%).  
Subjects qualifying in any of the above treatment-emergent DILI criteria will be 
presented in a data listing.  
4.5.6 Vital Signs, Physical Findings, and Other Observations Related to Safety 
4.5.6.1 
Vital Signs 
Vital sign parameter measurements will be summarized by treatment group and overall 
subjects combined. Descriptive statistics will be presented for results and change from 
baseline at each visit where parameters were scheduled to be collected. 


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Height, body weight and body mass index (BMI) will be summarized by treatment 
group and overall subjects combined.  Body mass index will be calculated as weight 
(kg) / (height at screening [cm] / 100)2. Height at screening, body weight, and BMI will 
be summarized using descriptive statistics for observed measurements and changes 
from baseline (body weight only) at each visit where parameters were scheduled to be 
collected. 
4.5.6.2 
12-Lead Electrocardiogram 
Twelve-Lead ECG interval parameters will be summarized by treatment group and 
overall subjects combined. Descriptive statistics will be presented for observed values 
and changes from baseline at each visit where parameters were scheduled to be 
collected. 
Twelve-lead ECG will be classified by the investigator as “normal,” “abnormal, not 
clinically significant,” or “abnormal, clinically significant.” Three-by-three 
contingency tables will be presented to summarize the shift from the baseline category 
to the worst post-baseline value. Summary results will include the count and percentage 
of subjects within each shift category and treatment group and overall subjects 
combined. 
Prolonged QTc (using corrected QT interval using Fridericia’s formula [QTcF] and 
QTc interval using Bazett’s formula [QTcB]) intervals will be summarized as QTc 
measurements (msec) that are >450, >480, and >500 at each visit where ECG is 
routinely collected per the clinical study protocol. Change from baseline categories will 
also be summarized for measurements that represent a change >30 or >60 relative to 
the baseline value. Summary results will include the percentage of subjects within each 
category and treatment group and for all subjects combined. 
4.5.6.3 
Physical Examination 
Any clinically significant findings from the physical examination assessment will be 
reported on the Medical History form (prior to first dose) or Adverse Events form (post 
first dose). A separate subject listing of physical examination results will not be 
provided. 
4.5.6.4 
Prior and Concomitant Medications 
Medications captured in the Prior AD Therapy and Prior and Concomitant Medications 
will be coded using the WHO Drug Global B3, version March 1, 2023. Medications 
entered on the eCRF will be mapped to ATC drug class (level 2) and preferred name. 
The study phase of each medication will be determined programmatically based on 
medication start and end dates. A prior medication is defined as any medication 
administered prior to the date of the first dose of study drug. A concomitant medication 
is defined as any medication administered on or after the date of the first dose of study 
drug. A medication may be defined as both prior and concomitant. If it cannot be 
determined whether a medication was received prior to the start of study drug dosing 
due to partial or missing medication start and/or end dates, it will be considered a prior 
medication. Likewise, if it cannot be determined whether a medication was received 
after the start of study drug dosing, it will be considered concomitant.  


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Prior AD therapy and concomitant medications will be summarized separately. 
Summarization of Prior AD Therapy is described in Section 4.4.2. The number and 
percentage of subjects receiving any medication will be summarized by treatment group 
and overall subjects combined, as will the number and percentage receiving any 
medication by ATC drug class and preferred name. Subjects reporting use of more than 
one medication at each level of summarization (any medication received, ATC class, 
and preferred name) will be counted only once. ATC class terms will be displayed by 
descending order of incidence, as will preferred names within each ATC class. The 
study phase during which each medication was received (e.g., prior, concomitant, or 
both) will be presented on the listing of prior and concomitant medications. Prior AD 
Therapy will be included on a separate listing. 
A summary of the number and percentage of subjects reporting any concomitant 
emollient use will also be provided; emollient use is considered any reporting of a 
concomitant medications within the ATC drug level 2 of “EMOLLIENTS AND 
PROTECTIVES.” A corresponding listing of concomitant emollient use, to include the 
medication preferred name, will also be provided.  
Subjects who require the use of a rescue medication for their atopic dermatitis within 
the double-blind treatment period will be presented in a separate listing.  
4.5.6.5 
Non-drug Therapies and Surgical Procedures 
The use of any non-drug therapies or surgical procedures will be presented in a subject 
data listing. Subjects who require the use of a rescue procedure for their atopic 
dermatitis within the double-blind treatment period will also be presented in a separate 
listing.  
4.6 
Determination of Sample Size 
No formal sample size calculation has been made. The sample size has been selected to 
provide adequate information on the safety, tolerability, PK, and PD of EP262 over 6 
weeks. 
4.7 
Changes in the Conduct of the Study or Planned Analyses 
Section 15.11 of the clinical study protocol defines the following planned interim 
analysis:  
Given the hypothesis-generating nature of this study, an interim analysis may be 
conducted. The interim analysis would evaluate the effects of EP262 on select PD 
endpoints and safety. 
The decision to conduct an optional interim analysis and the timing of the analysis will 
be documented in the study files prior to conduct of the interim analysis. The SAP will 
be amended if emerging data from the completed interim analysis leads to substantial 
change in the study protocol that has significant impact on the statistical analyses. 
No interim analysis will be conducted for the study. 
Section 15.7 of the clinical study protocol defines the following planned PD analysis:  


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PD analyses will compare placebo and EP262 descriptively. No formal statistical 
testing will be performed. For select PD endpoints, the 90% confidence interval and/or 
nominal p-values will be presented. 
When confidence intervals are presented for PD endpoints, the SAP includes a 95% 
confidence interval across all parameters.  
5. REFERENCE LIST 
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Difference and Responsiveness of the Dermatology Life Quality Index (DLQI): Further 
Data. Dermatology. 2015;230(1):27-33. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--A Simple Practical 
Measure for Routine Clinical Use. Clin Exp Dermatol. 1994;19(3):210-6. 
Hanifin JM, Thurston M, Omoto M, et al. The Eczema Area and Severity Index (EASI): 
Assessment of Reliability in Atopic Dermatitis. EASI Evaluator Group. Exp Dermatol. 
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HHS. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 2017. 
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Howells LM, Chalmers JR, Gran S, et al. Development and Initial Testing of a New 
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Simpson E, Bissonnette R, Eichenfield LF, et al. The Validated Investigator Global 
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Tofte S, Graeber M, Cherill R, et al. Eczema Area and Severity Index (EASI): A New 
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Yosipovitch G, Reaney M, Mastey V, et al. Peak Pruritus Numerical Rating Scale: 
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