Clinical trial NCT04378569
Conditions: Chronic Hand Eczema
Sponsor: Arcutis Biotherapeutics, Inc.
Start date: 2020-04-20; Completion date: 2021-02-24
Enrollment: 230 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will assess the safety and efficacy of ARQ-252 cream in subjects with chronic hand eczema

Detailed description:
This is a Phase 1/2b multiple dose, parallel group, double blind, vehicle-controlled study of the safety and efficacy of ARQ-252 cream in subjects with chronic hand eczema

Arms: arm 1: Active Comparator arm 2: Active Comparator arm 3: Active Comparator arm 4: Placebo Comparator arm 5: Placebo Comparator
Interventions: intervention 1: ARQ-252 cream 0.3% intervention 2: ARQ-252 cream 0.1% intervention 3: ARQ-252 Vehicle Cream
Intervention descriptions: intervention 1: ARQ-252 cream 0.3% intervention 2: ARQ-252 cream 0.1% intervention 3: ARQ-252 Vehicle Cream

Protocol documents:
Prot_000.pdf: 
30 June 2020
Confidential
Page 1 of 72
Protocol ARQ-252-205
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group, Double
Blind, Dose Ranging, Vehicle-Controlled Study of the Safety and
Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream 0.3% in
Subjects with Chronic Hand Eczema
Sponsor:
Arcutis Biotherapeutics, Inc.
2945 Townsgate Road, Suite 110
Westlake Village, CA 91361
Sponsor Representative:
David Berk, MD
Vice President, Clinical Development
Tel: +1 (805) 418-5006 Ext. 711
E-mail: dberk@arcutis.com
Medical Monitor:
Maria Marcano Bozo, MD
One Park Drive, Suite 150
Research Triangle Park, NC 27709
Tel: +1 (512) 686-1256
E-mail: ARCU211360@premier-research.com
IND Number:
140409
Protocol Version:
Amendment 2
Protocol Date:
30 June 2020
GCP Statement
This study is to be performed in full compliance with the protocol, International Conference on Harmonisation Good
Clinical Practices (ICH GCP), and applicable regulatory requirements. All required study documentation will be
archived as required by regulatory authorities.
Confidentiality Statement
This document contains confidential information. It contains proprietary information of Arcutis Biotherapeutics,
Inc. Any viewing or disclosure of such information that is not authorized in writing by Arcutis Biotherapeutics, Inc.
is strictly prohibited. Such information may be used solely for the purpose of reviewing or performing this study.


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Amendment 2
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SITE INVESTIGATOR SIGNATURE PAGE
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group, Double Blind, Dose Ranging,
Vehicle-Controlled Study of the Safety and Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream
0.3% in Subjects with Chronic Hand Eczema
ARQ-252-205
SPONSOR:
Arcutis Biotherapeutics, Inc.
2945 Townsgate Road, Suite 110
Westlake Village, CA 91361
ISSUE DATE:
30 June 2020
I have read this protocol, including all appendices, and I agree that it contains all necessary
details for me and my staff to conduct this study as described. I will conduct this study as
outlined herein, in accordance with the current International Conference on Harmonisation Good
Clinical Practices (ICH GCPs) and applicable local and regional regulations.
I will provide all study personnel under my supervision copies of the protocol and access to all
information provided by Arcutis Biotherapeutics, Inc. I will discuss the material with them to
ensure that they are fully informed about ARQ-252 and the study.
I agree that I or my designee will completely inform all subjects in this study concerning the
pertinent details and purpose of the study prior to their agreement to participate in the study in
accordance with cGCPs and regulatory authority requirements. I will be responsible for
maintaining each subject’s consent form in the study file and providing each subject with a
signed copy of the consent form.
I agree to maintain the confidentiality of all information received or developed in connection
with this protocol.
Investigational Site Name: __________________________________
Print Investigator Name:
__________________________________
Investigator Signature: __________________________________ Date: _______________


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SUMMARY OF CHANGES
The following sections have been changed in Amendment 2 of the ARQ-252-205 protocol:
Section
Summary of Changes
1.3
Schedule of Visits and
Assessments (Cohort 2)
Clarified language in the footnote for IP dispensing.
2.4.2
Risks and/or Benefits to
Subjects
Added the potential risks of ARQ-252 cream.
4.2
Number of Sites and
Subjects
Clarified language regarding the replacement of subjects.
4.7.2
Exclusion Criteria
Clarified exclusion criterion for positive patch test with
continued exposure to allergen.
4.8
Removal of Subjects
from Investigational
Product
Updated the reasons for discontinuation of IP.
4.10
Treatment Stopping
Rules
Added additional criteria for treatment discontinuation and
clarified existing criteria.
5.1.1
Screening
Added review of allergies and/or contact dermatitis to the
medical history assessment at the Screening Visit.
5.1.2
Contraception
Requirements
Added statements regarding nonclinical research on fetal
development and the requirement to adhere to the pregnancy
testing and/or contraception requirements of the protocol.
Editorial changes made throughout to improve accuracy or readability


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TABLE OF CONTENTS
1.
PROTOCOL SUMMARY ................................................................................................. 10
Synopsis ......................................................................................................................... 10
Study Schema................................................................................................................ 18
Schedule of Visits and Assessments ............................................................................ 20
2.
INTRODUCTION............................................................................................................... 24
Background................................................................................................................... 24
Nonclinical Safety Summary ....................................................................................... 25
Clinical Studies ............................................................................................................. 26
Oral Administration: Phase 1 ...................................................................................26
Oral Administration: Phase 2 ...................................................................................27
Additional Studies....................................................................................................30
Rationale for Development.......................................................................................... 31
Dose Selection..........................................................................................................31
Risks and/or Benefits to Subjects.............................................................................32
3.
STUDY ENDPOINTS AND OBJECTIVES..................................................................... 32
Study Objectives........................................................................................................... 32
Primary Objectives...................................................................................................32
Study Endpoints............................................................................................................ 33
Primary Endpoints....................................................................................................33
Secondary Endpoints................................................................................................33
Exploratory Endpoints..............................................................................................34
4.
INVESTIGATIONAL PLAN ............................................................................................ 34
Overall Study Design and Plan ................................................................................... 34
Number of Sites and Subjects...................................................................................... 34
Subject Participation.................................................................................................... 35
Randomization.............................................................................................................. 35
Numbering of Subjects................................................................................................. 36
Blinding ......................................................................................................................... 36
Breaking Treatment Codes.......................................................................................36
Selection of Study Population...................................................................................... 37
Inclusion Criteria......................................................................................................37
Exclusion Criteria.....................................................................................................38
Removal of Subjects from Investigational Product................................................... 39
Removal of Subjects from the Study .......................................................................... 40
Treatment Stopping Rules........................................................................................... 40


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Study Restrictions......................................................................................................... 41
Prohibitions and Concomitant Therapy....................................................................41
Treatment...................................................................................................................... 42
Investigational Product Supplies, Packaging and Labeling .....................................42
Treatment Administration ........................................................................................43
Treatment Compliance .............................................................................................43
5.
STUDY PROCEDURES .................................................................................................... 44
Safety Assessments ....................................................................................................... 44
Screening..................................................................................................................44
Contraception Requirements....................................................................................45
Physical Examination...............................................................................................46
Vital Signs, Height and Weight................................................................................46
12-lead ECGs ...........................................................................................................46
Laboratory Tests.......................................................................................................47
Local Tolerability Assessment.................................................................................48
Adverse Events.........................................................................................................49
Efficacy Evaluations..................................................................................................... 49
Investigator’s Global Assessment (IGA) .................................................................49
Body Surface Area (BSA)........................................................................................51
Worst Itch Numerical Rating Scale (WI-NRS)........................................................51
NRS-Pain Scale........................................................................................................51
HECSI ......................................................................................................................52
Quality of Life in Hand Eczema Questionnaire.......................................................53
Nail Dystrophy Assessment .....................................................................................53
Other Evaluations......................................................................................................... 53
Pharmacokinetics Assessment..................................................................................53
Medical Photography ...............................................................................................54
Final Study Visit – End of Study................................................................................. 54
Early Termination Visit............................................................................................... 54
Unscheduled Visit......................................................................................................... 54
Adverse Events.............................................................................................................. 55
Adverse Event Definition.........................................................................................55
Serious Adverse Event Definition............................................................................55
Suspected Unexpected Serious Adverse Reaction (SUSAR) ..................................56
Safety Review with Subject .....................................................................................57
Adverse Event Reporting .........................................................................................57
Reporting Pregnancy.................................................................................................... 58
6.
DATA ANALYSIS.............................................................................................................. 59
Statistical Methods ....................................................................................................... 59
Determination of Sample Size..................................................................................59
Subjects to Analyze..................................................................................................60


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Interim Analysis .......................................................................................................60
Background and Demographic Characteristics........................................................60
Study Disposition.....................................................................................................60
Protocol Deviations and Eligibility Deviations........................................................60
Investigational Product Compliance ........................................................................61
Efficacy Evaluation ...................................................................................................... 61
Primary Efficacy Endpoint.......................................................................................61
Secondary Endpoints................................................................................................61
Exploratory Endpoints..............................................................................................62
Safety Analysis.............................................................................................................. 62
Adverse Events.........................................................................................................62
Local Tolerance Assessment....................................................................................63
Medical History and Physical Examinations ...........................................................63
Clinical Laboratory Results and Vital Signs............................................................63
Prior and Concomitant Medications.........................................................................63
Pharmacokinetic Analysis............................................................................................ 63
7.
STUDY ADMINISTRATION............................................................................................ 63
Ethics ............................................................................................................................. 63
Ethics Review Board................................................................................................63
Ethical Conduct of the Study ...................................................................................64
Subject Information and Consent.............................................................................64
Study Completion and Termination ........................................................................... 64
Study Completion.....................................................................................................64
Study Termination....................................................................................................64
Study Monitoring.......................................................................................................... 65
Data Quality Assurance ............................................................................................... 65
Data Handling and Record Keeping........................................................................... 65
Protocol Amendments and Deviations........................................................................ 66
Confidentiality and Privacy......................................................................................... 66
Conflict of Interest........................................................................................................ 67
Report Format .............................................................................................................. 67
Publication Policy......................................................................................................... 67
8.
REFERENCES.................................................................................................................... 68


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LIST OF TABLES
Table 1.
Proportion of Patients Reaching ACR20/50/70 and Statistical Check
(CMH-FAS-NRI) after 12-week Administration in a Multicenter,
Randomized, Double-blind, Placebo-controlled Phase II Study Evaluating
the Efficacy and Safety of SHR0302 Tables in Patients with Moderate to
Severe Active Rheumatoid Arthritis......................................................................28
Table 2.
Excluded Medications and Treatments..................................................................41
Table 3.
Laboratory Tests ....................................................................................................47
LIST OF FIGURES
Figure 1.
Contraception Requirements for Female Subjects.................................................46
LIST OF APPENDICES
Appendix 1.
Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)................................70


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ABBREVIATIONS
Abbreviation
Definition
ACR20
American College of Rheumatology 20% improvement in rheumatoid
arthritis score
ACR50
American College of Rheumatology 50% improvement in rheumatoid
arthritis score
ACR70
American College of Rheumatology 70% improvement in rheumatoid
arthritis score
AE
Adverse Event
AUC
Area Under the Curve
BID
Twice Daily ("bis in die")
BSA
Body Surface Area
Cmax
Maximum Concentration
Cm
Centimeter
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
DNA
Deoxyribonucleic Acid
EC
Ethics Committee
ECG
Electrocardiogram
FDA
U.S. Food and Drug Administration
FOCBP
Female of Childbearing Potential
FSH
Follicle-Stimulating Hormone
GCP
Good Clinical Practices
Hr
Hour
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
ID
Identification
IGA
Investigator’s Global Assessment
IL
Interleukin
IND
Investigational New Drug
IP
Investigational Product
IRB
Institutional Review Board
ITT
Intent to Treat
IRT
Interactive Response Technology


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Abbreviation
Definition
Kg
Kilogram
µg
Microgram
MAD
Multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
Mg
Milligram
Min
Minute
mL
Milliliter
NCI
National Cancer Institute
NIH
National Institutes of Health
NOAEL
No Observed Adverse Effect Level
Ng
Nanogram
NRS
Numerical Rating Scale
P-450
Cytochrome P450
PDE-4
Phosphodiesterase 4
PI
Principal Investigator
PK
Pharmacokinetics
QD
Once Daily ("quaque die")
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SUSAR
Suspected Unexpected Serious Adverse Reaction
TCPS
Tri-Council Policy Statement
TEAE
Treatment Emergent Adverse Event
Tmax
Time to Reach Maximum Concentration
US
United States
WI-NRS
Worst Itch – Numeric Rating Score


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1.
PROTOCOL SUMMARY
Synopsis
Protocol Title:
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group,
Double Blind, Dose Ranging, Vehicle-Controlled Study of the Safety
and Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream 0.3% in
Subjects with Chronic Hand Eczema
Clinical Indication:
Chronic Hand Eczema (CHE)
Investigational
Product:
ARQ-252 cream will be supplied as ARQ-252 cream 0.1%
(only applicable in Cohort 2) and ARQ-252 cream 0.3%.
Matching vehicle cream (only applicable in Cohort 2) will contain
only excipients of ARQ-252 cream.
The active ingredient in ARQ-252 cream is SHR0302, a selective
JAK1 inhibitor.
Study Design:
ARQ-252-205 is a Phase 1/2b, Multiple Dose and 12-week, parallel
group, double blind, vehicle-controlled study of the safety and
efficacy of ARQ-252 cream 0.1% and ARQ-252 cream 0.3% in
subjects with chronic hand eczema.
There are 2 cohorts of subjects.
•
Cohort 1 is a multiple dose cohort in which subjects with chronic
hand eczema will be assigned to ARQ-252 cream
0.3% QD x 2 weeks to be applied to both hands (approximately
4% of BSA). PK and tolerability will be evaluated.
•
Cohort 2 is a parallel group, double blind, vehicle-controlled
cohort in which subjects with chronic hand eczema will be
randomized to ARQ-252 cream 0.3% QD, ARQ-252 cream
0.3% BID, ARQ-252 cream 0.1% QD, vehicle cream BID or
vehicle cream QD x 12 weeks to be applied to both hands
(approximately 4% of BSA). Safety and efficacy will be
evaluated.
Study Objectives:
The objectives of this study are as follows:
Phase 1 (Cohort 1)
•
To assess the safety, tolerability and PK of QD application of
ARQ-252 0.3% to both hands for 2 weeks in 6 subjects with
chronic hand eczema (Cohort 1)
Phase 2b (Cohort 2)
•
To assess the safety and efficacy of ARQ-252 cream 0.1% QD and
ARQ-252 cream 0.3% QD and BID, vs vehicle applied QD and
BID for 12 weeks to subjects with chronic hand eczema (Cohort 2)
Study Sites:
Approximately 45 sites in the United States, Canada and Australia.


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Study Population:
For both Cohorts, subjects will be male and female adults (≥18 years
of age), with chronic hand eczema, and an Investigator’s Global
Assessment (IGA) of disease severity of at least Mild (‘2’) at
Baseline. In Cohort 2, subjects with IGA of ‘Mild’ will be limited to
20% of total enrollment, and subjects with IGA of ‘Severe’ will also
be limited to 20% of total enrollment.
•
Cohort 1 will include approximately 6 evaluable subjects,
assigned to ARQ-252 cream 0.3% QD
•
Cohort 2 will include approximately 215 subjects, randomized
2:2:1:1:1 to ARQ-252 cream 0.3% QD : ARQ-252 cream
0.3% BID : ARQ-252 cream 0.1% QD : vehicle cream BID:
vehicle cream QD
Duration of
Participation for
Subjects:
Cohort 1: Screening (up to 4 weeks), Treatment phase (2 weeks),
and follow-up (1 week post-treatment completion) for a total of
7 weeks
Cohort 2: Screening (up to 4 weeks), Treatment phase (12 weeks),
and follow-up (1 week post-treatment completion); for a total of
17 weeks
Inclusion Criteria:
1. Participants legally competent to sign and give informed consent.
2. Males and females 18 years of age and older (inclusive) at the
time of consent.
3. Clinical diagnosis of chronic hand eczema, defined as hand
eczema persistent for more than 3 months, or returned twice or
more within the last 12 months (Diepgen 2009). Generally stable
disease for 6 weeks. Both irritant and non-irritant etiologic forms
are allowed. All morphologic types are allowed,
e.g., vesicular/dyshidrotic, hyperkeratotic, nummular, and other
types.
4. An Investigator’s Global Assessment of disease severity (IGA) of
at least Mild (‘2’) at Baseline (Visit 2). (In Cohort 2, subjects with
IGA of ‘Mild’ will be limited to 20% of total enrollment, and
subjects with IGA of ‘Severe’ subjects will also be limited to 20%
of total enrollment).
5. Chronic hand eczema involving at least 0.3% body surface area
total (i.e., approximately a third of one handprint) lesions on both
hands added together at Baseline (Visit 2).
6. Female subjects of childbearing potential (FOCBP) must have a
negative serum pregnancy test at Screening and negative urine
pregnancy test at Baseline (Visit 2). For FOCBP involved in any
sexual intercourse that could lead to pregnancy: the subject must
agree to use a highly effective contraceptive method for at least
4 weeks prior to Day 1. Additionally, from Day 1 until at least
4 weeks after the last investigational product administration, these


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subjects must agree to use at least 1 highly effective contraceptive
method in addition to 1 barrier method according to Contraception
Requirements (Figure 1).
7. Females of non-childbearing potential must either be post-
menopausal with spontaneous amenorrhea for at least 12 months
(post-menopausal status will be confirmed with FSH testing) or
have undergone surgical sterilization (permanent sterilization
methods include hysterectomy, bilateral oophorectomy,
hysteroscopic sterilization or bilateral salpingectomy) according to
Contraception Requirements (Figure 1).
8. Males, if engaging in sexual intercourse with a female who is
pregnant or a female of childbearing potential, must agree to use a
condom every time during the study and every time subsequently
until 4 weeks after the last investigational product administration.
9. Males must agree not to donate sperm from the first dose of
investigational product until 4 weeks after the last investigational
product administration.
10. Subjects in good health as judged by the Investigator, based on
medical history, physical examination, 12-lead electrocardiogram
(ECG), serum chemistry labs, hematology values, and urinalysis.
11. Subjects are considered reliable and capable of adhering to the
Protocol and visit schedule, according to the judgment of the
Investigator.
Exclusion Criteria:
1. Concurrent skin diseases on the hands which, in the opinion of the
Investigator, could confound the study (e.g., tinnea manuum).
2. Active skin diseases not on the hands such as atopic dermatitis or
psoriasis requiring medical treatment that could significantly
affect hand eczema, in the Investigator’s opinion.
3. Subjects with any presence or history of psoriasis.
4. History of a positive patch test with continued exposure to
allergen. If, in the opinion of the Investigator, there is any
suspected allergic hand eczema with continued exposure to
allergen, subject must undergo diagnostic patch testing to
determine if they meet entry criteria prior to Baseline (Visit 2).
5. Subjects who cannot discontinue systemic and/or topical therapies
for the treatment of chronic hand eczema prior to Baseline
(Visit 2) and during the study according to Excluded Medications
and Treatments (Table 2), (i.e., immunosuppressive drugs,
immunomodulating drugs, retinoids, or corticosteroids).
6. Psoralen ultraviolet A (PUVA) or ultraviolet B (UVB) therapy on
the hands within 4 weeks prior to Baseline (Visit 2).


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7. Cutaneously applied treatment with immunomodulators
(e.g., phosphodiesterase-4 (PDE-4) inhibitors, pimecrolimus,
tacrolimus), topical urea moisturizers, topical antibiotics, or low
or mid potency topical corticosteroids on the hands or elsewhere
within 1 week prior to Baseline (Visit 2). Cutaneously applied
treatment with high potency topical corticosteroids on the hands
or elsewhere within 2 weeks prior to Baseline (Visit 2).
8. Subjects that have significant active systemic or localized
infection, including known actively infected eczema or have had
any infection that required oral or intravenous administration of
antibiotics, antifungal or antiviral agents within 2 weeks prior to
Baseline (Visit 2).
9. Other cutaneously applied therapy on the hands (except for the use
of subject's own non-urea and non-salicylic acid emollients)
within 1 week prior to Baseline (Visit 2).
10. Subjects who are unwilling to refrain from using a tanning bed or
other LEDs as well as outdoor tanning or excessive sun exposure
for 4 weeks prior to Baseline (Visit 2) and during the study.
11. Subjects with a history of chronic alcohol or drug abuse within
6 months prior to Baseline (Visit 2).
12. Current or a history of cancer within 5 years with the exception of
fully treated skin basal cell carcinoma, cutaneous squamous cell
carcinoma or carcinoma in situ of the cervix.
13. Subjects that have received live vaccine therapy less than 4 weeks
prior to Baseline (Visit 2), immunosuppressive drugs less than
4 weeks prior to Baseline (Visit 2), or have known infection with
mycobacterium tuberculosis, hepatitis B or C, or HIV, or have a
diagnosis of an immunodeficiency disorder.
14. Subject had a major surgery within 4 weeks prior to Baseline
(Visit 2) or has a major surgery planned during the study.
15. Known or suspected:
•
severe renal insufficiency or severe hepatic disorders
•
hypersensitivity to component(s) of the investigational product
which include SHR0302, butylated hydroxytoluene (BHT),
benzyl alcohol, dimethyl sulfoxide, cyclomethicone,
dimethicone (350 cst), ST-Elastomer 10, water, propylene
glycol, polyethylene glycol 200, Pemulen TR1, Carbopol
974P, ethylenediaminetetraacetic acid, trolamine and
D-limonene.
16. Pregnant or lactating women or women planning to become
pregnant during the study and / or within 28 days following the
last dose of investigational product.


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17. Subjects who cannot discontinue the use of strong systemic
Cytochrome P-450 3A4 inducers e.g., efavirenz, nevirapine,
glucocorticoids, barbiturates (including phenobarbital), phenytoin,
rifampin and carbamazepine for 2 weeks prior to Baseline
(Visit 2) and during the study period.
18. Subjects who cannot discontinue the use of strong systemic
Cytochrome P-450 3A4 inhibitors e.g., indinavir, nelfinavir,
ritonavir, clarithromycin, itraconazole, ketoconazole, fluconazole,
nefazodone, saquinavir, suboxone and telithromycin for 2 weeks
prior to Baseline (Visit 2) and during the study period.
19. Subjects with any serious medical condition or clinically
significant laboratory, ECG, vital signs or physical examination
abnormality that would prevent study participation or place the
subject at significant risk, as judged by the Investigator.
Key Assessments:
Phase 1 (Cohort 1):
•
Safety will be monitored through application site assessments,
safety labs, AEs, ECGs, physical examinations, and vital
signs.
•
Serial PK sampling will be performed on Day 1 (1, 2, 4, 6,
and 24 hours post-dose administration), and at Day 15
(pre-dose and 1, 2, 4, 6, and 24 hours post-dose
administration). For 24-hour timepoints, subjects return to the
clinic on the following day within 2 hours of the IP application
time from the previous day for PK plasma sample collection.
A pre-dose/trough PK sample will be taken at Day 8.
Phase 2b (Cohort 2):
•
Safety will be monitored through application site assessments,
safety labs, AEs, ECGs, physical examinations, and vital
signs.
•
Efficacy will be evaluated through IGA, HECSI, WI-NRS
Pruritus, NRS Pain, Nail Dystrophy Assessments and
QOLHEQ
•
PK will be evaluated through trough/pre-dose sampling at
Baseline, Day 29, and Day 85.
Study Endpoints:
Phase 1 (Cohort 1):
•
Safety, as measured by the incidence and severity of adverse
events, changes in laboratory parameters, tolerability, and
pharmacokinetics.
Phase 2b (Cohort 2):
The primary endpoint of Cohort 2 is:
•
The rate of an IGA score of ‘clear’ or ‘almost clear’ at
Week 12


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Phase 2b (Cohort 2):
The secondary endpoints of Cohort 2 are:
•
The rate of achievement of IGA of ‘clear’ or ‘almost clear’
PLUS at least a 2-point improvement from Baseline at
Weeks 2, 4, 8 and 12
•
The rate of achievement of at least a 2-point improvement
from Baseline at Weeks 2, 4, 8 and 12
•
Achievement of IGA of ‘clear’ or ‘almost clear’ at Weeks 2, 4,
and 8
•
Time to IGA of ‘clear’ or ‘almost clear’
•
Change in IGA score at Weeks 2, 4, 8, and 12 as compared to
Baseline
•
Change in WI-NRS pruritus score at 2 weeks, 4 weeks,
8 weeks, and 12 weeks compared to Baseline
•
The rate of achievement of ≥4-point reduction from Baseline
in WI-NRS pruritus score at 2 weeks, 4 weeks, 8 weeks, and
12 weeks in subjects with Baseline WI-NRS pruritus score of
at least 4
•
Time to the first achievement of ≥4-point reduction from
Baseline in WI-NRS pruritus score in subjects with Baseline
WI-NRS pruritus score of at least 4
•
Percent change in HECSI (Hand Eczema Severity Index) score
at Weeks 2, 4, 8, and 12 compared to Baseline
•
Change in NRS Pain score at 2 weeks, 4 weeks, 8 weeks, and
12 weeks compared to Baseline
•
The rate of achievement of ≥4-point reduction from Baseline
in Pain NRS score at 2 weeks, 4 weeks, 8 weeks, and
12 weeks in subjects with Baseline Pain NRS score of at least
4
•
Time to the first achievement of ≥4-point reduction from
Baseline in Pain NRS score in subjects with Baseline Pain
NRS score of at least 4
•
Change from Baseline in overall Quality of Life in Hand
Eczema Questionnaire (QOLHEQ) score at each visit
•
Percent BSA affected by disease and % change from baseline
in BSA affected by disease at baseline, 2 weeks, 4 weeks,
8 weeks, and 12 weeks.
The exploratory endpoint of Cohort 2 is:
•
Change from Baseline in Nail Dystrophy at each visit


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Power and Sample
Size:
Cohort 1 will include approximately 6 evaluable subjects, which is
deemed adequate for the purpose of evaluating safety and PK prior to
Cohort 2.
There are approximately 215 subjects planned for Cohort 2.
Approximately 61 subjects will receive ARQ-252 cream 0.3% QD,
approximately 61 subjects will receive ARQ-252 cream 0.3% BID,
approximately 31 subjects will receive ARQ-252 cream 0.1% QD,
approximately 31 subjects will receive matching vehicle cream QD,
and approximately 31 subjects will receive vehicle cream BID.
The randomization scheme will be 2:2:1:1:1 between these
5 treatment groups, stratified by study site and IGA at Baseline.
The primary statistical comparisons will be to assess the ARQ-252
cream 0.3% BID group versus the vehicle BID group, to assess the
ARQ-252 cream 0.3% QD group versus the vehicle QD group, and to
assess the ARQ-252 cream 0.1% QD group versus the vehicle QD
group.
A sample size of 55 per active arm and 28 per vehicle arm will
provide approximately 85% power at the 2-sided 5% significance
level to detect a difference in the percent of subjects with IGA clear or
almost clear at Week 12; for each ARQ-252-treated group versus
vehicle group within the same daily dosing frequency, assuming an
active treatment response rate of 45% and a vehicle response rate of
15%, with a two-sided α = 0.1. This is based on a 2-group X2 test of
equal proportions (without continuity correction). With a 10%
dropout rate, the sample size for the study is increased to 61 subjects
per active arm and 31 subjects per vehicle arm (215 subjects total).
The primary statistical comparisons and evaluation of the secondary
endpoints will not be adjusted for multiplicity.
Statistical Analysis:
Descriptive statistics will be presented for the study endpoints. This
includes the number and percentage of subjects for binary
endpoints/categorical data, and mean, SD, median, minimum, and
maximum for continuous data.
The primary endpoint in Cohort 2 of ‘IGA clear or almost clear at
Week 12’ will be analyzed using a Cochran-Mantel-Haenszel test
stratified by study site and IGA at Baseline. The analysis will be
performed on the Intention-to-Treat (ITT) population and missing
data will be imputed using multiple imputation.
Continuous secondary endpoints measured in Cohort 2 will be
analyzed using Analysis of Covariance with treatment and
stratification factors as independent variables. The ITT population
will be used. Binary secondary endpoints will be analyzed similarly
to the primary endpoint.


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All subjects who are randomized and receive at least one confirmed
dose of investigational product will be included in the safety
population.
Adverse events (AEs) will be summarized within each cohort by
preferred term, system organ class, and treatment group (Cohort 2
only) for all treatment-emergent AEs, serious AEs, related AEs,
AEs leading to withdrawal from investigational product.
Safety laboratory parameters and vital signs will be summarized at
each visit using descriptive statistics or frequencies and percentages,
as appropriate. Changes from Baseline in laboratory values and vital
signs will also be summarized by visit. In addition, changes from
Baseline in weight and laboratory values will be summarized using
shift tables. These summaries will be tabulated by treatment group
for Cohort 2.
All subjects who are enrolled and receive at least one application of
investigational product and have sufficient pharmacokinetic
assessments will be included in the pharmacokinetic population
(Cohorts 1 and 2). When possible, the exposure to SHR0302 will be
calculated based on plasma concentrations versus time profile data.


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Study Schema
Phase 1 (Cohort 1)
Screening
N = 6 Enrolled
Baseline
Treatment Day 1
ARQ-252 0.3% QD (once daily)
Follow Up Period / Visit
2 Week Treatment Period, PK Assessments and Clinic Visits
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group, Double Blind, Dose
Ranging, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-252 Cream
0.1% and ARQ-252 Cream 0.3% in Subjects with Chronic Hand Eczema
Phase 1/Cohort 1
Approximately 6 subjects with chronic hand eczema will receive ARQ-252 0.3%
cream QD (once daily)


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Phase 2b (Cohort 2)
ARQ-252
0.1% QD
(once daily)
Vehicle Cream
QD
(once daily)
12 Week Treatment Period and Clinic Visits
ARQ-252
0.3% QD
(once daily)
ARQ-252
0.3% BID
(twice daily)
Follow Up Period / Visit
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group, Double Blind, Dose Ranging,
Vehicle-Controlled Study of the Safety and Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream
0.3% in Subjects with Chronic Hand Eczema
Phase 2b/Cohort 2
Approximately 215 subjects with chronic hand eczema will be randomized to receive either:
•
ARQ-252 0.3% cream QD (once daily) N=61
•
ARQ-252 0.3% cream BID (twice daily) N=61
•
ARQ-252 0.1% cream QD (once daily) N=31
•
Vehicle cream QD (once daily) N=31
•
Vehicle cream BID (twice daily) N=31
The randomization scheme will be 2:2:1:1:1 between these 5 treatment groups, stratified by study site,
and IGA at Baseline.
Screening
N = 215 Enrolled
Baseline
Randomization and Treatment Day 1
Vehicle Cream
BID
(twice daily)


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Schedule of Visits and Assessments
A. Cohort 1 (Phase 1)
Study Procedure
Screening
Baseline
Day 1
PK
Collection
Day 2
Day 8
Week 2
Day 15
PK
Collection
Day 16
Week 3
Day 22
Visit
1
2
3
4
5
6
7
Visit Window
-4 Weeks
+/- 2 hrs
+/-1 day
+/- 1 day
+/- 2 hrs
+/- 3 days
Informed Consent
X
Demographics
X
Medical and Surgical History
X
Physical examinationa
X
X
X
X
X
I/E criteria
X
X
Hematology, Serum
Chemistries, Urine Analysis,
TSH, T4b
X
X
X
X
X
Vital signs, weight, heightc
X
X
X
X
X
Local tolerability assessmentd
X
X
X
BSA, IGA, HECSIe
X
X
X
WI-NRS, NRS Painf
X
Completed daily from Day 1-Day 15
Urine pregnancy testg
X
X
X
X
Serum pregnancy testg
X
Follicle-Stimulating Hormone
(FSH)h
X
Resting 12-lead ECG
X
X
PK samplingi
X
X
X
X
X
IP application in clinicj
X
X
X
Dispense IP
X
Weigh investigational product
containerk
X
X
Dispense/review diary
X
X
X
Adverse event assessmentl
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X


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Footnotes from above table:
a Limited physical examination: skin, lungs, and heart only.
b All samples listed to be collected at Visits 1, 2, 4, 5, and 7. If Baseline visit occurs within 14 days of Screening, the
Screening lab results may be utilized. Refer to Table 3.
c Height to be measured only at Visit 2 (Day 1). Weight will be collected at Baseline, Visits 4, 5 and 7.
d Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of skin irritation
(Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s ‘0-3’
burning/stinging assessment. Note for investigator tolerability assessments: reactions at the site of IP
application, which may occur post-Baseline, should be differentiated from the preexisting inflammation
associated with the subject’s chronic hand eczema.
e BSA will be measured as the affected BSA for each side of each hand. Affected areas of the lateral aspects of the
fingers and hands should be assigned to the palmar surface. IGA will be a 5-point scale ranging from clear (0) to
severe (4). IGA should be completed prior to other physician assessments and by the same Evaluator at each
study visit. HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and
the extent of the lesions on each of 5 distinct hand anatomic areas by use of standard scales. The total HECSI score
is based on a 4-point clinical sign severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating
the different affected hand anatomic area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area).
f Subjects will complete the WI-NRS pruritis assessment and NRS Pain assessment in the clinic during screening and
then daily at home from the Baseline/Day 1 visit through the Day 15 visit.
g A serum pregnancy test will be administered to all females of child-bearing potential at Screening. A urine
pregnancy test will be administered at Visits 2, 4, 5, and 7 to all females of childbearing potential. A negative result
is required for continued participation in the study, and results must be available prior to dispensing of
investigational product.
h FSH will be performed (if indicated) at Screening to confirm post-menopausal status.
i On the first day of dosing (Day 1), PK samples will be collected at 1, 2, 4, 6 (all +/- 10 mins) and 24 hours post-dose
administration (Day 2, +/- 2 hours). On Day 15 (last dose application), PK samples will be collected pre-dose, 1, 2,
4, 6, (all +/- 10 mins) and 24 hours post dose administration (Day 16, +/- 2 hours). For 24-hour timepoints, subjects
return to the clinic on the following day within 2 hours of the IP application time from the previous day for pre-dose
PK plasma sample. A pre-dose PK sample will be taken at Day 8.
j Clinic personnel will apply assigned IP on Visits 2, 4 and 5 (Baseline, Day 8 and Day 15). Every tube should be
weighed before and after IP application and weights recorded. For the 24-hour PK sampling timepoint the
application of investigational product should occur after the PK sample has been collected.
k Subject should return with investigational product kit at each Visit. Every tube should be weighed before and after
use and weights recorded when dispensed and returned.
l Any emergent AEs will be followed in the clinic for up to 1 month at the Investigator’s discretion until resolved or
otherwise judged as clinically stable


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B. Cohort 2 (Phase 2b)
Study Procedure
Screen
Baseline
Day 1
Wk 2
Day 15
Wk 4
Day 29
Wk 8
Day 57
Wk 12
Day 85
Wk 13
Day 92
Visit
1
2
3
4
5
6
7
Visit Window
-4 weeks
+/- 3 days
+/- 5 days
+/- 5 days
+/- 7 days
+/- 3 days
Informed consent
X
Demographics
X
Medical and surgical history
X
Physical examinationa
X
X
X
Vital signs, height, weightb
X
X
X
X
X
X
X
I/E criteria
X
X
Randomization
X
Hematology, Serum Chemistries,
UA, TSH/T4c
X
X
X
X
X
Resting 12-lead ECG
X
X
X
BSA, IGA, HECSId
X
X
X
X
X
X
X
NRS pain, WI-NRSe
X
Completed daily from Day 1 to Week 13 Visit
QOLHEQe
X
X
X
X
X
X
X
Nail dystrophy assessmentf
X
X
X
X
X
X
Local Tolerability Assessmentsg
X
X
X
X
X
Optional Photographyh
X
X
X
X
X
X
Urine pregnancy testi
X
X
X
X
X
Serum pregnancy testi
X
Follicle-Stimulating Hormone
(FSH)j
X
PK samplingk
X
X
X
IP application/Subject training in
clinicl
X
X
X
X
X
Dispense IP kitm
X
X
X
X
X
Dispense/review diary
X
X
X
X
X
Weigh IP tubesn
X
X
X
X
X
Compliance calculationo
X
X
X
X
X
Adverse event assessmentp
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X


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Footnotes from above table:
a Limited physical examination: skin, lungs, and heart only
b Height will be collected at Visit 2 (Baseline/Day 1) only. Weight will be collected at Baseline, Weeks 4, 8 and 12.
c If Baseline visit occurs within 14 days of Screening, the Screening lab results may be utilized.
d BSA will be measured as the affected BSA for each side of each hand. Affected areas of the lateral aspects of the
fingers and hands should be assigned to the palmar surface. IGA will be a 5-point scale ranging from clear (0) to
severe (4). IGA should be completed prior to other physician assessments and by the same Evaluator at each
study visit. HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and
the extent of the lesions on each of 5 distinct hand anatomic areas by use of standard scales. The total HECSI score
is based on a 4-point clinical sign severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating
the different affected hand anatomic area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area).
e Subjects will complete the WI-NRS pruritis assessment and NRS Pain assessment in the clinic during Screening and
then daily at home from the Baseline/Day 1 visit until the Week 13 visit. QOLHEQ = Quality of Life in Hand
Eczema Questionnaire will be completed at each visit.
f Assessment of nail dystrophy including Baseline identification of the nail with the worst dystrophy and
measurement of the millimeters of normal appearing nail distal to the cuticle post Baseline. Sites participating in
optional photography will obtain photos of nail with the worst dystrophy at Baseline/Day 1 and at subsequent visits.
See Section 5.2.7 for details.
g Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of skin irritation
(Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s ‘0-3’
burning/stinging assessment. Note for investigator tolerability assessments: reactions at the site of IP
application, which may occur post-Baseline, should be differentiated from the preexisting inflammation
associated with the subject’s chronic hand eczema.
h Photography will be performed at selected investigational sites. Photography will be optional. All efforts will be
made to de-identify the subjects. Sites participating in optional photography will obtain photos of nail with the worst
dystrophy at Baseline/Day 1 and at subsequent visits.
i A serum pregnancy test will be administered to all females of childbearing potential at Screening. A urine pregnancy
test will be administered at Baseline, Weeks 4, 8, 12 and 13. A negative result is required for continued participation
in the study, and results must be available prior to dispensing of investigational product.
j FSH will be performed (if indicated) at Screening to confirm post-menopausal status.
k PK assessments will be collected from all subjects at Days 1, 29 and 85. The draws will be pre-dose IP application
in the clinic.
l Subjects to apply assigned IP in clinic at these visits. The time of application will be documented.
m Kits will be dispensed at Baseline, Weeks 2, 4 and 8. Dispensing at Week 12 requires approval from the Medical
Monitor. See IP Handling Manual for details.
n Each IP tube will be weighed prior to dispensing at the Baseline visit and at each follow-up clinic visit according to
the Schedule of Visits and Assessments. When IP is applied in the clinic, the IP tube will be weighed before and
after IP application. See IP Handling Manual for details.
o Compliance calculation is described in the IP Handling Manual.
p Any emergent AEs will be followed in the clinic for up to one month at the Investigator’s discretion until resolved or
otherwise judged as clinically stable.


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2.
INTRODUCTION
Background
Chronic hand eczema is a common condition which occurs in different forms. Chronic hand
eczema may significantly impact quality of life and cause significant costs, e.g., through inability
of patients to work. There is considerable unmet medical need for new therapies for hand eczema
since few treatments are available and/or approved specifically for hand eczema
(e.g., no FDA-approved therapies) and treatment is often unsatisfactory (Diepgen 2009).
Janus kinases (JAKs) are a family of intracellular nonreceptor tyrosine kinases that transduce
cytokine-mediated signals via the JAK-signal transducer and activator of transcription (STAT)
pathway and have a plethora of effects on the immune system, inflammation, and hematopoiesis.
In humans, the JAK family includes JAK1, JAK2, JAK3, and tyrosine kinase 2 (Tyk2). JAK1 is
a human tyrosine kinase which plays a critical role in initiating responses to multiple major
cytokines. It interacts with the common gamma chain of type I cytokine receptors to elicit signals
from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family and other
cytokine receptor families. It is also important for transducing a signal by type I and type II
interferons, and members of the IL-10 family via type II cytokine receptors. JAK2 has been
implicated in signaling by the GM-CSF receptor family and controls various functions relating to
hematopoiesis. JAK3 is involved in signal transduction by receptors that employ the common
gamma chain of the type I cytokine receptor family (e.g., IL-2R, IL-4R, IL-7R, IL-9R, IL-15R,
and IL-21R) (Villarino 2017). Finally, Tyk2 is important for Th1 and Th17 responses,
transducing signals by interferons, IL-12, IL-23, IL-22, and IL-6 (O’Shea 2019).
The first demonstration of the clinical efficacy of JAK inhibitors in eczema utilized a topical
formulation of the pan-JAK inhibitor, tofacitinib, which has been approved orally for the
treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis (Bissonnette 2016a).
Subsequently, several topical JAK inhibitors (delgocitinib, ruxolitinib) (Kim 2019;
Nakagawa 2018, Worm 2019) and oral JAK inhibitors (upadacitinib, PF-04965842, baricitinib)
(Guttman-Yassky 2019a; Gooderham 2019; Guttman-Yassky 2019b) have been reported to have
efficacy in the treatment of eczema. Oral JAK inhibitors can be accompanied by safety issues
including the development of opportunistic infections, lymphoma and other malignancies, and
hematologic and lipid abnormalities. We are pursuing development of ARQ-252 cream, a topical
form of the JAK1 selective inhibitor SHR0302, as a potential treatment for particular forms of
eczema aiming to maintain the efficacy of this class of agents in these diseases while minimizing
systemic exposure and undesirable side effects.
SHR0302 is in Phase 2 development as an oral therapy for rheumatoid arthritis (RA), Crohn’s
disease, ulcerative colitis, and atopic dermatitis by development partners Jiangsu Hengrui
Medicine Company (Hengrui) and Reistone Biopharma. Clinical safety data from these ongoing
programs, as well as extensive nonclinical studies, provide support for Arcutis’ dermal
(ARQ‑252) development program.


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Nonclinical Safety Summary
In vitro pharmacology data supports that SHR0302 is a strong JAK inhibitor, with
JAK1>JAK2>JAK3> Tyk2 inhibitory activity. Additionally, SHR0302 has demonstrated
activity comparable to tofacitinib in various in vivo models of inflammatory conditions,
including the imiquimod-induced murine model of psoriasis, the oxazolone-induced murine
model of atopic dermatitis, the rat and murine models of collagen-induced arthritis, the
adjuvant-induced arthritis rat model, and the murine dextran sulfate sodium-induced colitis
model.
The nonclinical safety profile of orally administered SHR0302 has been well characterized
through the conduct of safety pharmacology, acute and repeat dose toxicity in rats and monkeys,
genetic toxicology (bacterial reverse mutation, in vitro micronucleus, in vivo micronucleus in
rats), and reproductive/developmental toxicology (fertility, embryofetal development) studies.
In safety pharmacology studies, SHR0302 did not cause significant changes in cardiovascular,
CNS or respiratory functions. After oral administration, SHR0302 was well absorbed and
distributed into many tissues.
During the oral dosing program of SHR0302 with dose levels up to 150 mg/kg/day in rats and
15 mg/kg/day in monkeys, the major target organs identified following repeated dosing were
immune system (lymph nodes, spleen, and thymus), bone marrow, reproductive organs and
digestive tract. As SHR0302 is a potent inhibitor of Janus kinases which are known to affect
cytokine-mediated signaling, the immunomodulatory effects observed (mainly in the rat) in the
toxicity studies are consistent with the pharmacological mechanism of action of SHR0302.
The genotoxicity studies on SHR0302 indicate a lack of potential to induce point mutations,
chromosomal aberrations, or to interact with or damage DNA. Therefore, it is unlikely that
SHR0302 poses a genotoxic risk to humans.
Results of a rat fertility study with SHR0302 showed no effects on male fertility and disrupted
early embryonic development in female rats at 10 and 50 mg/kg. The no observed adverse effect
level (NOAEL) was 50 mg/kg for male fertility and 1 mg/kg for female fertility and early
embryonic development. Embryofetal development studies in rats demonstrated maternal and
fetal toxicity and fetal teratogenicity following oral dosing of SHR0302. The NOAEL for rat
dams was 10 mg/kg and 1 mg/kg for embryofetal effects. In the rabbit embryofetal study, no
maternal toxicity was noted at the high dose of 25 mg/kg/day (NOAEL). Rabbit embryo-fetal
developmental toxicity was noted with effects on fetal viability and development, including fetal
visceral and/or skeletal malformations and resulting in a NOAEL of 1 mg/kg/day.
The nonclinical safety profile of SHR0302 was also evaluated topically in mice and minipigs in
support of once-daily topical administration. Dermal toxicology studies conducted to date
include 13-week mouse, 7-day tolerability in minipigs, 4-week and 16-week toxicity in minipigs,
and local tolerance (ocular irritation, skin sensitization, in vitro phototoxicity). Planned studies
include 39-week toxicity in minipigs and a 104-week carcinogenicity study in mice.


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The dermal toxicity of ARQ-252 (SHR0302 cream) has been evaluated and no new risks have
been identified and no target organs were identified. In the 13-week dermal toxicity study in
mice and the 7-day and 16-week dermal toxicity studies in minipigs, no evidence of systemic
toxicity was observed, and no dermal findings were noted. The NOAELs in each of these repeat
dose dermal toxicity studies were the highest doses administered.
Local tolerance studies demonstrated ARQ-252 is not a skin sensitizer or eye irritant, and it does
not have phototoxic potential.
Overall, the results suggest that topical ARQ-252 cream is safe and well tolerated in both mice
an minipigs. Taken together, the results of the nonclinical toxicology studies demonstrated an
acceptable topical safety profile and support the progression of ARQ-252 cream into clinical
studies in patients with hand eczema.
Clinical Studies
This will be the first study of topical ARQ-252 cream in the human population.
Oral administration of SHR0302 has been studied in three Phase 1 pharmacokinetic studies,
including two conducted in healthy volunteers and one conducted in subjects with rheumatoid
arthritis. Oral administration of SHR0302 has also been studied in a 24-week, Phase 2 study in
subjects with rheumatoid arthritis.
Oral Administration: Phase 1
In three Phase 1 pharmacokinetic studies, a total of 94 subjects were exposed to SHR0302 at
various dosages and duration. The single maximum dose of exposure in humans was 100 mg,
and the longest duration of exposure was 7 days of 10 mg SHR0302 in rheumatoid arthritis
patients.
A study on human safety, pharmacokinetics, and pharmacodynamics was conducted on
SHR0302 following single dose oral administration in healthy subjects (SHR0302-101).
This was a randomized, double blind and placebo-controlled study with six dosage groups of
1, 5, 10, 25, 50 and 100 mg. AEs were reported mainly from the high-dose groups (50 mg and
100 mg) in this single ascending dose study. The most common AEs involved the hematologic
system (neutropenia and high lymphocyte count). Adverse reactions included neutropenia in
7 subjects (10.9%), elevated lymphocytes in 6 subjects (9.4%), and leukopenia in 1 subject
(1.6%). At the 25 mg dose and below, there was no obvious difference between the active and
placebo arms. There were no serious adverse events.
Following single oral dose administration, SHR0302 was rapidly absorbed with median Tmax
values of 1.0 hour across all dose groups. Geometric mean Cmax values increased 105-fold over
the 100-fold increase in dose (1 to 100 mg), demonstrating dose proportional kinetics. Similarly,
the geometric mean AUC0-24 values increased 107-fold over the same 100-fold increase in dose.


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A multiple ascending dose (MAD) study of human safety, pharmacokinetics, and
pharmacodynamics was conducted on orally administered SHR0302 in subjects with rheumatoid
arthritis (SHR0302-102). This was a randomized, double-blind, and placebo-controlled study
with four planned dosage groups of 2, 5, 10 and 25 mg. Each dosage group had 12 subjects,
10 receiving active and 2 receiving placebo. Subjects were dosed for 7 days. The 2, 5, and 10 mg
dose groups were completed, for a total of 36 subjects, 30 receiving active drug. No subjects in
the 25 mg dose group were enrolled.
Twenty out of 36 subjects experienced AEs during the study period, with 16 subjects
experiencing AEs reported as causally related to drug. AEs reported in subjects exposed to
SHR0302 included seven cases of elevated TSH, five cases of elevated alanine aminotransferase,
four cases of elevated aspartate aminotransferase, three cases of anemia, three cases of urinary
tract infection, two cases of lowered free thyroxine, and one case each of ear pain, conjunctivitis,
hypoesthesia, constipation and hematuria. Elevated TSH in blood (five cases), urinary tract
infection (three cases) and lowered free thyroxine (two cases) were concentrated in the 10 mg
SHR0302 group. All AEs were Grade 1 or Grade 2, and most reversed within two weeks of drug
discontinuation. No SAEs were reported. Study drug dose was not decreased or suspended in
any subject due to an AE, and no subject withdrew from the trial due to an AE.
Following multiple oral dose administrations of SHR0302, the median Tmax value was 1.0 hour
across the dose groups. Geometric mean Cmax values increased 3.5-fold over the 5-fold increase
in dose (2 to 10 mg), demonstrating less than dose proportional kinetics. Similarly, the geometric
mean AUC0-24 values increased 4.1-fold over the same 5-fold increase in dose from
1130 hr*ng/mL for the 2 mg dose to 4620 hr*ng/mL for the 10 mg dose.
A food effect study of high-fat intake on the pharmacokinetics of SHR0302 has also been
conducted (SHR0302-103). In this study, SHR0302 (10 mg tablet) was safe and well tolerated in
healthy subjects, and administration of SHR0302 after a high-fat meal did not significantly
impact systemic exposure. Except for one AE (soft tissue contusion) unrelated to drug which
was moderate, the other AEs were mild and recovered without treatment. No SAEs were
reported, and no subject withdrew from the trial due to an AE.
Overall, SHR0302 was well-tolerated with no SAEs reported.
Oral Administration: Phase 2
Preliminary results are available from SHR0302-201, a Phase 2, double-blind, randomized study
evaluating 0.5 mg, 1 mg, 2 mg, 4 mg, and 8 mg of SHR0302 as once-daily oral monotherapy for
adults with active rheumatoid arthritis who were naïve to any disease modifying anti-rheumatic
drug (DMARDs) or have had an inadequate response or intolerance to conventional synthetic
DMARDs. The study was placebo-controlled for 12 weeks, followed by a 12-week, open label
maintenance phase. The Primary Endpoint was the response rate of American College of
Rheumatology 20 (ACR20) at Week 12, which is a composite measure defined as 20%
improvement in the number of tender and swollen joints, and 20% improvement in 3 of 5 criteria
including patient global assessment, physician global assessment, functional ability measure,


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visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein. A total of
194 subjects were randomized. 174 subjects completed the placebo-controlled period.
Preliminary efficacy results include:
•
SHR0302 monotherapy was demonstrated to be effective for treatment of active
rheumatoid arthritis, with improvements in clinical signs and symptoms, as well as
physical function versus placebo.
•
A dose response relationship was observed, with the SHR0302 8 mg group having more
responders than the other groups.
•
The Primary Endpoint was met in the 2 mg, 4 mg, and 8 mg groups (refer to Table 1).
Table 1.
Proportion of Patients Reaching ACR20/50/70 and Statistical Check
(CMH-FAS-NRI) after 12-week Administration in a Multicenter,
Randomized, Double-blind, Placebo-controlled Phase II Study Evaluating
the Efficacy and Safety of SHR0302 Tables in Patients with Moderate to
Severe Active Rheumatoid Arthritis
Indicator
Group
Placebo
0.5 mg
1 mg
2 mg
4 mg
8 mg
(N=37)
(N=25)
(N=24)
(N=23)
(N=40)
(N=45)
ACR20
Percentage
(%)
27.0
44.0
41.7
56.5
67.5
77.8
(95% CI)
(13.8, 44.1)
(24.4, 65.1)
(22.1, 63.4)
(34.5, 76.8)
(50.9, 81.4)
(62.9, 88.8)
% difference
from placebo
-
17.0
14.6
29.5
40.5
50.8
(95% CI)
(-6.6, 39.2)
(-8.8, 37.3)
(4.1, 50.8)
(18.2, 57.5)
(29.5, 65.9)
P value
-
0.1871
0.2884
0.0223
0.0004
<0.0001
ACR50
Percentage
(%)
2.7
12.0
20.8
30.4
27.5
37.8
(95% CI)
(0.1, 14.2)
(2.5, 31.2)
(7.1, 42.2)
(13.2, 52.9)
(14.6, 43.9)
(23.8, 53.5)
% difference
from placebo
-
9.3
18.1
27.7
24.8
35.1
(95% CI)
(-4.3, 27.4)
(2.1, 37.9)
(9.2, 48.3)
(8.9, 40.3)
(18.2, 49.8)
P value
-
0.1661
0.0247
0.0022
0.0031
0.0002
ACR70
Percentage
(%)
0.0
4.0
4.2
13.0
12.5
26.7
(95% CI)
(0.0, 9.5)
(0.1, 20.4)
(0.1, 21.1)
(2.8, 33.6)
(4.2, 26.8)
(14.6, 41.9)
% difference
from placebo
-
4.0
4.2
13.0
12.5
26.7
(95% CI)
(-6.0, 19.5)
(-5.8, 20.2)
(0.4, 32.1)
(0.8, 26.1)
(12.4, 41.0)
P value
-
0.2440
0.1797
0.0267
0.0284
0.0007
Investigator’s Brochure, Edition 1.0, Feb 2020.


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Preliminary safety results include:
•
SHR0302 was generally safe and well tolerated. A higher frequency of infections was
observed in SHR0302-treated subjects, particularly in the 8mg group. The most common
infections included upper respiratory tract infections and urinary tract infections.
•
Mean WBC, neutrophils, lymphocyte, HGB, platelet count, serum lipid level, liver
function, kidney function, and thyroid function parameters remained in the normal range
in all SHR0302 treatment groups.
•
Mean platelet count did not increase during the study.
•
Increases in LDL, HDL, total cholesterol and triglycerides were observed. However,
LDL-to-HDL remained stable.
•
Increase in mean serum creatine kinase (CK) was observed in patients treated with
SHR0302 versus placebo but was within normal range. CK-MB remained stable.
•
Most of the reported abnormal laboratory results were classified as CTCAE grade 1 or 2.
CTCAE grade 3 events included: 1 case of increased alanine aminotransferase (4 mg),
1 case of decreased neutrophils (8 mg), 1 case of decreased lymphocytes (4 mg) and
1 case of anemia (8 mg).
•
From Baseline through Week 12, the most common AEs (≥5% across pooled SHR0302
groups) included upper respiratory infection, hyperlipidemia, swollen joint, urinary tract
infection, hypercholesterolemia, joint pain, and cough. From Baseline to Week 12, other
TEAEs occurring at rates ≥5% in individual SHR0302 groups (although <5% across
pooled SHR0302 groups) included hypothyroidism, anemia, liver dysfunction (although
placebo group had highest rate), elevated serum creatine phosphokinase, diarrhea,
headache, hematuria, abdominal discomfort, urine protein detection, blood in urine,
elevated blood lactic dehydrogenase, and upper abdominal pain. Additional common
AEs (≥5% across pooled SHR0302) seen from Baseline through Week 24 included
elevated serum creatine phosphokinase, anemia, and hypothyroidism.
•
Overall, there were 6 severe AEs in 3 subjects including 4 severe SAEs in a subject in the
0.5 mg group during the placebo-controlled period (Craniocerebral injury, Ventricular
hemorrhage, Occipital fracture and Subarachnoid hemorrhage), appendicitis in a subject
in the 4 mg group during the placebo-controlled period, and elevated liver enzymes in a
subject in the 4 mg group during the extension period.
•
AEs leading to discontinuation were generally uncommon from Baseline through
Week 12 (1 or fewer subjects per group). From Baseline through Week 24, AEs leading
to discontinuation remained generally uncommon (1 or fewer subjects per group, except
for 3 subjects in the 4 mg group, and 3 subjects in 8 mg group including 1 subject in
placebo group then received 8 mg after Week 12).
•
A total of 4 cases of herpes zoster (all in 8 mg group) and 1 case of opportunistic
infection (8 mg group, cryptococcal pneumonia) were reported.
•
No tuberculosis, malignancy, important cardiac events or death were reported.
•
One thrombotic event was reported, a SAE of multiple lacunar infarcts in a 64 year-old
woman in the 0.5mg SHR0302 group, requiring hospitalization, deemed unrelated, with
dose not changed.


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•
From Baseline through Week 12, there were 13 SAEs in 9 subjects overall, including
3 SAEs in 2 subjects in the placebo group, 5 SAEs (Craniocerebral injury, Ventricular
hemorrhage, Occipital fracture and Subarachnoid hemorrhage; Lacunar infarction) in
2 subjects in the 0.5 mg group, 3 SAEs (Hemorrhoids; Pulmonary infection;
Appendicitis) in 3 subjects in the 4 mg group, and 2 SAEs (Epiglottic cyst; Tympanitis)
in 2 subjects in the 8 mg group. From Week 12 through Week 24, there were 4 SAEs in
3 subjects, including Liver dysfunction in a subject in the 4 mg group, Viral
gastroenteritis in a placebo-8 mg subject, and Cryptococcal pneumonia and Ureterolith in
a subject in the 8 mg group.
Additional Studies
An open label, self-controlled study (SHR0302-105) evaluating drug interaction potential
between SHR0302 and methotrexate (MTX) in subjects with rheumatoid arthritis was recently
completed. Subjects were to take MTX 10 mg once daily on Day 1 and Day 8, and SHR0302
10 mg once daily on Days 3 to Day 8. Overall, 15 subjects were enrolled. A total of 18 adverse
events were reported in 8 of 15 subjects (53.3%). Of the 18 adverse events, 3 subjects (20.0%)
reported 5 adverse events after SHR0302 alone, 4 subjects (26.7%) reported 5 adverse events
after MTX alone, and 3 subjects (20.0%) reported 8 adverse events after MTX and SHR0302 in
combination. The adverse events reported in subjects given SHR0302 alone included headache,
back pain, fever, constipation and tachycardia each in 1 subject (6.7%). The adverse events
reported by the subjects after MTX and SHR0302 in combination included anemia, upper
respiratory tract infection, urinary tract infection, elevated blood triglycerides, elevated aspartate
aminotransferase, positive urine leukocytes and tachycardia each in 1 subject (6.7%). No serious
adverse events were reported, and no subjects withdrew prematurely due to adverse event.
Ongoing Studies
Two studies of SHR0302 as an oral treatment of inflammatory bowel disease are ongoing.
RSJ10101 is a phase 2, randomized, placebo-controlled, double-blind, 4 arm, dose-ranging
study to evaluate the efficacy and safety of SHR0302 compared to placebo in adults with
moderate to severe, active ulcerative colitis. Treatment groups include 3 different doses of
SHR0302 (4mg QD, 8mg QD, 4mg BID) or placebo, with 1:1:1:1 randomization. The study
consists of an 8-week blinded treatment phase, followed by an 8-week of blinded, active
extension phase. Planned enrollment is 152 across China, Ukraine, United States, and Poland.
RSJ10201 is a phase 2, randomized, placebo-controlled, double-blind, four arms dose-ranging
study to evaluate the efficacy and safety of SHR0302 compared to placebo in adults with
moderate to severe, active Crohn’s disease. Treatment groups include 3 different doses of
SHR0302 (4mg QD, 8mg QD, 4mg BID) or placebo, with 1:1:1:1 randomization. The study
consists of a 12-week blinded treatment phase, followed by a 12-week of blinded, active
extension phase. Planned enrollment is 144 across China, Ukraine, United States, and Poland.
Analysis of blinded data from these two ongoing studies in IBD (RSJ10101 and RSJ10201) as of
October 19, 2019 has been performed. Based on this analysis, 39 subjects were estimated to be
exposed to SHR0302 in these two clinical trials. One SAE was reported as colitis ulcerative and
the other one was synovitis. The latter SAE was unblinded and confirmed to be on SHR0302.


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Overall, the reported safety data were in line with the known and expected safety profile of
SHR0302.
Finally, two additional studies of SHR0302 recently started, for which no data is currently
available. RSJ10303 is a phase 2 study in China of SHR0302 in atopic dermatitis. The study is
a randomized, double-blind, and placebo-controlled, evaluating the efficacy and safety of
SHR0302 4mg QD, SHR0302 8mg QD, or placebo in adult patients with moderate to severe
atopic dermatitis. RSJ10411 is a phase 1, vehicle-controlled study in Australia and China to
evaluate the safety and pharmacokinetics of SHR0302 base ointment at single dose and multiple
dose in healthy adult subjects.
Rationale for Development
Since the first demonstration of the clinical efficacy of JAK inhibitors for the treatment of
eczema, which utilized a topical formulation of tofacitinib for the treatment of atopic dermatitis,
numerous oral JAK inhibitors and several other topical JAK inhibitors have also demonstrated
efficacy in eczema. We are pursuing the development of ARQ-252 cream as a topical
JAK1-selective inhibitor for the treatment of hand eczema, planning to take advantage of the
efficacy of this class of agents in this disease, while minimizing systemic exposure and
undesirable side effects. Nonclinical and systemic clinical data with SHR0302 to date are
supportive of this plan.
The above data indicate that topical ARQ-252 could provide an important addition to the
dermatologist’s approach for treating hand eczema.
Dose Selection
ARQ-252 cream 0.3% was selected as the high clinical dose because this dose remains in
solution when stored at controlled room temperature.
In Cohort 1 of this study, ARQ-252 cream 0.3% will be applied QD to approximately 4% BSA
in subjects with hand eczema. It is well known that cutaneous disease states can alter drug
permeability as compared to normal human skin. Since eczematous skin may have different drug
permeability characteristics than normal skin (Ortiz 2009; Halling-Overgaard 2017), this study is
planned in patients with hand eczema rather than healthy volunteers. Administration of
ARQ‑252 cream 0.3% once-daily to approximately 4% of BSA at an application rate of
approximately 0.75 mg/cm2 would result in 1.5 mg of total SHR0302 being absorbed per day,
assuming 100% absorption of applied drug, an amount well covered by the oral MAD study
discussed previously (Section 2.3.1). In the oral MAD, daily doses of 2 to 10 mg resulted in
signals for thyroid effects (elevated TSH, decreased free T4), mild LFT abnormalities, and a few
urinary tract infections. These are all easily monitored, and skin absorption is very likely to be
only a small fraction of 100%. Moreover, in the Phase 2 RA study, mean WBC, neutrophils,
lymphocyte, HGB, platelet count, liver function and kidney function remained in the normal
range in all SHR0302 treatment groups.


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Following a review of safety and PK data from Phase 1 (Cohort 1) of this study, Phase 2b
(Cohort 2) can commence. Phase 2b (Cohort 2) is a parallel group, double blind,
vehicle-controlled cohort in which subjects with chronic hand eczema will be randomized to
ARQ-252 cream 0.3% QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1% QD, vehicle
cream BID or vehicle cream QD.
Risks and/or Benefits to Subjects
The potential risks of ARQ-252 cream stem from what is known about the safety of the oral form
of this drug, and risks associated with the JAK inhibitor mechanism. These risks include serious
infections, other infections (e.g., upper respiratory tract infections, opportunistic infections,
herpes), anemia, lymphopenia, natural killer (NK) cell reduction, neutropenia, platelet elevations
or reductions, malignancy and lymphoproliferative disorders, gastrointestinal perforations, liver
function abnormalities, thyroid function abnormalities, lipid elevation, serum creatinine
elevations, creatine phosphokinase elevations, thrombosis, nausea, diarrhea, headache, and
hypertension. In general, topical delivery is expected to carry lower risk than oral administration
at therapeutic doses to the degree that systemic exposure is reduced. Previous nonclinical
research showed that the active ingredient in ARQ-252 can harm fetal development. Please refer
to the Investigator’s Brochure for detailed information.
Phase 1 (Cohort 1)
Subjects in Cohort 1 subjects may see an improvement in their hand eczema, although the study
duration of 2 weeks may limit this possibility.
Phase 2b (Cohort 2)
Subjects randomized to active treatment in Cohort 2 may see an improvement in their hand
eczema with the use of ARQ-252 cream. Those receiving vehicle cream may also see
improvement related to the moisturizing properties of the vehicle
The safety monitoring practices employed in this protocol (i.e., physical examinations,
application site reaction assessments, hematology, serum chemistry, TSH, T4, urinalysis, ECG,
and AE questioning) are adequate to protect the subjects’ safety and should detect expected AEs.
3.
STUDY ENDPOINTS AND OBJECTIVES
Study Objectives
Primary Objectives
The objectives of this study are as follows:
Phase 1 (Cohort 1):
•
To assess the safety, tolerability and PK of QD application of ARQ-252 0.3% to both
hands for 2 weeks in 6 subjects with chronic hand eczema


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Phase 2b (Cohort 2):
•
To assess the safety and efficacy of ARQ-252 cream 0.1% QD and ARQ-252 cream
0.3% QD and BID, vs vehicle applied QD and BID for 12 weeks to subjects with chronic
hand eczema
Study Endpoints
Primary Endpoints
Phase 1 (Cohort 1):
The primary endpoint of Cohort 1 is safety, as measured by the incidence and severity of adverse
events, changes in laboratory parameters, tolerability, and pharmacokinetics.
Phase 2b (Cohort 2):
The primary endpoint of Cohort 2 is:
•
The rate of an IGA score of ‘clear’ or ‘almost clear’ at Week 12
Secondary Endpoints
Phase 2b (Cohort 2):
The secondary endpoints of Cohort 2 are:
•
The rate of achievement of IGA of ‘clear’ or ‘almost clear’ PLUS at least a 2-point
improvement from Baseline at Weeks 2, 4, 8 and 12
•
The rate of achievement of at least a 2-point improvement from Baseline at Weeks 2, 4, 8
and 12
•
Achievement of IGA of ‘clear’ or ‘almost clear’ at Weeks 2, 4, and 8
•
Time to IGA of ‘clear’ or ‘almost clear’
•
Change in IGA score at Weeks 2, 4, 8, and 12 as compared to Baseline
•
Change in WI-NRS pruritus score at 2 weeks, 4 weeks, 8 weeks, and 12 weeks compared
to Baseline
•
The rate of achievement of ≥4-point reduction from Baseline in WI-NRS pruritus score at
2 weeks, 4 weeks, 8 weeks, and 12 weeks in subjects with Baseline WI-NRS pruritus
score of at least 4
•
Time to the first achievement of ≥4-point reduction from Baseline in WI-NRS pruritus
score in subjects with Baseline WI-NRS pruritus score of at least 4
•
Percent change in HECSI (Hand Eczema Severity Index) score at Weeks 2, 4, 8, and 12
compared to Baseline
•
Change in Pain NRS score at 2 weeks, 4 weeks, 8 weeks, and 12 weeks compared to
Baseline


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•
The rate of achievement of ≥4-point reduction from Baseline in Pain NRS score at
2 weeks, 4 weeks, 8 weeks, and 12 weeks in subjects with Baseline Pain NRS score of at
least 4
•
Time to the first achievement of ≥4-point reduction from Baseline in Pain NRS score in
subjects with Baseline Pain NRS score of at least 4
•
Change from baseline in overall Quality of Life in Hand Eczema Questionnaire
(QOLHEQ) score at each visit
•
Percent BSA affected by disease and % change from baseline in BSA affected by disease
at baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Exploratory Endpoints
Phase 2b (Cohort 2):
The exploratory endpoint of Cohort 2 is:
•
Change from Baseline in Nail Dystrophy at each visit.
4.
INVESTIGATIONAL PLAN
Overall Study Design and Plan
This is a phase 1/2b, multiple dose and 12-week, parallel group, double blind, dose ranging,
vehicle-controlled study of the safety and efficacy of ARQ-252 cream 0.1% and ARQ-252 cream
0.3% in subjects with chronic hand eczema.
There are 2 cohorts of subjects:
•
Cohort 1 is a multiple dose cohort in which subjects with chronic hand eczema will be
assigned to ARQ-252 cream 0.3% QD x 2 weeks to be applied to both hands. PK and
tolerability will be evaluated.
•
Cohort 2 is a parallel group, double blind, vehicle-controlled cohort in which subjects with
chronic hand eczema will be randomized to ARQ-252 cream 0.3% QD, ARQ-252 cream
0.3% BID, ARQ-252 cream 0.1% QD, vehicle cream BID or vehicle cream QD x 12 weeks
to be applied to both hands. Safety and efficacy will be evaluated.
Number of Sites and Subjects
A total of approximately 6 evaluable subjects will be enrolled in Cohort 1 and a total of
approximately 215 subjects will be enrolled in Cohort 2. Approximately 45 study sites are
planned in the US, Canada and Australia. During the conduct of the study, additional countries
and/or sites may be added if necessary. Subjects will be adults (≥18 years of age) males or
females with chronic hand eczema.
For Cohort 1, evaluable subjects are defined as those that:
•
Complete 2 weeks of treatment


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•
Have PK results for all timepoints required at D1, D2, D15 and D16.
Unevaluable subjects in Cohort 1 may be replaced. Subjects in Cohort 2 will not be replaced.
Subject Participation
Phase 1 (Cohort 1)
Subject participation involves a minimum of 7 clinic visits including Screening, Baseline/Day 1,
Day 2, Day 8, Day 15, Day 16 and Day 22. Subjects will be treated with investigational product
(ARQ-252 cream 0.3% QD) for 2 weeks. The interval between the Screening and Baseline visits
could be up to 4 weeks, therefore the anticipated maximum duration of subject participation is
7 weeks.
Phase 2b (Cohort 2)
Subject participation involves a minimum of 7 clinic visits including Screening, Baseline/Day 1,
Week 2, Week 4, Week 8, Week 12 and Week 13. Subjects will be randomized to a treatment
group and will be treated with investigational product for 12 weeks. The interval between the
Screening and Baseline visits could be up to 4 weeks, therefore the anticipated maximum
duration of subject participation is 17 weeks.
Randomization
Phase 1 (Cohort 1)
Phase 1 (Cohort 1) is open label and all enrolled subjects will be assigned treatment with
ARQ‑252 cream 0.3% QD at the Baseline visit. Subjects will be enrolled at the Baseline visit
after the Investigator confirms that the subject meets all eligibility criteria listed in Section 4.7.
Enrollment will be documented by the completion of the Enrollment Notification Form.
Phase 2b (Cohort 2)
Phase 2b (Cohort 2) is randomized. Randomization will take place at the Baseline visit after the
Investigator confirms that the subject meets all eligibility criteria listed in Section 4.7. Subjects
will be randomly assigned to apply ARQ-252 0.3% QD, ARQ-252 0.3% BID, ARQ-252 0.1%
QD, vehicle cream QD or vehicle cream BID by an interactive response technology system
(IRT).
Assignment of treatment arm will be made at a 2:2:1:1:1 ratio and stratified by study site and
IGA at baseline according to a computer-generated randomization list. Kits containing tubes of
investigational product will be assigned to each subject by the IRT system. A subject may
receive more than one kit for the treatment period. The kits and tubes will be labeled with a
unique number, in a blinded manner.


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Numbering of Subjects
Phase 1 (Cohort 1)
All subjects who sign informed consent will be assigned a unique six-digit subject ID number by
the site. The first three digits will correspond to the site number (assigned by the Sponsor) and
the next three digits correspond to the sequential order in which the subject is screened for the
study.
Phase 2b (Cohort 2)
All subjects who sign informed consent will be assigned a unique six-digit subject ID number by
the IRT system. The first three digits correspond to the site number (assigned by the Sponsor),
the next three digits correspond to the sequential order in which the subject is screened for the
study.
The clinical site is responsible for maintaining a current log of subject ID number assignments
and the kit number assigned to that subject. The subject ID number is required to be entered on
all clinical study documentation (e.g., case report forms, labeling of clinical materials and sample
containers, investigational product accountability logs, etc.).
Blinding
Phase 1 (Cohort 1) is not blinded.
Phase 2b (Cohort 2) is double-blinded, therefore neither the subjects nor the Investigator and
clinical personnel will be aware of which investigational product (ARQ-252 0.1% cream,
ARQ‑252 0.3% cream or vehicle cream) an individual subject receives. The subjects,
Investigator and clinical personnel will be aware of whether IP is to be applied QD (once daily)
or BID (twice daily).
Breaking Treatment Codes
Phase 2b (Cohort 2)
In the event of a medical emergency where breaking the blind is required to provide medical care
to the subject, the Investigator may obtain treatment assignment directly from the IRT system for
that subject. Refer to the current version of the IRT plan for details on unblinding. Treatment
assignment should, however, remain blinded unless the assignment knowledge is necessary to
determine subject emergency medical care. The rationale for unblinding must be clearly
explained in source documentation and on the CRF, along with the date on which the treatment
assignment was obtained. The Investigator is requested to contact the Sponsor promptly in the
event of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a
subject’s treatment assignment is disclosed to the Investigator, the subject will have the study
treatment discontinued. All subjects will be followed until study completion unless consent to do
so is specifically withdrawn by the subject.


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Selection of Study Population
Inclusion Criteria
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the
study:
1. Participants legally competent to sign and give informed consent.
2. Males and females 18 years of age and older (inclusive) at the time of consent.
3. Clinical diagnosis of chronic hand eczema, defined as hand eczema persistent for more than
3 months, or returned twice or more within the last 12 months (Diepgen 2009). Generally
stable disease for 6 weeks. Both irritant and non-irritant etiologic forms are allowed.
All morphologic types are allowed, e.g., vesicular/dyshidrotic, hyperkeratotic, nummular,
and other types.
4. An Investigator’s Global Assessment of disease severity (IGA) of at least Mild (‘2’) at
Baseline (Visit 2). (In Cohort 2, subjects with IGA of ‘Mild’ will be limited to 20% of total
enrollment, and subjects with IGA of ‘Severe’ subjects will also be limited to 20% of total
enrollment).
5. Chronic hand eczema involving at least 0.3% body surface area total (i.e., approximately a
third of one handprint) lesions on both hands added together at Baseline (Visit 2).
6. Female subjects of childbearing potential (FOCBP) must have a negative serum pregnancy
test at Screening and negative urine pregnancy test at Baseline (Visit 2). For FOCBP
involved in any sexual intercourse that could lead to pregnancy: the subject must agree to use
a highly effective contraceptive method for at least 4 weeks prior to Day 1. Additionally,
from Day 1 until at least 4 weeks after the last investigational product administration, these
subjects must agree to use at least 1 highly effective contraceptive method in addition to
1 barrier method according to Contraception Requirements (Figure 1).
7. Females of non-childbearing potential must either be post-menopausal with spontaneous
amenorrhea for at least 12 months (post-menopausal status will be confirmed with FSH
testing) or have undergone surgical sterilization (permanent sterilization methods include
hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, or bilateral salpingectomy)
according to Contraception Requirements (Figure 1).
8. Males, if engaging in sexual intercourse with a female who is pregnant or a female of
childbearing potential, must agree to use a condom every time during the study and every
time subsequently until 4 weeks after the last investigational product administration.
9. Males must agree not to donate sperm from the first dose of investigational product until
4 weeks after the last investigational product administration.
10. Subjects in good health as judged by the Investigator, based on medical history, physical
examination, 12-lead electrocardiogram (ECG), serum chemistry labs, hematology values,
and urinalysis.
11. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule,
according to the judgment of the Investigator.


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Exclusion Criteria
Subjects who meet any of the following exclusion criteria will be excluded from participation in
this study:
1. Concurrent skin diseases on the hands which, in the opinion of the Investigator, could
confound the study (e.g., tinnea manuum).
2. Active skin diseases not on the hands such as atopic dermatitis or psoriasis requiring medical
treatment that could significantly affect hand eczema, in the Investigator’s opinion.
3. Subjects with any presence or history of psoriasis.
4. History of a positive patch test with continued exposure to allergen. If, in the opinion of the
Investigator, there is any suspected allergic hand eczema with continued exposure to
allergen, subject must undergo diagnostic patch testing to determine if they meet entry
criteria prior to Baseline (Visit 2).
5. Subjects who cannot discontinue systemic and/or topical therapies for the treatment of
chronic hand eczema prior to Baseline (Visit 2) and during the study according to Excluded
Medications and Treatments (Table 2), (i.e., immunosuppressive drugs, immunomodulating
drugs, retinoids, or corticosteroids).
6. Psoralen ultraviolet A (PUVA) or ultraviolet B (UVB) therapy on the hands within 4 weeks
prior to Baseline (Visit 2).
7. Cutaneously applied treatment with immunomodulators (e.g., phosphodiesterase-4 (PDE-4)
inhibitors, pimecrolimus, tacrolimus), topical urea moisturizers, topical antibiotics, or low or
mid potency topical corticosteroids on the hands or elsewhere within 1 week prior to
Baseline (Visit 2). Cutaneously applied treatment with high potency topical corticosteroids
on the hands or elsewhere within 2 weeks prior to Baseline (Visit 2).
8. Subjects that have significant active systemic or localized infection, including known
actively infected eczema or have had any infection that required oral or intravenous
administration of antibiotics, antifungal or antiviral agents within 2 weeks prior to Baseline
(Visit 2).
9. Other cutaneously applied therapy on the hands (except for the use of subject's own non-urea
and non-salicylic acid emollients) within 1 week prior to Baseline (Visit 2).
10. Subjects who are unwilling to refrain from using a tanning bed or other LEDs as well as
outdoor tanning or excessive sun exposure for 4 weeks prior to Baseline (Visit 2) and during
the study.
11. Subjects with a history of chronic alcohol or drug abuse within 6 months prior to Baseline
(Visit 2).
12. Current or a history of cancer within 5 years with the exception of fully treated skin basal cell
carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix.
13. Subjects that have received live vaccine therapy less than 4 weeks prior to Baseline (Visit 2),
immunosuppressive drugs less than 4 weeks prior to Baseline (Visit 2), or have known
infection with mycobacterium tuberculosis, hepatitis B or C, or HIV, or have a diagnosis of
an immunodeficiency disorder.


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14. Subject had a major surgery within 4 weeks prior to Baseline (Visit 2) or has a major surgery
planned during the study.
15. Known or suspected:
•
severe renal insufficiency or severe hepatic disorders
•
hypersensitivity to component(s) of the investigational product which include SHR0302,
butylated hydroxytoluene (BHT), benzyl alcohol, dimethyl sulfoxide, cyclomethicone,
dimethicone (350 cst), ST-Elastomer 10, water, propylene glycol, polyethylene glycol
200, Pemulen TR1, Carbopol 974P, ethylenediaminetetraacetic acid, trolamine and
D-limonene.
16. Pregnant or lactating women or women planning to become pregnant during the study and /
or within 28 days following the last dose of investigational product.
17. Subjects who cannot discontinue the use of strong systemic Cytochome P-450 3A4 inducers
e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin,
rifampin and carbamazepine for 2 weeks prior to Baseline (Visit 2) and during the study
period.
18. Subjects who cannot discontinue the use of strong systemic Cytochome P-450 3A4 inhibitors
e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, fluconazole,
nefazodone, saquinavir, suboxone and telithromycin for 2 weeks prior to Baseline (Visit 2)
and during the study period.
19. Subjects with any serious medical condition or clinically significant laboratory, ECG, vital
signs or physical examination abnormality that would prevent study participation or place
the subject at significant risk, as judged by the Investigator.
Removal of Subjects from Investigational Product
A subject may discontinue investigational product for any of the following reasons:
•
Occurrence of any medical condition or circumstance that, in the opinion of the
Investigator, does not allow the subject to adhere to the requirements for investigational
product as per the protocol.
•
Adverse Events as described in Section 4.10. The Investigator must follow the subject
until the AE resolves or satisfactorily stabilizes.
•
Treatment must be discontinued immediately in the event of a female subject’s
pregnancy.
•
Subject's decision to withdraw from investigational product.
•
Requirement for use of prohibited concomitant medication after consultation with the
Sponsor and Medical Monitor.
•
Subject’s repeated failure to comply with protocol requirements or study related
procedures.


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Removal of Subjects from the Study
A subject may be removed from study participation for any of the following reasons:
•
Subject death.
•
Subject's decision to withdraw from study.
•
Subject is lost to follow-up. A subject will be considered lost to follow-up after three
phone and three email attempts and documentation of a certified letter sent to the
subject’s address.
•
Termination of the study by the Sponsor, FDA, or other regulatory authorities.
Treatment Stopping Rules
If a subject has non-cutaneous adverse events of concern, clinically significant laboratory values
or any condition that the Investigator determines could possibly be related to the investigational
product, the Investigator should immediately contact the Medical Monitor to discuss if the
subject should be discontinued from treatment with investigational product.
Treatment for any individual subject will be discontinued if the subject experiences:
•
A serious adverse event (SAE) or a clinically significant non-serious AE which in the
opinion of the Principal Investigator or Medical Monitor warrants discontinuation from
the study for that subject’s well-being.
•
A treatment-emergent severe (Grade 3 or higher) laboratory abnormality (confirmed by
repeat sample).
•
A severe infection (Grade 3 or higher)
•
An Ischemic or thromboembolic cardiovascular event (regardless of Grade)
•
Any other adverse event that represents an unacceptable risk to the subject (e.g., Grade 3
or higher)
As noted above, study treatment must be discontinued immediately in the event of a female
subject’s pregnancy.
Treatment should be interrupted:
•
If a subject develops an application site reaction with the clinical appearance of an
‘irritation reaction’, and with a severity of a Dermal Response Score of 5 (erythema,
edema and papules) or greater on the scale of Berger and Bowman, treatment should be
interrupted for up to one week and may then be resumed if the reaction has, in the
opinion of the Investigator, adequately resolved.
Treatment should be discontinued:
•
If the application site reaction reoccurs, treatment should be discontinued permanently,
and the subject followed until the reaction resolves.


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For cases of suspected allergic contact dermatitis, the Medical Monitor and Sponsor should be
notified and there should be discussion about performing patch testing to further evaluate.
Patch testing is encouraged in such cases.
Phase 2b (Cohort 2)
In the event of a medical emergency where unblinding is required to provide medical care to the
subject, refer to the most current IRT plan and Breaking Treatment Codes (Section 4.6.1).
Contact the Medical Monitor and the Sponsor promptly.
Study Restrictions
Prohibitions and Concomitant Therapy
Prohibited medications and products are detailed in Table 2 (Excluded Medications and
Treatments).
Generally, the addition of new medications, including nonprescription medications, during the
course of the study is discouraged. However, the short-term use of a medication may be
authorized by the Investigator. The Investigator must make the decision to authorize the use of
any such a medication only after consideration of the clinical situation, the potential for masking
symptoms of a more significant underlying event, and whether the use of the medication will
compromise the outcome or validity of the clinical investigation. If medication is required, the
name, strength, frequency, duration of use, and reason for use will be recorded in source
documents and entered into the CRFs. Medications which have been used chronically by
subjects, in particular statins and anti-hypertensives, are allowed for use during the study,
except as prohibited in Table 2.
Table 2.
Excluded Medications and Treatments
Excluded Medications and Treatments
Washout Period from
Baseline (Visit 2)
Topical calcineurin inhibitors, PDE-4 inhibitors (Eucrisa®), topical urea-containing
emollients, topical salicylic acid-containing emollients, topical antibiotics, topical low
potency corticosteroids, topical mid potency corticosteroids
7 days
Topical high potency corticosteroids
14 days
Systemic antibiotics
14 days
Systemic non-biologic treatments for eczema (e.g., cyclosporine, azathioprine,
corticosteroids, methotrexate)
•
Oral JAK inhibitors will be allowed if stopped for reasons other than safety
concerns (28 day washout required)
28 days or 5 half-lives
(whichever is longer)
Biologics including Dupixent®
3 months or 5 half-lives
(whichever is longer)
Oral retinoids (alitretinoin/Toctino, acitretinin, isotretinoin)
3 months
Cell-depleting biologics such as rituximab
6 months


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Excluded Medications and Treatments
Washout Period from
Baseline (Visit 2)
UVB or PUVA phototherapy, tanning booths
28 days
Strong Cytochrome P-450 3A4 inhibitors and strong Cytochrome P-450 3A4 inducers
14 days
All investigational drugs
3 months (biologics); 1 month
(oral); 2 weeks (topical) - or
5 half-lives (whichever is
longer)
Note:
•
Ear drop, eye drop and nasal corticosteroid preparations are allowed.
•
Inhaled corticosteroid preparations are allowed if used for a stable condition and at a stable dose for >28 days
before Baseline (Visit 2) and are continued at the same dose throughout the study.
•
Non-medicated emollients, moisturizers and sunscreens will be allowed as normally used by the subjects.
These should not be applied to treatment sites 2 hours before or after investigational product application.
•
There is no washout for sedating or nonsedating antihistamines. During the study, systemic treatment with
sedating antihistamines is prohibited. During the study, systemic treatment with nonsedating antihistamines in a
nonstable regimen is prohibited, while systemic treatment with sedating or nonsedating antihistamines in a
stable regimen is allowed.
•
Live vaccine therapy is not allowed less than 4 weeks prior to Baseline (Visit 2).
Treatment
Investigational Product Supplies, Packaging and Labeling
Phase 1 (Cohort 1)
ARQ-252 cream 0.3% will be in 12-gram tubes. The tubes will be labeled in an open-label
manner. The tubes dispensed to a subject will be labeled with a unique number.
Phase 2b (Cohort 2)
ARQ-252 cream 0.1%, ARQ-252 cream 0.3% or vehicle formulation will be in 12-gram tubes.
The tubes will be packaged in kits, containing 2 tubes of investigational product. The number of
kits dispensed to a subject will be based on the dosing frequency, either BID (twice daily) or QD
(once daily). The kits and tubes will be labeled with a unique number, in a blinded manner.
Phase 1 and 2b (Cohorts 1 and 2)
The Sponsor will supply sufficient quantities of the investigational product to each site to allow
for completion of this study.
Records will be made of the receipt and dispensing of the investigational product supplied.
At the conclusion of the study, any unused investigational product will be returned to the
Sponsor or designee, or destroyed, as per Sponsor instructions.
Refer to the most current version of the IP Handling Plan for details on accountability, storage,
and management of IP.


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Treatment Administration
Initial treatment with the IP will occur on Day 1. At the Baseline visit the study staff will
demonstrate to the subject how to apply IP using the first tube that is assigned to the subject at
enrollment/randomization. Study site staff will demonstrate how two unit doses (two pea size
amounts of IP will cover approximately 4% BSA, i.e., both hands entirely) are properly squeezed
from the tube and applied as a thin film to cover both hands. IP will be applied to the front and
back of both hands, interlacing fingers, rubbing in thoroughly but gently, until the cream has
absorbed. The subject will then practice squeezing a similar amount and applying IP. The study
staff will confirm that the subject’s application technique is correct.
Subjects in Cohort 1 will be instructed to apply IP once daily (QD). Subjects in Cohort 2 will be
instructed to apply IP either once daily (QD) or twice daily (BID), as determined at
randomization.
IP tubes must be returned by subjects at each study visit, both empty and full, and will be
weighed. Re-training will be conducted at subsequent visits as needed (i.e., if the returned tube
weighs substantially different than the expected weight).
Subjects will be instructed to refrain from handwashing for 4 hours after IP application, if
possible. Subjects may use hand sanitizer within 4 hours of IP application, if necessary.
Hand washing and use of hand sanitizer within 4 hours of IP application will be recorded in the
subjects’ diary and CRF.
Treatment Compliance
Each IP tube will be weighed prior to dispensing at the Baseline visit and at each follow-up
clinic visit according to the Schedule of Visits and Assessments (Section 1.3). When IP is
applied in the clinic, the IP tube will be weighed before and after IP application. If the subject’s
actual use is substantially different than the expected use (see IP Handling Plan), the subject will
be retrained on the investigational product application technique.
Subjects will complete a daily diary recording the date and time of each dose applied, any missed
doses, and a comment section should the subjects have a comment, e.g., record potential AEs,
handwashing or use of hand sanitizer within 4 hours. Site personnel will review the diaries and
use the information to question the subject regarding compliance and AEs and then record
appropriate information in source documents and complete CRFs. If a subject misses a dose,
they should be instructed to return to the protocol investigational product administration schedule
(i.e., if subject forgets a dose they should wait until the next planned application and apply as
usual).
A subject will be considered compliant with the dosing regimen if the subject applies at least
80% of the expected applications during the investigational product application period and does
not miss more than 3 consecutive doses.


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Compliance will be assessed by review of the dosing diary. Weight of investigational product
applied will be measured for reporting purposes.
If the diary shows less than 80% of expected use, the subject is using too little investigational
product and retraining must be conducted and documented.
Compliance will be documented in source and in CRF.
5.
STUDY PROCEDURES
Safety Assessments
The Schedule of Visits and Assessments (Section 1.3) summarizes the clinical procedures to be
performed at each visit. Individual clinical procedures are described in detail below. Additional
evaluations/testing may be deemed necessary by the PI and/or the Sponsor for reasons related to
subject safety.
This study assesses the safety, efficacy, and PK of ARQ-252 cream 0.1%, ARQ-252 cream 0.3%
and vehicle cream. Safety will be determined by evaluating physical examinations, 12-lead
ECGs, vital signs/weight, clinical laboratory parameters, local tolerability assessments, and AEs
as outlined in the Schedule of Visits and Assessments (Section 1.3). If deemed necessary,
additional safety assessments will be performed at the discretion of the Investigator.
Screening
Before a subject’s participation in the clinical study, the Investigator is responsible for obtaining
written informed consent from the subject after adequate explanation of the study design,
anticipated benefits, and the potential risks. A subject is considered a participant of the trial once
the ICF is completely signed.
The following procedures/assessments will be performed at the Screening Visit (within 4 weeks
after signing the informed consent):
•
Review of medical and surgical history, including any history of allergies and/or contact
dermatitis
•
Review of childbearing potential (subject or partner of male subject) and contraceptive
use (see Section 5.1.2)
•
Collection of demographic data including sex, age, race, ethnicity
•
Vital signs including temperature, heart rate, and blood pressure
•
Chronic Hand Eczema assessments (BSA, IGA, HECSI).
•
Limited physical examination of skin, lungs, and heart
•
ECG


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•
Laboratory tests: hematology, chemistry, urinalysis, TSH, T4, serum pregnancy test
(for female subjects of childbearing potential), FSH (if indicated to confirm
post-menopausal status)
•
Completion of WI-NRS and NRS Pain. Subjects in Cohort 2 will also complete the
QOLHEQ.
•
Collection of concomitant medications and adverse events
Medical history of chronic hand eczema will include the following information, which will be
recorded in the CRF:
•
Morphologic subtype of HE
•
Whether the subject has ever been patch tested and if so, the patch test results and any
positives (e.g., nickel).
•
Distribution on hands (palmar vs dorsal vs interdigital vs pulpitis)
All screened subjects will receive a screening number at the time of informed consent. Subjects
in Cohort 2 will be entered into the IRT system at the time of consent.
Subjects may be re-screened one time, the original assigned Subject ID screening number will be
used for re-screening.
Contraception Requirements
Previous nonclinical research showed that the active ingredient in ARQ-252 can harm fetal
development. Subjects engaging sexual intercourse that could lead to pregnancy must adhere to
the following pregnancy testing and/or contraception requirements.
Female Subjects
Female subjects of childbearing potential (FOCBP) must have a negative serum pregnancy test at
Screening and negative urine pregnancy test at Baseline (Visit 2). For FOCBP involved in any
sexual intercourse that could lead to pregnancy: the subject must agree to use a highly effective
contraceptive method for at least 4 weeks prior to Day 1. Additionally, from Day 1 until at least
4 weeks after the last investigational product administration, these subjects must agree to use at
least 1 highly effective contraceptive method in addition to 1 barrier method of contraception.
The acceptable methods of contraception are listed below in the Figure 1.


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Figure 1.
Contraception Requirements for Female Subjects
Male Subjects:
Males, if engaging in sexual intercourse with a female who is pregnant or a female of
childbearing potential, must agree to use a condom every time during the study and every time
subsequently until 4 weeks after the last investigational product administration.
Physical Examination
Physical examinations will be performed according to the Schedule of Visits and Assessments
(Section 1.3). The physical exam will be limited to skin, lungs and heart only.
Vital Signs, Height and Weight
Vital signs will be performed according to the Schedule of Visits and Assessments (Section 1.3).
Weight, blood pressure, heart rate, and temperature will be collected in seated position after
5 mins. Subjects will be instructed to void prior to weight being taken and to remove any objects
of significant weight (i.e., jackets, outerwear, shoes, cell phones, wallet, key chains, etc.).
Height will be measured at Baseline (Day 1) only.
12-lead ECGs
12-lead ECGs will be performed according to the Schedule of Visits and Assessments
(Section 1.3).
ECGs will be obtained on subjects after 5 minutes in the supine position. All ECG tracings and
readouts will be reviewed by the Investigator and central reader at the ECG laboratory.


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Laboratory Tests
All tests listed in Table 3 below will be performed according to the Schedule of Visits and
Assessments (Section 1.3) unless otherwise noted. The collection of specimens will be in a
non-fasting state (no food restrictions). In addition, laboratory safety tests may be performed at
various unscheduled time points, if deemed necessary by the Investigator.
Table 3.
Laboratory Tests
Hematology
Serum Chemistry
•
Hemoglobin
•
Hematocrit
•
Total and differential leukocyte count
•
Red blood cell count with indices and morphology
•
Platelet count
•
Reticulocyte count1
•
Blood Urea Nitrogen
•
Bilirubin (total and direct)
•
Alkaline phosphatase
•
Aspartate aminotransferase
•
Alanine aminotransferase
•
Albumin
•
Sodium
•
Potassium
•
Chloride
•
Glucose
•
Creatinine
•
Creatine kinase
Urinalysis
Additional Tests
•
pH
•
Specific gravity
•
Protein2
•
Glucose
•
Ketones
•
Bilirubin
•
Blood2
•
Nitrite2
•
Urobilinogen
•
Leukocyte esterase2
•
Thyroid Stimulating Hormone T4 (TSH/T4)
•
Urine pregnancy test3
(for females of childbearing potential only)
•
Serum pregnancy test (hCG)4
•
Follicle-stimulating Hormone (FSH) 5
•
Pharmacokinetic (PK) assessments
1 If red blood cell count, hemoglobin or hematocrit values are below the lower limit of normal, reticulocyte count
will be performed
2 If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination (for red
blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed.
3 Cohort 1: At Baseline, Day 8, Day 15 and Day 22 for FOCBP only. Cohort 2: At Baseline, Week 4, 8, 12 and 13
for FOCBP only.
4 At screening only for FOCBP.
5 If indicated to confirm post-menopausal status


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Local Tolerability Assessment
The Investigator Local Tolerability Assessment will be performed according to the Schedule of
Visits and Assessments (Section 1.3).
Application site reactions will be graded at the timepoints outlined in the Schedule of Visits and
Assessments (Section 1.3). Irritation reactions are graded using the scale detailed in the
following section (Berger 1982). Reactions at the site of product application, which may
occur post-Baseline, should be differentiated from the preexisting inflammation associated
with the subject’s chronic hand eczema.
The Investigator assessments will be conducted by the Investigator prior to investigational
product application in the clinic.
Dermal Response
0 = no evidence of irritation
1 = minimal erythema, barely perceptible
2 = definite erythema, readily visible; minimal edema or minimal papular response
3 = erythema and papules
4 = definite edema
5 = erythema, edema and papules
6 = vesicular eruption
7 = strong reaction spreading beyond application site
Other Effects
A = slight glazed appearance
B = marked glazing
C = glazing with peeling and cracking
D = glazing with fissures
E = film of dried serous exudates
F = small petechial erosions and/or scabs
G = no other effects
The Subject Local Tolerability Assessment will be performed according to the Schedule of Visits
and Assessments (Section 1.3).
This assessment will be administered by the site 10 to 15 minutes after investigational product
application in the clinic.


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Grade
Sensation Following Investigational Product Application
0 (none)
No sensation
1 (mild)
Slight warm, tingling sensation; not really bothersome
2 (moderate)
Definite warm, tingling sensation that is somewhat bothersome
3 (severe)
Hot, tingling/stinging sensation that has caused definite discomfort
Adverse Events
Adverse events (AEs) will be collected continuously during the study beginning at informed
consent and assessed according to the Schedule of Visits and Assessment (Section 1.3).
Any treatment emergent AEs will be followed in the clinic for up to one month at the
Investigator’s discretion until resolved or otherwise judged as clinically stable.
For further details on Adverse Events please see Section 5.7.
Efficacy Evaluations
Investigator’s Global Assessment (IGA)
Investigator’s Global Assessment of chronic hand eczema will be performed according to the
Schedule of Visits and Assessments (Section 1.3).
The IGA is a static evaluation of qualitative overall chronic hand eczema severity. This global
assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4).
Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions
that minimizes inter-observer variability.
Every effort must be made for the same Evaluator to complete the IGA for the subject at
every study visit.
IGA will be assessed at clinic visits prior to the subject applying Investigational Product
and other physician assessments.


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Investigator Global Assessment of Disease (IGA)
Score
Grade
Description
0
Clear
Absence of erythema and scaling,
AND
Absence of vesiculation, edema, and fissures.
Note: Post-inflammatory pigmentary changes may be present.
1
Almost clear
Barely perceptible or faint erythema, and/or
Slight flaking over limited areas, mostly fine scales,
AND
Absence of vesiculation, edema, or fissures
2
Mild
Barely perceptible or faint erythema, and/or
Slight flaking over limited areas, mostly fine scales
AND
Scattered vesicles affecting up to 10% of hand, without erosion, and/or
Dermal swelling over less than 10% of hands, and/or
Cracked skin affecting a small area of the hand
3
Moderate
Either barely perceptible or faint erythema, or prominent redness, and/or
Either slight flaking over limited areas, mostly fine scales, or flaking over widespread
area(s), coarser scale
AND
Scattered or clustered vesicles affecting up to 30% of hand, without visible erosion or
excoriation, and/or
Definite dermal swelling over more than 10% of hand, and/or
Cracked skin affecting multiple areas of the hand
4
Severe
Either prominent or deep intense red color, and/or
Either flaking over widespread area(s), coarser scales, or desquamation covering over
30% of the hand, with coarse thick scales
AND
At least one of the following:
High density of vesicles extending over large area(s), or with erosion or excoriation,
and/or
Dermal swelling with skin induration over widespread area(s), and/or
One or more deep fissures and causing bleeding
Adapted from Ruzicka 2008.


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Body Surface Area (BSA)
BSA Assessments will be performed according to the Schedule of Visits and Assessments
(Section 1.3).
The BSA affected by chronic hand eczema will be determined by the subject’s hand method,
where the subject’s hand (including fingers) surface area is assumed to equal 1% of body surface
area (BSA). Lesions on both hands will be added together. Affected areas of the lateral aspects
of the fingers and hands should be assigned to the palmar surface.
Worst Itch Numerical Rating Scale (WI-NRS)
Subjects will complete the WI-NRS pruritus assessment. WI-NRS Assessments will be
performed according to the Schedule of Visits and Assessments (Section 1.3).
Subjects will complete the WI-NRS pruritis assessment in the clinic during Screening and then
daily at home from the Baseline/Day 1 visit until the last visit. Subjects will record their
WI-NRS on a diary and will return the diary to the clinic at each visit. Sites will review WI-NRS
entries and enter into the CRF.
The WI-NRS has been developed as a simple, single item to assess the patient-reported severity
of this symptom at its highest intensity during the previous 24-hour period. (Naegeli 2015).
The WI‑NRS will be determined by asking the subject’s assessment of worst itch over the past
24 hours. The scale is from ‘0 to 10’ (“no itch” to “worst imaginable itch”).
Copyright © (2017) Eli Lilly and Company. All rights reserved.
NRS-Pain Scale
The Numerical Rating Scale (NRS) for Pain will be performed according to the Schedule of
Visits and Assessments (Section 1.3).
Subjects will complete the NRS Pain assessment in the clinic during screening and then daily at
home from the Baseline/Day 1 visit until the last visit. Subjects will record their NRS-Pain score
on a diary and will return the diary to the clinic at each visit. Sites will review NRS-Pain entries
and enter into the CRF.


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The NRS-Pain Scale is the most widely used instrument for pain screening. Subjects will select
the number between 0 and 10 that fits best to their worst pain intensity over the past 24 hours,
where 0 represents ‘no pain at all’ and 10 ‘the worst pain possible’.
Source: https://www.physio-pedia.com/images/4/47/NRS_pain.jpg
HECSI
The Hand Eczema Severity Index (HECSI) will be performed according to the Schedule of Visits
and Assessments (Section 1.3).
HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand
eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total
HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and
a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100%
affected area).
Clinical Signs
Fingertips
Fingers
(except tips)
Palm of
hands
Back of
hands
Wrists
Erythema (E)
Infiltration/papulation (I)
Vesicles (V)
Fissures (F)
Scaling (S)
Oedema (O)
SUM (E + I + V + F + S + O)
Extent (Ex)
Total HESCI Score =
Sum x Ex +
Sum x Ex +
Sum x Ex +
Sum x Ex +
Sum x Ex +
Total HECSI score (min 0; max 360). For each location (total of both hands) the affected area was given a score
from 0 to 4: (0, 0%; 1, 1-25%; 2, 26-50%; 3, 51-75%; 4, 76-100%) for the extent of clinical symptoms. Finally the
score given for the extent for each location was multiplied by the total sum of the intensity of each clinical feature
(each contributing equally to the final score) and the total sum called the HESCI score was calculated, varying from
0 to a maximum severity score of 360 points.
Adapted from Held 2005.


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Quality of Life in Hand Eczema Questionnaire
The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) will be performed according to
the Schedule of Visits and Assessments (Section 1.3) in Phase 2b (Cohort 2). The QOLHEQ is
an instrument to assess disease specific Health Related Quality of Life (HRQOL) in patients
suffering from hand eczema (Appendix 1). The construct HRQOL includes all impairments or
limiting conditions caused by the health state of an individual. The QOLHEQ is a disease
specific instrument, thereby only assessing impairments caused by hand eczema. It consists out
of 30 items which can be summarized according to four domains of HRQOL: Impairments
because of (1) symptoms, (2) emotions, (3) limitations in functioning or (4) because of treatment
and prevention.
Nail Dystrophy Assessment
Phase 2b (Cohort 2)
A Nail Dystrophy Assessment will be performed in Cohort 2 according to the Schedule of Visits
and Assessments (Section 1.3) to identify any alteration of nail morphology. Assessment to
include the following evaluations by the Investigator:
Baseline/Day 1:
•
Does the subject have at least one nail with significant dystrophy extending to the
cuticle? Yes/No
•
If “Yes”, record which nail has the worst dystrophy (indicating left or right)
Subsequent visits according to the Schedule of Visits and Assessments:
•
For the identified fingernail with the worst dystrophy at Baseline/Day 1, is there normal
appearing nail distal to the cuticle, Yes/No
•
If “Yes”, how many millimeters of normal appearing nail distal to the cuticle?
Sites participating in optional photography will obtain photos of nail with the worst dystrophy at
Baseline/Day 1 and at subsequent visits according to the Schedule of Visits and Assessments
(Section 1.3) and Section 5.3.2.
Other Evaluations
Pharmacokinetics Assessment
PK draws will be performed according to the Schedule of Visits and Assessments (Section 1.3)
for all subjects at all sites.
Phase 1 (Cohort 1)
•
Serial PK sampling will be performed on Day 1 (1, 2, 4, 6, and 24 hours post-dose
administration), and at Day 15 (pre-dose and 1, 2, 4, 6, and 24 hours post-dose
administration). For 24-hour timepoints, subjects return to the clinic on the following day


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within 2 hours of the IP application time from the previous day for PK plasma sample
collection. A pre-dose/trough PK sample will be taken at Day 8.
Phase 2b (Cohort 2):
•
PK will be evaluated through trough/pre-dose sampling at Baseline, Day 29, and Day 85.
PK draws will be collected while the subject is having serum chemistries drawn at applicable
visits. The draws will be pre-dose investigational product application in the clinic. Ensure
investigational product is not applied in the area where PK will be drawn.
Medical Photography
Phase 2b (Cohort 2)
Photography will be performed at selected investigational sites using Canfield photography
equipment according to the Schedule of Visits and Assessment (Section 1.3) in Phase 2b
(Cohort 2). Photography will be optional. All efforts will be made to de-identify the subjects.
Sites participating in optional photography will obtain photos of nail with the worst dystrophy at
Baseline/Day 1 and at subsequent visits according to the Schedule of Visits and Assessments
(Section 1.3).
Final Study Visit – End of Study
Phase 1 (Cohort 1)
The approximate final study visit will occur at Week 3 (Day 22).
Phase 2b (Cohort 2):
The approximate final study visit will occur at Week 13 (Day 92).
For both Cohorts, the procedures performed during these visits are as described in the Schedule
of Visits and Assessments (Section 1.3). A 3-day scheduling window is allowed for this visit.
Adverse events will be recorded as reported by the subject and followed to resolution
(as necessary).
Early Termination Visit
If a subject is withdrawn or wishes to exit the study prior to the final study visit, an early
termination visit will be scheduled. This visit should include the procedures and assessments that
would be performed at the final study visit for either Cohort 1 or Cohort 2 (Section 1.3).
Unscheduled Visit
Unscheduled visits may be necessary to repeat testing following abnormal laboratory results, for
follow-up of AEs, or for any other reason, as warranted in the judgement of the Investigator.


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The following information will be collected for all subjects:
•
Concomitant medications/procedures
•
AEs
•
BSA, IGA, HESCI
Adverse Events
Adverse Event Definition
An AE means any untoward medical occurrence associated with the use of a drug in humans,
whether or not considered drug related. An AE can therefore be any unfavorable and unintended
sign (including an abnormal laboratory finding), symptom, or disease temporally associated with
the use of a medicinal (investigational) product, whether or not related to the medicinal
(investigational) product.
AEs will be collected following informed consent of the subject through subject study
completion.
A treatment emergent adverse event (TEAE) is defined as an AE that started post application of
investigational product through study completion.
Application site reactions will be considered adverse events if they require intervention,
suspension or discontinuation of investigational product.
Serious Adverse Event Definition
The definitions and reporting requirements of Health Canada/the Food and Drug Administration
(FDA)/ Therapeutic Goods Administration (TGA)/ICH Guidelines for Clinical Safety Data
Management, Definitions and Standards for Expedited Reporting, Topic E2A will be adhered to.
If any AEs are serious, as defined by ICH Guidelines for Clinical Safety, required procedures
will be followed.
All SAEs will be reported to the Sponsor (or delegate) via fax or e-mail within 24 hours of
becoming aware of the event, whether or not the serious events are deemed IP-related.
All serious event reporting will adhere to ICH E6: Guideline for Good Clinical Practice and
ICH E2A: Clinical Safety Data Management: Definitions and Standards for Expedited
Reporting.: The ERB/IRB will be notified of the Alert Reports as per HC, FDA, ICH and the
IRB/ERB’s policies and procedures. Refer to the Safety Reporting Instructions for SAE
reporting.
An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following
outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing
hospitalization, a persistent or significant incapacity or substantial disruption of the ability to
conduct normal life functions, or a congenital anomaly/birth defect. Important medical events
that may not result in death, be life-threatening, or require hospitalization may be considered
serious when, based upon appropriate medical judgment, they may jeopardize the subject and


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may require medical or surgical intervention to prevent one of the outcomes listed in the above
definition. Examples of such medical events include allergic bronchospasm requiring intensive
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in
inpatient hospitalization, or the development of drug dependency or drug abuse.
Life-threatening is defined as an AE that in the view of the PI or Sponsor, places the subject at
immediate risk of death. It does not include an AE that, had it occurred in a more severe form,
might have caused death.
Hospitalization does not include the following:
•
Rehabilitation facilities, hospice facilities or respite care (e.g., caregiver relief)
•
Nursing homes or skilled nursing facilities
•
Emergency room visits
•
Same day surgeries (as outpatient/same day/ambulatory procedures)
•
<24 hour admissions for observation or evaluation
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is
not in itself an SAE. Examples include:
•
Admission for treatment of a preexisting condition that did not worsen
•
Hospitalizations for cosmetic elective surgery, social, and/or convenience admissions
•
Pre-planned treatments or surgical procedures should be noted in the history
documentation for the individual subject.
•
Diagnostic and therapeutic procedures, such as surgery, should not be reported as AEs;
however, the medical condition for which the procedure was performed should be
reported if it occurs during the reporting period and meets the definition of an AE. For
example, an acute appendicitis that begins during the AE reporting period should be
reported as an AE, and the resulting appendectomy should be recorded as treatment of the
AE.
Unexpected is defined as an AE that is not listed in the IB or is not listed at the specificity or
severity that has been observed; or is not consistent with the risk information described in the
general investigational plan or elsewhere in the current study documentation.
If a SAE occurs to a subject on this study, contact the Medical Monitor within one business day
of knowledge of event.
Suspected Unexpected Serious Adverse Reaction (SUSAR)
This is defined as a serious adverse reaction, the nature or severity of which is not consistent
with the known study treatment information. A serious event or reaction is not defined as a
SUSAR when: ‘it is serious but expected’ or it does not fit the definition of an SAE, whether
expected or not.


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Safety Review with Subject
At each follow-up visit, subjects will be queried with an open-ended question such as:
‘How have you been feeling since your last visit?’ Additionally, the study staff will review
subject diaries and, if it appears that a potential AE was recorded, study staff will query the
subject and determine if an AE occurred.
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s)
will be evaluated by the PI and treated and/or followed up for up to one month after end of
treatment until the symptoms or value(s) return to normal, or acceptable levels, as judged by the
PI.
Where appropriate, medical test(s) and/or examination(s) will be performed to document
resolution of event(s). Outcome may be classified as resolved, improved, unchanged, worse, fatal
or unknown (lost to follow-up).
Adverse Event Reporting
AEs will be collected following informed consent of the subject through subject study
completion.
The Investigator will review each event and assess its relationship to investigational product
treatment (unrelated, unlikely, possibly, probably, likely). Each sign or symptom reported will be
graded on the NIH NCI CTCAE (Version 5.0) toxicity grading scale 5-point severity scale
(Grade 1, 2, 3, 4 and 5). The date and time of onset, time relationship to drug dosing, duration,
and outcome (resolved, improved, unchanged, worse, fatal, or unknown/lost to follow-up) of
each event will be noted.
The relationship of each AE to the investigational product will be assessed using the following
definitions:
Unrelated
•
The AE must clearly be caused by the subject’s clinical state, or the study
procedure/conditions.
•
Definitely not related to drug.
•
Temporal sequence of AE onset relative to administration of drug not reasonable.
•
Another obvious cause of an AE.
Unlikely
•
Time sequence is unreasonable.
•
There is another more likely cause for an AE.
Possibly
•
Corresponds to what is known about the drug.
•
Time sequence is reasonable.
•
Could have been due to another equally, likely cause.
Probably
•
Is a known effect of the drug.
•
Time sequence from taking drug is reasonable.
•
Ceases on stopping the drug.
•
Cannot be reasonably explained by the known characteristics of the subject’s clinical state.
Likely
•
Is a known effect of the drug (e.g., listed in Physicians' Desk Reference, Compendium of
Pharmaceuticals and Specialties, IB).
•
Time sequence from taking drug is reasonable.
•
Event stops upon stopping drug, event returns upon restarting drug.


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The following CTCAE toxicity grading scale 5-point severity scale definitions for rating
maximum severity will be used:
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.*
Grade 3
Severe or medically significant but not immediately life-threatening; Hospitalization or
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living.**
Note: An experience may be severe but may not be serious, e.g., severe headache).
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
Note: A semi-colon indicates ‘or’ within the description of the grade.
*Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the
telephone, managing money, etc.
**Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking
medications, and not bedridden.
AEs will be coded using the most current MedDRA® version available at the start of the study
(e.g., 21.0 or higher).
Reporting Pregnancy
During the study, all subjects should be instructed to contact the Investigator immediately if they
suspect they might be pregnant (e.g., missed or late menstrual period). If pregnancy is
confirmed, Investigational Product must be discontinued immediately, the subject should be
referred to an obstetrician experienced in reproductive toxicity for evaluation and counseling,
and the subject should be followed until conclusion of the pregnancy. Subject may be required to
sign a separate informed consent form to obtain pregnancy follow-up information, per local
requirements.
The Investigator is responsible for reporting all available pregnancy information on the
pregnancy report and submitting to the Medical Monitor within 24 hours of becoming aware of
the event, although pregnancy itself is not considered an AE. Follow-up information detailing
the outcome of the pregnancy and the health of the newborn should be reported as it becomes
available. Any pregnancy resulting in a congenital abnormality or birth defect of the newborn,
or neonatal death occurring within 30 days of the birth must be reported as a SAE, regardless of
causality. Any infant death that occurs after the 30 day reporting period that the Investigator
suspects is related to Investigational Product must also be reported as an SAE.
Partner pregnancies of a male subject will be reported.


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6.
DATA ANALYSIS
Data will be handled and processed according to the Contract Research Organization’s Standard
Operating Procedures, which are written based on the principles of GCP.
Statistical Methods
The methodology presented below is a summary of the more detailed analysis plan that will be
presented in the Statistical Analysis Plan (SAP). The SAP will be finalized before the database
is locked and unblinded. Any changes to the methods described in the final SAP will be
described and justified in the clinical study report.
All statistical processing will be performed using SAS® (Version 9.4) unless otherwise stated.
Descriptive statistics will be used to provide an overview of the safety, efficacy, and
pharmacokinetic results. For categorical parameters, the number and percentage of subjects in
each category will be presented. The denominator for percentage will be based on the number of
subjects appropriate for the purpose of analysis. For continuous parameters, descriptive statistics
will include n (number of subjects), mean, standard deviation (SD), median, minimum,
and maximum.
Missing efficacy data for IGA will be imputed using multiple imputation.
The primary statistical comparisons and secondary endpoints will be made at the
0.10 significance level and will not be adjusted for multiple comparisons.
Determination of Sample Size
Cohort 1 will include approximately 6 evaluable subjects, which is deemed adequate for the
purpose of evaluating safety and PK prior to Cohort 2.
There are approximately 215 subjects planned for Cohort 2. Approximately 61 subjects will
receive ARQ-252 cream 0.3% QD, approximately 61 subjects will receive ARQ-252 cream 0.3%
BID, approximately 31 subjects will receive ARQ-252 cream 0.1% QD, approximately 31
subjects will receive matching vehicle cream QD, and approximately 31 subjects will receive
vehicle cream BID. The randomization scheme will be 2:2:1:1:1 between these 5 treatment
groups, stratified by study site and IGA at Baseline.
The primary statistical comparisons will be to assess the ARQ-252 cream 0.3% group BID group
versus the vehicle BID group, to assess the ARQ-252 cream 0.3% QC group versus the vehicle
QD group, and to assess the ARQ-252 cream 0.1% QD group versus the vehicle QD group.
A sample size of 55 per active arm and 28 per vehicle arm will provide approximately 85%
power at the 2-sided 10% significance level to detect a difference in the rate of subjects attaining
an IGA score of clear or almost clear (for each ARQ-252-treated group versus vehicle group
within the same daily dosing frequency), assuming an active treatment response rate of 45% and
a vehicle response rate of 15%. This is based on a 2-group X2 test of equal proportions
(without continuity correction). With a 10% dropout rate, the sample size for the study would be
increased to 61 subjects per active arm and 31 subjects per vehicle arm (215 subjects total).


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The primary statistical comparisons and evaluations of secondary endpoints will not be adjusted
for multiplicity.
Subjects to Analyze
Five analysis populations will be defined:
•
The Safety population will include all subjects who are enrolled and received at least one
confirmed dose of study medication. This population will be used for all safety analyses
and will be defined separately for each Cohort.
•
The Intent-to-Treat will include all subjects randomized to Cohort 2. This population
will be the primary analysis for the analysis of efficacy endpoints.
•
The Per-Protocol Population will include all subjects in the safety population, who were at
least 80% compliant with study medication application, and showed no important
deviations from the study protocol that would affect the interpretation of efficacy.
This population will be used as a sensitivity analysis of primary and secondary efficacy
endpoints.
•
The Pruritis population is a subset of the ITT population and include subjects with
WI‑NRS score ≥4 at Baseline. This population will be used for the analysis of WI-NRS.
•
The PK population will include all subjects receiving the active drug with sufficient
plasma concentrations of SHR0302 to define a profile, as determined by the
pharmacokineticist.
Interim Analysis
No interim efficacy analyses are planned. Safety data will be reviewed on an ongoing basis.
Background and Demographic Characteristics
Demographics, baseline disease characteristics, baseline height, weight, and BSA will be
summarized descriptively for all enrolled (Cohort 1) and randomized (Cohort 2) subjects.
Study Disposition
The number of subjects randomized, receiving IP, completing study, and withdrawing
prematurely (with reason for withdrawal) will be summarized by cohort and treatment group.
Protocol Deviations and Eligibility Deviations
The number of subjects with important protocol deviations and/or eligibility deviations will be
summarized by category and by treatment group.


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Investigational Product Compliance
The number of IP applications by each subject based on diary data will be summarized using
descriptive statistics. The amount of IP used by each subject based on product weight will be
summarized by treatment using summary statistics (mean, SD, median, minimum, and
maximum), and categorically. IP compliance will be calculated based on number of applications
divided by the expected number (amount) of IP for each subject. Compliance will be
summarized descriptively by cohort and treatment group.
Efficacy Evaluation
Primary Efficacy Endpoint
The primary efficacy endpoint is the rate of subjects achieving an IGA score of ‘clear’ or ‘almost
clear’ at Week 12.
The primary statistical comparisons will be to assess the ARQ-252 cream 0.3% group BID group
versus the vehicle BID group, to assess the ARQ-252 cream 0.3% QD group versus the vehicle
QD group, and to assess the ARQ-252 cream 0.1% QD group versus the vehicle QD group.
The primary endpoint will be analyzed using a Cochran-Mantel-Haenszel test stratified by IGA
at Baseline and study site. Statistical significance will be concluded at the 2-sided 10%
significance level for each of the primary comparisons. Missing scores will be imputed using
multiple imputation.
Secondary Endpoints
The Secondary Efficacy Endpoints will include:
•
The rate of achievement of IGA of ‘clear’ or ‘almost clear’ PLUS at least a 2-point
improvement from Baseline at Weeks 2, 4, 8 and 12
•
The rate of achievement of at least a 2-point improvement from baseline at Weeks 2, 4, 8
and 12
•
The rate of achievement of IGA of ‘clear’ or ‘almost clear’ at Weeks 2, 4, and 8
•
Time to IGA of ‘clear’ or ‘almost clear’
•
Change in IGA score at Weeks 2, 4, 8, and 12 as compared to Baseline
•
Change in WI-NRS pruritus score at Weeks 2, 4, 8, and 12 as compared to Baseline
•
The rate of achievement of ≥4-point reduction from Baseline in WI-NRS pruritus score at
Weeks 2, 4, 8, and 12, in subjects with Baseline WI-NRS pruritus score of at least 4
•
Time to the first achievement of ≥4-point reduction from Baseline in WI-NRS pruritus
score in subjects with Baseline WI-NRS pruritus score of at least 4
•
Percent change in HECSI (Hand Eczema Severity Index) score at Weeks 2, 4, 8, and 12
compared to Baseline


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•
Change in Pain NRS score from Baseline to Weeks, 2, 4, 8, and 12
•
The rate of achievement of ≥4-point reduction from Baseline in Pain NRS score at
2 weeks, 4 weeks, 8 weeks, and 12 weeks in subjects with Baseline Pain NRS score of at
least 4
•
Time to the first achievement of ≥4-point reduction from Baseline in Pain NRS score in
subjects with Baseline Pain NRS score of at least 4
•
Change from Baseline in overall Quality of Life in Hand Eczema Questionnaire
(QOLHEQ) score at each visit.
•
Percent BSA affected by disease and % change from baseline in BSA affected by disease
at baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Exploratory Endpoints
•
Change from Baseline in Nail Dystrophy at each visit (Cohort 2 only)
The binary secondary endpoints will be analyzed using a Cochran-Mantel-Haenszel test stratified
by Baseline IGA and study site as with the primary endpoint. The continuous secondary
endpoints will be analyzed using an analysis of covariance stratified by Baseline IGA and study
site and Baseline values of the endpoint as independent variables. Statistical comparison
between the active treatment arm and vehicle arm will be facilitated by using contrasts.
Analyses may also include pooling the active treatment groups together for comparison against
the vehicle treatment groups; specifications for these analyses will be included in the SAP.
Safety Analysis
Descriptive statistics will be calculated for safety data and presented by visit and treatment group
for quantitative safety data and frequency counts will be compiled for classification of qualitative
safety data. Summaries of local tolerability will be presented by visit and treatment group.
Adverse Events
All treatment-emergent AEs occurring during the study will be recorded and classified on the
basis of MedDRA terminology for the safety population. Treatment-emergent AEs are those AEs
with an onset on or after the date of study treatment. All treatment-emergent AEs will be
summarized by treatment group, the number of subjects reporting treatment-emergent AEs,
system organ class, preferred term, severity, relationship, and seriousness. Serious adverse events
(SAEs) will be listed by subject. SAEs will be summarized by treatment group, severity, and
relationship to study treatment. For AEs, each subject will be counted only once within a system
organ class or a preferred term using the event with the greatest relationship and greatest
severity.
All information pertaining to AEs noted during the study will be listed by subject, detailing the
verbatim description given by the Investigator, preferred term, system organ class, start date,
stop date, severity, action taken regarding IP, corrective treatment, outcome, and IP relatedness.
The event onset will also be shown relative (in number of days) to date of first application.


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In addition, a listing of subjects who prematurely discontinue from the IP due to adverse events
will also be provided.
Local Tolerance Assessment
For the Investigator’s and Subject’s assessment, the numeric application site reaction scores will
be summarized individually by using number and percentage of subjects by visit, as well as
mean/median scores.
Medical History and Physical Examinations
Clinically significant changes observed during physical examination will be captured as adverse
events and included in AE tabulations.
Clinical Laboratory Results and Vital Signs
All clinical laboratory results and ECG measurements and their change from Baseline (pre-dose),
will be summarized descriptively by parameter, along with time point of collection.
A shift table describing out-of-normal range shifts will be provided for clinical laboratory results.
Prior and Concomitant Medications
Prior and concomitant medication information for all enrolled/randomized subjects will be
presented in electronic datasets. Summary tables will be presented by World Health
Organization-Anatomical Therapeutic Chemical Classification System (WHO-ATC) therapeutic
category and product.
Pharmacokinetic Analysis
Plasma drug concentrations at pre-dose will be summarized using descriptive statistics.
A manual for blood sampling, collection, processing, and sample shipment will be provided in a
separate document.
A detailed description of the PK analysis will be presented in the SAP.
7.
STUDY ADMINISTRATION
Ethics
Ethics Review Board
Before enrollment of subjects into the study, the current protocol and ICF will be reviewed and
approved by an appropriate IRB or IEC, as required by FDA (21 CFR § 56), Health Canada, ICH
GCP regulations and other local/regional regulatory requirements. A letter documenting the IRB
or IEC approval must be received by the Sponsor (or delegate) before the initiation of the study


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at a clinical site. Amendments to the protocol will be subject to the same requirements as the
original protocol.
The Investigator, Sponsor, or designee will submit a progress report at least once yearly to the
IRB or IEC. However, the frequency of these reports will depend on IRB or IEC requirements.
As soon as possible after completion or termination of the study, the Investigator will submit a
final report to the IRB or IEC per the IRB or IEC requirements, and in compliance with FDA,
Health Canada, local and regional regulations and ICH GCP guidelines.
The Investigator, the Sponsor, or designee shall promptly notify the IRB or IEC of any SAEs,
SUSARs, or any other information that may affect the safe use of the investigational products
during the study, per the IRB or IEC local requirements, and in compliance with FDA and Health
Canada regulations and ICH GCP guidelines.
Ethical Conduct of the Study
This research will be carried out in accordance with the protocol, the principles of the
Tri-Council Policy Statement (TCPS), the ethical principles set forth in the Declaration of
Helsinki, and the ICH harmonized tripartite guideline regarding GCP (E6 (R2), Nov 2016) and
the applicable regulations of the country(ies) in which the trial is conducted.
Subject Information and Consent
The purpose of the study, the procedures to be carried out and the potential hazards will be
described to the subjects in non-technical terms. Subjects will be required to read, sign and date a
current version of the IRB/EC approved ICF summarizing the discussion prior to enrollment and
will be assured that they may withdraw from the study at any time without jeopardizing their
medical care.
Subjects will be given a signed copy of their ICF.
Study Completion and Termination
Study Completion
The study is considered completed with the last visit of the last subject participating in the study.
The final data from the investigational site will be sent to the Sponsor (or designee) after
completion of the final subject visit at that site, in the time frame specified in the Clinical Trial
Agreement.
Study Termination
The Sponsor reserves the right to close the investigational site or terminate the study at any time
for any reason at the sole discretion of the Sponsor. Investigational sites will be closed upon
study completion. An investigational site is considered closed when all required documents and
study supplies have been collected and a site closure visit has been performed. The Investigator
may initiate site closure at any time, provided there is reasonable cause and sufficient notice is
given in advance of the intended termination.


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Reasons for the early closure of an investigational site by the Sponsor or Investigator may
include but are not limited to:
•
Failure of the Investigator to comply with the protocol, the Sponsor’s procedures, or GCP
guidelines.
•
Inadequate recruitment of subjects by the Investigator.
•
Discontinuation of further IP development
Study Monitoring
Prior to the initiation of the clinical investigation, Sponsor representatives or designees will visit
the clinical site where the investigation is to be conducted. Sponsor representatives shall ensure
that the Investigator understands the investigational status of the investigational product, all
requirements of the investigation to be undertaken, and all of his/her responsibilities as an
Investigator. Sponsor representatives will also visit the clinical site at appropriate intervals as
required to ensure compliance with the protocol and to verify the accuracy and completeness of
data reported on the CRFs. The Study Director or designees shall be available for consultation
with the Investigator and serve as liaisons between the clinical site and the Sponsor.
The Sponsor or authorized designees may inspect all documents and records required to be
maintained by the Investigator, including but not limited to medical records (office, clinic, or
hospital) and investigational product dispensation logs for the subjects in this clinical
investigation. The Investigator must permit access to such records. The Investigator must
obtain, as part of informed consent, permission for an authorized representative of the Sponsor,
or regulatory authorities, to review, in confidence, any records identifying subjects.
Data Quality Assurance
In order to ensure the collection of accurate, consistent, complete, and reliable data during this
clinical study, Sponsor representatives or designees may conduct audits of participating clinical
study sites at appropriate intervals throughout the study. The results of these periodic clinical
study site audits may be subject to review by independent auditors at completion of the clinical
investigation.
The Clinical Study Report will undergo QC review by the Clinical Research Organization’s
Quality Assurance (QA) department.
All clinical data will undergo a quality control check prior to clinical database lock. Edit checks
are performed for appropriate databases as a validation routine to check for missing data,
data inconsistencies, data ranges etc. Corrections are made prior to database lock.
Data Handling and Record Keeping
During the clinical study, the Investigator will maintain adequate records, including medical
records, records detailing the progress of the study for each subject, laboratory reports, signed
informed consent forms, investigational product disposition records, correspondence with the


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ERB/IRB and Study Monitor/Sponsor, AE reports, and information regarding subject
discontinuation and completion of the clinical investigation.
All required study data will be recorded on CRFs. Any change of data will be recorded on the
audit trail and a reason for the change will be entered.
The Principal Investigator must retain all documentation relating to the study for a period of at
least 2 years after the last marketing application approval or, if not approved, 2 years following
the discontinuance of the test article for investigation. If this requirement differs from any local
regulations, the local regulations will take precedence unless the local retention policy is less
than 2 years.
Protocol Amendments and Deviations
No change or amendment to this protocol may be made by the Investigator or Sponsor after the
protocol has been agreed to and signed by all parties unless such change(s) or amendment(s) has
(have) been agreed upon by the Investigator and Sponsor. Any change agreed upon will be
recorded in writing, and the written amendment will be signed by the Investigator and Sponsor.
Institutional review board approval is required prior to the implementation of an amendment,
unless overriding safety reasons warrant immediate action, in which case the IRB(s) will be
promptly notified.
No deviation from the protocol will be made except to protect the life or physical well-being of a
subject in an emergency. Except in such emergencies, prior approval of the Sponsor, and the
IRB, is required before deviations from the planned protocol. All protocol deviations that occur
during the study will be documented and reported to Sponsor and to the IRB(s), if applicable,
according to regulations. Further details about the documentation, evaluation, and follow-up of
protocol deviations are detailed in this study’s clinical monitoring plan.
No waivers to inclusion/exclusion criteria will be granted; subjects need to meet all criteria,
exactly as specified, to be enrolled. Additionally, prospective deviations from the protocol or
investigational plan are not permitted except to protect the life or physical well-being of a subject
in an emergency. Deviations that occur unintentionally or are the result of action by the subject
must be documented and reported to the IRB(s), if applicable, according to regulations. Further
details about the documentation, evaluation, and follow-up of protocol deviations are detailed in
this study’s clinical monitoring plan.
Confidentiality and Privacy
The Investigator must assure that subjects’ anonymity will be strictly maintained and that their
identities are protected from unauthorized parties. Only an identification code and any other
unique identifier(s) as allowed by local law (such as date of birth) will be recorded on any form
or biological sample submitted to the Sponsor.


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Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
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Page 67 of 72
The Investigator agrees that all information received from Arcutis Biotherapeutics, Inc.,
including but not limited to the Investigator’s Brochure, this protocol, CRF/eCRF, the IP, and
any other study information, remain the sole and exclusive property of Arcutis Biotherapeutics,
Inc. during the conduct of the study and thereafter. This information is not to be disclosed to any
third party (except employees or agents directly involved in the conduct of the study or as
required by law) without prior written consent from Arcutis Biotherapeutics, Inc. The
Investigator further agrees to take all reasonable precautions to prevent the disclosure by any
employee or agent of the study site to any third party or otherwise into the public domain.
Conflict of Interest
All study investigators will provide documentation of their financial interest or arrangements
with Arcutis Biotherapeutics, Inc., or proprietary interests in the investigational product under
study. This documentation must be provided prior to the Investigator’s participation in the study.
All investigators with reported conflict of interest will be required to have such conflicts
managed in a way that is appropriate to their participation in the design and conduct of this
study.
Report Format
According to the ICH Harmonized Tripartite Guideline (Organization of the Common Technical
Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH M2 Expert
Working Group), the final report will be written according to the ICH E3 Guideline (Structure
and Content of Clinical Study Reports).
Publication Policy
The Sponsor is supportive of publishing clinical trial findings. Any form of publication that is
derived from this study must be submitted to Arcutis Biotherapeutics, Inc. for review and
approval. The process of coordinating publication efforts is detailed in the Clinical Trial
Agreement.


Protocol ARQ-252-205
Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
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Page 68 of 72
8.
REFERENCES
Berger RS, Bowman JP. A reappraisal of the 21-day Cumulative Irritation Test in man.
J. Toxicol Ot & Ocular Toxicol. 1982:1(2);109-115.
Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa
randomized trial. Br J Dermatol. 2016a;175(5):902-911.
Diepgen T, Andersen K, Brandao F, et al. Hand eczema classification: a cross‐sectional,
multicentre study of the aetiology and morphology of hand eczema. British Journal of
Dermatology.2009;160:353-358. doi:10.1111/j.1365-2133.2008.08907.x.
Gooderham n T, Andersen K, Brandao F, et al. Hand eczema classification: a cross‐sectional,
multicentre study of the aetiology and morphology of hand eczema. British Journal of
Dermatology. 2009;160: 353-358. doi:10.1111/j.1365-2133.2008.08907.x.
Gooderham MJ, Forman SB, Bissonnette R, et al. Efficacy and safety of oral Janus kinase 1
inhibitor abrocitinib for patients with atopic dermatitis a phase 2 randomized clinical trial.
JAMA Dermatol. 2019; 155(12):1371-1379.
Guttman-Yassky E, Thaçi D, Pangan A, at al. Upadacitinib in adults with moderate to severe
atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. Journal of
Allergy and Clinical Immunology. 2019a Nov 28, doi: 10.1016/j.jaci.2019.11.025 [article in
press].
Guttman-Yassky E, Silverberg JI, Nemoto O, et al. Baricitinib in adult patients with moderate-
to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled
multiple-dose study. J Am Acad Dermatol. 2019b Apr, 80(4):913-921,
doi:10.1016/j.jaad.2018.01.018.
Halling-Overgaard AS, Kezic S, Jakasa I, et al. Skin absorption through atopic dermatitis skin: a
systematic review. Br J Dermatol. 2017;177: 84-106.
Held E, Skoet R, Johansen J, et al. The hand eczema severity index (HECSI): a scoring system
for clinical assessment of hand eczema. A study of inter- and intraobserver reliability.
Br J Dermatol. 2005 Feb;152(2):302-7.
Investigator’s Brochure, Edition 1.0, Feb 2020.
Kim BS, Howell MD, Sun K, et al. Treatment of Atopic Dermatitis With Ruxolitinib Cream
(JAK1/JAK2Inhibitor) or Triamcinolone Cream, Journal of Allergy and Clinical Immunology.
Published online: October 17, 2019.
Naegeli A, Flood E, Tucker J, et al. The Worst Itch Numeric Rating Scale for patients with
moderate to severe plaque psoriasis or psoriatic arthritis. Int J Dermatol. 2015 Jun;54(6):715-22.


Protocol ARQ-252-205
Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
Confidential
Page 69 of 72
Nakagawa H, Nemoto, Igarashi A, et al. Efficacy and safety of topical JTE-052, a Janus kinase
inhibitor, in Japanese adult patients with moderate-to severe atopic dermatitis: a phase II,
multicentre, randomized, vehicle-controlled clinical study. Br J Dermatology.
2018;178:424-432.
Ortiz PG, Hansen SH, Shah VP, et al. Impact of adult atopic dermatitis on topical drug
penetration: assessment by cutaneous microdialysis and tape stripping. Acta Derm Venereol.
2009;89:33-38.
O’Shea J, Gadina M. 2019. Selective Janus kinase inhibitors come of age. Nature Reviews
Rheumatology. 2019 Feb;15(2):74-75.
Ruzicka T, Lynde CW, Jemec GB, et al. Efficacy and safety of oral alitretinoin (9‐cis retinoic
acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of
a randomized, double‐blind, placebo‐controlled, multicentre trial. British Journal of
Dermatology. 2008;158(4):808‐17.
Villarino AV, Kanno Y, O'Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the
immune system. Nature Immunology. 2017;18:374-384.
Worm M, Bauer A, Elsner P, et al . Efficacy and safety of topical delgocitinib in patients with
chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study.
Br J Dermatol. 2019 Aug 29, doi: 10.1111/bjd.18469. [Epub ahead of print].


Protocol ARQ-252-205
Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
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Page 70 of 72
APPENDICES
Appendix 1.
Quality of Life in Hand Eczema Questionnaire (QOLHEQ)


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Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
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Page 71 of 72


Protocol ARQ-252-205
Arcutis Biotherapeutics, Inc.
Amendment 2
30 June 2020
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© DermIS 2003-2018

SAP_001.pdf: 
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Page 1 of 219
Statistical Analysis Plan
Sponsor:
Arcutis Biotherapeutics, Inc.
Protocol Title:
A Phase 1/2b, Multiple Dose and 12-Week, Parallel Group,
Double Blind, Dose Ranging, Vehicle-Controlled Study of the
Safety and Efficacy of ARQ-252 Cream 0.1% and ARQ-252
Cream 0.3% in Subjects with Chronic Hand Eczema
Protocol Number:
ARQ-252-205
Premier Research PCN:
ARCU211360
Document Version:
Final 1.0
Document Date:
09-Apr-2021


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Page 2 of 219
APPROVALS
Role
Signatures
Biostatistician
Print Name: Valerie H. Smith, MStat
Sign Name:
Peer Reviewer
Print Name: Patricia Rice, MS
Sign Name:
Arcutis
Biotherapeutics,
Inc. Representative
Print Name: David Berk, MD
Sign Name:
Arcutis
Biotherapeutics,
Inc. Representative
Print Name: Amy Feng, PhD
Sign Name:


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Page 3 of 219
DOCUMENT HISTORY
Not applicable.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Page 4 of 219
TABLE OF CONTENTS
1.
OVERVIEW ..................................................................................................................... 10
2.
STUDY OBJECTIVES AND ENDPOINTS.................................................................... 10
2.1.
Study Objectives......................................................................................................... 10
2.1.1. Primary Objectives...................................................................................................... 10
2.2.
Study Endpoints.......................................................................................................... 11
2.2.1. Efficacy Endpoints...................................................................................................... 11
2.2.2. Safety Endpoints......................................................................................................... 13
3.
OVERALL STUDY DESIGN AND PLAN..................................................................... 13
3.1.
Overall Design ............................................................................................................ 13
3.2.
Sample Size and Power............................................................................................... 14
3.3.
Study Population......................................................................................................... 14
3.4.
Treatments Administered............................................................................................ 14
3.5.
Method of Assigning Subjects to Treatment Groups.................................................. 15
3.6.
Blinding and Unblinding............................................................................................. 15
3.7.
Schedule of Events...................................................................................................... 16
4.
STATISTICAL ANALYSIS AND REPORTING ........................................................... 20
4.1.
Introduction................................................................................................................. 20
4.2.
Interim Analysis and Data Monitoring ....................................................................... 20
5.
ANALYSIS POPULATIONS .......................................................................................... 21
6.
GENERAL ISSUES FOR STATISTICAL ANALYSIS.................................................. 22
6.1.
Statistical Definitions and Algorithms........................................................................ 22
6.1.1. Baseline....................................................................................................................... 22
6.1.2. Adjustments for Covariates......................................................................................... 22
6.1.3. Multiple Comparisons................................................................................................. 22
6.1.4. Handling of Dropouts or Missing Data....................................................................... 23
6.1.5. Analysis Visit Windows ............................................................................................. 25
6.1.6. Pooling of Sites........................................................................................................... 27
6.1.7. Derived Variables ....................................................................................................... 27
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 30
6.1.9. Presentation of Cohorts and Treatments in Summaries.............................................. 31
7.
STUDY SUBJECTS AND DEMOGRAPHICS............................................................... 33
7.1.
Disposition of Subjects and Withdrawals................................................................... 33
7.2.
Protocol Violations and Deviations ............................................................................ 33
7.3.
Demographics and Other Baseline Characteristics..................................................... 33


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
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7.4.
Exposure and Compliance .......................................................................................... 34
8.
EFFICACY ANALYSIS .................................................................................................. 34
8.1.
Primary Efficacy Analysis.......................................................................................... 34
8.1.1. Investigator Global Assessment (IGA) Score of “Clear” or “Almost Clear” at
Week 12 ...................................................................................................................... 34
8.1.2. Sensitivity Analyses of the Primary Efficacy Endpoint ............................................. 36
8.2.
Secondary Efficacy Analysis...................................................................................... 37
8.2.1. Investigator Global Assessment (IGA)....................................................................... 37
8.2.2. Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score................................... 38
8.2.3. Hand Eczema Severity Index (HECSI)....................................................................... 39
8.2.4. Pain Numeric Rating Scale (NRS) Score.................................................................... 39
8.2.5. Quality of Life in Hand Eczema Questionnaire (QOLHEQ)...................................... 41
8.2.6. Percent Body Surface Area (BSA) Affected by Disease............................................ 41
8.3.
Exploratory Efficacy Analysis.................................................................................... 42
9.
SAFETY AND TOLERABILITY ANALYSIS............................................................... 42
9.1.
Adverse Events ........................................................................................................... 42
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 43
9.1.2. Deaths and Serious Adverse Events ........................................................................... 43
9.2.
Local Tolerability Assessments.................................................................................. 43
9.3.
Clinical Laboratory Evaluations ................................................................................. 43
9.4.
Vital Signs................................................................................................................... 44
9.5.
12-Lead Electrocardiograms....................................................................................... 44
9.6.
Physical Examination.................................................................................................. 44
9.7.
Concomitant Medications........................................................................................... 44
9.8.
Modified Total Lesion Symptom Score (mTLSS)...................................................... 44
10.
CHANGES FROM PLANNED ANALYSIS................................................................... 45
11.
OTHER PLANNED ANALYSIS..................................................................................... 46
11.1.
Pharmacokinetic Analysis........................................................................................... 46
12.
REFERENCES ................................................................................................................. 46
13.
TABLES, LISTINGS, AND FIGURES ........................................................................... 47
13.1.
Planned Table Descriptions ........................................................................................ 47
13.1.1. Demographic Data ...................................................................................................... 47
13.1.2. Efficacy Data .............................................................................................................. 48
13.1.3. Safety Data.................................................................................................................. 55
13.1.4. Pharmacokinetic Data................................................................................................. 58
13.2.
Planned Listing Descriptions...................................................................................... 58


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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14.
TABLES, LISTINGS, AND LISTING SHELLS............................................................. 60
14.1.
Standard Layout for all Tables, Listings, and Figures................................................ 60
14.2.
Planned Table Shells................................................................................................... 62
14.3.
Planned Listing Shells............................................................................................... 177


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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LIST OF TABLES
Table 1:
Cohort 1 (Phase 1) ..................................................................................................... 16
Table 2:
Cohort 2 (Phase 2b) .................................................................................................... 18
Table 3:
Analysis Visit Windows (Cohort 1 [Phase 1])............................................................ 25
Table 4:
Analysis Visit Windows (Cohort 2 [Phase 2b]).......................................................... 25
Table 5:
Analysis Visit Windows (Cohort 1 [Phase 1])............................................................ 26
Table 6:
Analysis Visit Windows (Cohort 2 [Phase 2b]).......................................................... 26
Table 7:
IGA ............................................................................................................................. 35
Table 8:
Demographic Data Summary Tables and Figures ...................................................... 47
Table 9:
Efficacy Data .............................................................................................................. 48
Table 10:
Safety Data................................................................................................................ 55
Table 11:
Pharmacokinetic Data............................................................................................... 58
Table 12:
Planned Listings........................................................................................................ 58
LIST OF FIGURES
Figure 1:
Standardized Layout ................................................................................................. 61


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Page 8 of 219
LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
ANCOVA
analysis of covariance
ASA
American Statistical Association
ATC
anatomical therapeutic chemical
BID
twice daily
BMI
body mass index
BSA
body surface area
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
COVID-19
novel coronavirus disease-19
CS
clinically significant
CSR
clinical study report
ECG
Electrocardiogram
eCRF
electronic case report form
EM
expectation-maximization
EMA
European Medicines Agency
FDA
Food and Drug Administration
HECSI
Hand Eczema Severity Index
ICH
International Conference on Harmonisation
IGA
investigator global assessment
IP
investigational product
IRT
interactive response technologies
ITT
intent-to-treat
LS
least-squares
MCMC
Markov-Chain Monte-Carlo
MedDRA
Medical Dictionary for Regulatory Activities
mTLSS
Modified Total Lesion Symptom Score


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Abbreviation
Definition
NA
not applicable
NCS
not clinically significant
ND
nail dystrophy
NRS
numeric rating scale
PK
Pharmacokinetics
PMM
predictive mean modeling
PP
per protocol
QD
once daily
QOLHEQ
Quality of Life in Hand Eczema Questionnaire
RSS
Royal Statistical Society
SAE
serious adverse event
SAF
Safety
SAP
statistical analysis plan
SAS®
a software system used for data analysis
SD
standard deviation
SE
standard error
SOC
system organ class
TEAE
treatment emergent adverse event
TLFs
tables, listings, and figures
WHO-DDE
World Health Organization Drug Dictionary Enhanced
WI-NRS
Worst Itch – Numeric Rating Scale


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
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Page 10 of 219
1.
OVERVIEW
This statistical analysis plan (SAP) describes the planned analysis and reporting for
Arcutis Biotherapeutics, Inc. protocol number ARQ-252-205 (A Phase 1/2b, Multiple Dose and
12-Week, Parallel Group, Double Blind, Dose Ranging, Vehicle-Controlled Study of the
Safety and Efficacy of ARQ-252 Cream 0.1% and ARQ-252 Cream 0.3% in Subjects with
Chronic Hand Eczema), dated 30-June-2020 Amendment Version 2. Reference materials for this
statistical plan include the protocol and the accompanying sample data collection documents.
Operational aspects related to collection and timing of planned clinical assessments are not
repeated in this SAP unless relevant to the planned analysis.
The structure and content of this SAP provides sufficient detail to meet the requirements
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA),
and International Conference on Harmonization (ICH) of Technical Requirements for
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical
Trials (ICH 1998). All work planned and reported for this SAP will follow internationally
accepted guidelines, published by the American Statistical Association (ASA 2018) and the
Royal Statistical Society (RSS 2014), for statistical practice.
The planned analyses identified in this SAP may be included in clinical study reports (CSRs),
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR.
The statistical plan described hereafter is an a priori plan. It will be submitted to file before any
unblinded inferential or descriptive analysis of data pertaining to Arcutis Biotherapeutics, Inc.’s
study ARQ-252-205. Any amendments to this plan that occur after unblinding for an interim
analysis will be performed by a study statistician who remains blinded to treatment codes and
outcomes.
2.
STUDY OBJECTIVES AND ENDPOINTS
2.1.
Study Objectives
2.1.1. Primary Objectives
The objectives of this study are as follows:
Phase 1 (Cohort 1):
•
To assess the safety, tolerability, and pharmacokinetics (PK) of once daily (QD)
application of ARQ-252 0.3% to both hands for 2 weeks in 6 subjects with chronic hand
eczema


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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Phase 2b (Cohort 2):
•
To assess the safety and efficacy of ARQ-252 cream 0.1% QD and ARQ-252 cream 0.3%
QD and twice daily (BID), vs vehicle applied QD and BID for 12 weeks to subjects with
chronic hand eczema
2.2.
Study Endpoints
2.2.1. Efficacy Endpoints
2.2.1.1.
Primary Efficacy Endpoint
Phase 1 (Cohort 1):
Not applicable.
Phase 2b (Cohort 2):
The primary endpoint of Cohort 2 is:
•
The rate of an Investigator Global Assessment (IGA) score of “clear” or “almost clear” at
Week 12
The primary estimand for the primary efficacy endpoint of this study is the odds of achieving
IGA score of “clear” or “almost clear” (i.e., IGA success) at 12 weeks; that is, the ratio of the
odds of achieving IGA success at 12 weeks ARQ-252 relative to the odds of success at 12 weeks
of using a matching vehicle cream. In the course of the 12-week randomized treatment period,
subjects may be exposed to possible known or unknown intercurrent events that could possibly
affect the estimand, such as treatment discontinuation due to a specific adverse effect or perhaps
a lack of effect. The “Treatment Policy Strategy” has been adopted for handling all known or
unknown intercurrent events in this study. To this end, the ITT principle will serve as the
analytical basis for interpreting the estimand. In other words, the odds ratio of achieving IGA
success for ARQ-252 relative to vehicle at 12 weeks will be evaluated regardless of the
occurrence of any such intercurrent event. This estimand shall be estimated using the
Cochran-Mantel-Haenszel (CMH) approach and applies to the following treatment comparisons:
•
ARQ-252 cream 0.3% BID versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.3% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.1% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream (all strengths and dose frequencies) versus vehicle cream (all dose
frequencies)
•
ARQ-252 cream 0.3% (all dose frequencies) versus vehicle cream (all dose frequencies)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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2.2.1.2.
Secondary Efficacy Endpoint(s)
Phase 1 (Cohort 1):
Not applicable.
Phase 2b (Cohort 2):
The secondary endpoints of Cohort 2 are:
•
The rate of achievement of IGA of “clear” or “almost clear” PLUS at least a 2-point
improvement from baseline at Weeks 2, 4, 8, 12, and 13
•
The rate of achievement of at least a 2-point improvement from baseline at Weeks 2, 4, 8,
12, and 13
•
Achievement of IGA of “clear” or “almost clear” at Weeks 2, 4, 8, and 13
•
Change in IGA score at Weeks 2, 4, 8, 12, and 13 as compared to baseline
•
Change and percent change in Worst Itch - Numeric Rating Scale (WI-NRS) pruritus
score at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 compared to baseline
•
The rate of achievement of ≥4-point reduction from baseline in WI-NRS pruritus score at
Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 in subjects with baseline WI-NRS
pruritus score of at least 4
•
Change and percent change in Hand Eczema Severity Index (HECSI) score at Weeks 2,
4, 8, 12, and 13 compared to baseline
•
Achievement of HECSI-75
•
Change and percent change in Pain Numeric Rating Scale (NRS) score from Baseline to
Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13
•
The rate of achievement of ≥4-point reduction from baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 4
•
The rate of achievement of ≥3-point reduction from baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 3
•
The rate of achievement of ≥2-point reduction from baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 2
•
Change and percent change from baseline in overall Quality of Life in Hand Eczema
Questionnaire (QOLHEQ) score at each study visit
•
Percent body surface area (BSA) affected by disease and % change from baseline in BSA
affected by disease at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 13 weeks.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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2.2.1.3.
Exploratory Efficacy Endpoint(s)
Phase 2b (Cohort 2):
The exploratory endpoint of Cohort 2 is:
•
Change from baseline in Nail Dystrophy at each visit.
2.2.2. Safety Endpoints
Phase 1 (Cohort 1):
The primary endpoint of Cohort 1 is safety, as measured by the incidence and severity of adverse
events (AEs), changes in laboratory parameters, tolerability, and PK.
Phase 2b (Cohort 2):
The safety endpoints for Phase 2b (Cohort 2) will be the same as for Phase 1 (Cohort 1), i.e., as
measured by the incidence and AEs, changes in laboratory parameters, tolerability, and PK.
3.
OVERALL STUDY DESIGN AND PLAN
3.1.
Overall Design
This is a phase 1/2b, multiple dose and 12-week, parallel group, double blind, dose ranging,
vehicle-controlled study of the safety and efficacy of ARQ-252 cream 0.1% and ARQ-252 cream
0.3% in subjects with chronic hand eczema.
There are 2 cohorts of subjects:
•
Cohort 1 is a multiple dose cohort in which subjects with chronic hand eczema will be
assigned to ARQ-252 cream 0.3% QD x 2 weeks to be applied to both hands.
Pharmacokinetics and tolerability will be evaluated.
•
Cohort 2 is a parallel group, double blind, vehicle-controlled cohort in which subjects
with chronic hand eczema will be randomized to ARQ-252 cream 0.3% QD, ARQ-252
cream 0.3% BID, ARQ-252 cream 0.1% QD, vehicle cream BID, or vehicle cream
QD x 12 weeks to be applied to both hands. Safety and efficacy will be evaluated.
A total of approximately 6 evaluable subjects will be enrolled in Cohort 1, and a total of
approximately 215 subjects will be enrolled in Cohort 2. After having met all inclusion criteria,
and none of the exclusion criteria, subjects in Cohort 1 will be assigned treatment with ARQ-252
cream 0.3% QD at the Baseline visit; and subjects in Cohort 2 will be randomized in a 2:2:1:1:1
ratio (ARQ-252 0.3% QD, ARQ-252 0.3% BID, ARQ-252 0.1% QD, vehicle cream QD, or
vehicle cream BID, respectively) and stratified by study site and IGA at baseline according to a
computer-generated randomization list.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 14 of 219
For subjects enrolled in Cohort 1, subject participation involves a minimum of 7 clinic visits
including Screening, Baseline/Day 1, Day 2, Day 8, Day 15, Day 16, and Day 22. Subjects will
be treated with investigational product (ARQ-252 cream 0.3% QD) for 2 weeks. The interval
between the Screening and Baseline visits could be up to 4 weeks, therefore the anticipated
maximum duration of subject participation is 7 weeks.
For subjects enrolled in Cohort 2, subject participation involves a minimum of 7 clinic visits
including Screening, Baseline/Day 1, Week 2, Week 4, Week 8, Week 12, and Week 13.
Subjects will be randomized to a treatment group and will be treated with investigational product
for 12 weeks. The interval between the Screening and Baseline visits could be up to 4 weeks,
therefore the anticipated maximum duration of subject participation is 17 weeks.
3.2.
Sample Size and Power
Cohort 1 will include approximately 6 evaluable subjects, which is deemed adequate for the
purpose of evaluating safety and PK before Cohort 2 commences.
There are approximately 215 subjects planned for Cohort 2. The primary statistical comparisons
will be to assess the ARQ-252 cream 0.3% BID group versus the vehicle BID group, to assess
the ARQ-252 cream 0.3% QD group versus the vehicle QD group, and to assess the ARQ-252
cream 0.1% QD group versus the vehicle QD group. A sample size of 55 per active arm and
28 per vehicle arm will provide approximately 85% power at the 2-sided 10% significance level
to detect a difference in the rate of subjects attaining an IGA score of clear or almost clear
(for each ARQ-252-treated group versus vehicle group within the same daily dosing frequency),
assuming an active treatment response rate of 45% and a vehicle response rate of 15%. For
testing each active arm of 55 subjects versus the combined vehicle arms of 56 subjects, this
sample size provides over 90% power for the comparison of the rate of subjects attaining an IGA
score of clear or almost clear. This is based on a 2-group X2 test of equal proportions (without
continuity correction).
3.3.
Study Population
Subjects will be adults (≥18 years of age) males or females with chronic hand eczema involving
at least 0.3% BSA, with a minimum IGA of at least “Mild” (2) at baseline.
3.4.
Treatments Administered
Cohort 1 will include approximately 6 evaluable subjects; all subjects are to receive ARQ-252
cream 0.3% QD.
Approximately 61 subjects will receive ARQ-252 cream 0.3% QD, approximately 61 subjects
will receive ARQ-252 cream 0.3% BID, approximately 31 subjects will receive ARQ-252 cream
0.1% QD, approximately 31 subjects will receive matching vehicle cream QD, and
approximately 31 subjects will receive vehicle cream BID. The randomization scheme will be
2:2:1:1:1 between these 5 treatment groups, stratified by study site and IGA at Baseline.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 15 of 219
3.5.
Method of Assigning Subjects to Treatment Groups
Phase 1 (Cohort 1)
Phase 1 (Cohort 1) is open label and all enrolled subjects will be assigned treatment with
ARQ‑252 cream 0.3% QD at the Baseline visit. Subjects will be enrolled at the Baseline visit
after the Investigator confirms that the subject meets all eligibility criteria listed in the protocol.
Enrollment will be documented by the completion of the Enrollment Notification Form.
Phase 2b (Cohort 2)
Phase 2b (Cohort 2) is randomized. Randomization will take place at the Baseline visit after the
Investigator confirms that the subject meets all eligibility criteria listed in the protocol. Subjects
will be randomly assigned to apply ARQ-252 0.3% QD, ARQ-252 0.3% BID, ARQ-252
0.1% QD, vehicle cream QD, or vehicle cream BID by an interactive response technology
system (IRT).
Assignment of treatment arm will be made at a 2:2:1:1:1 ratio and stratified by study site and
IGA at baseline according to a computer-generated randomization list. Kits containing tubes of
investigational product will be assigned to each subject by the IRT system. A subject may
receive more than one kit for the treatment period. The kits and tubes will be labeled with a
unique number, in a blinded manner.
3.6.
Blinding and Unblinding
Phase 1 (Cohort 1) is not blinded.
Phase 2b (Cohort 2) is double-blinded, therefore neither the subjects nor the Investigator and
clinical personnel will be aware of which investigational product (ARQ-252 0.1% cream,
ARQ‑252 0.3% cream, or vehicle cream) an individual subject receives. The subjects,
Investigator, and clinical personnel will be aware of whether study is to be applied once daily or
twice daily.
In the event of a medical emergency where breaking the blind is required to provide medical care
to the subject, the Investigator may obtain the treatment assignment directly from the IRT system
for that subject. Refer to the current version of the IRT plan for details on unblinding. Treatment
assignments should, however, remain blinded unless assignment knowledge is necessary to
determine subject emergency medical care. The rationale for unblinding must be clearly
explained in source documentation and on the CRF, along with the date on which the treatment
assignment was obtained. The Investigator is requested to contact the Sponsor promptly in the
event of any treatment unblinding.
Blinding of study treatment is critical to the integrity of this clinical trial and therefore, if a
subject’s treatment assignment is disclosed to the Investigator, the subject will have the study
treatment discontinued. All subjects will be followed until study completion unless consent to do
so is specifically withdrawn by the subject.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 16 of 219
3.7.
Schedule of Events
The schedule of events for Cohort 1 (Phase 1) is presented in Table 1, and the schedule of events
for Cohort 2 (Phase 2a) is presented in Table 2.
Table 1:
Cohort 1 (Phase 1)
Study Procedure
Screening
Baseline
Day 1
PK
Collection
Day 2
Day 8
Week 2
Day 15
PK
Collection
Day 16
Week 3
Day 22
Visit
1
2
3
4
5
6
7
Visit Window
-4 Weeks
+/- 2 hrs
+/-1 day
+/- 1 day
+/- 2 hrs
+/- 3 days
Informed Consent
X
Demographics
X
Medical and Surgical History
X
Physical examinationa
X
X
X
X
X
I/E criteria
X
X
Hematology, Serum
Chemistries, Urine Analysis,
TSH, T4b
X
X
X
X
X
Vital signs, weight, heightc
X
X
X
X
X
Local tolerability assessmentd
X
X
X
BSA, IGA, HECSIe
X
X
X
WI-NRS, NRS Painf
X
Completed daily from Day 1-Day 15
Urine pregnancy testg
X
X
X
X
Serum pregnancy testg
X
Follicle-Stimulating Hormone
(FSH)h
X
Resting 12-lead ECG
X
X
PK samplingi
X
X
X
X
X
IP application in clinicj
X
X
X
Dispense IP
X
Weigh investigational product
containerk
X
X
Dispense/review diary
X
X
X
Adverse event assessmentl
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 17 of 219
Footnotes from table above:
a
Limited physical examination: skin, lungs, and heart only.
b
All samples listed to be collected at Visits 1, 2, 4, 5, and 7. If Baseline visit occurs within 14 days of Screening,
the Screening lab results may be utilized.
c
Height to be measured only at Visit 2 (Day 1). Weight will be collected at Baseline, Visits 4, 5 and 7.
d
Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of skin
irritation (Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s ‘0-3’
burning/stinging assessment. Note for investigator tolerability assessments: reactions at the site of IP
application, which may occur post-Baseline, should be differentiated from the preexisting inflammation
associated with the subject’s chronic hand eczema.
e
BSA will be measured as the affected BSA for each side of each hand. Affected areas of the lateral aspects of the
fingers and hands should be assigned to the palmar surface. IGA will be a 5-point scale ranging from clear
(0) to severe (4). IGA should be completed prior to other physician assessments and by the same Evaluator
at each study visit. HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand
eczema and the extent of the lesions on each of 5 distinct hand anatomic areas by use of standard scales. The total
HECSI score is based on a 4-point clinical sign severity scale ranging from 0 (none/absent) to 3 (severe) and a
5-point scale rating the different affected hand anatomic area(s) ranging from 0 (0% affected area) to 4
(76% to 100% affected area).
f
Subjects will complete the WI-NRS pruritus assessment and NRS Pain assessment in the clinic during screening
and then daily at home from the Baseline/Day 1 visit through the Day 15 visit.
g
A serum pregnancy test will be administered to all females of child-bearing potential at Screening. A urine
pregnancy test will be administered at Visits 2, 4, 5, and 7 to all females of childbearing potential. A negative
result is required for continued participation in the study, and results must be available prior to dispensing of
investigational product.
h
FSH will be performed (if indicated) at Screening to confirm post-menopausal status.
i
On the first day of dosing (Day 1), PK samples will be collected at 1, 2, 4, 6 (all +/- 10 mins) and 24 hours
post-dose administration (Day 2, +/- 2 hours). On Day 15 (last dose application), PK samples will be collected
pre-dose, 1, 2, 4, 6, (all +/- 10 mins) and 24 hours post dose administration (Day 16, +/- 2 hours). For 24-hour
time points, subjects return to the clinic on the following day within 2 hours of the IP application time from the
previous day for pre-dose PK plasma sample. A pre-dose PK sample will be taken at Day 8.
j
Clinic personnel will apply assigned IP on Visits 2, 4 and 5 (Baseline, Day 8 and Day 15). Every tube should be
weighed before and after IP application and weights recorded. For the 24-hour PK sampling time point the
application of investigational product should occur after the PK sample has been collected.
k
Subject should return with investigational product kit at each Visit. Every tube should be weighed before and after
use and weights recorded when dispensed and returned.
l
Any emergent AEs will be followed in the clinic for up to 1 month at the Investigator’s discretion until resolved or
otherwise judged as clinically stable


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 18 of 219
Table 2:
Cohort 2 (Phase 2b)
Study Procedure
Screen
Baseline
Day 1
Wk 2
Day 15
Wk 4
Day 29
Wk 8
Day 57
Wk 12
Day 85
Wk 13
Day 92
Visit
1
2
3
4
5
6
7
Visit Window
-4 weeks
+/- 3 days
+/- 5 days
+/- 5 days
+/- 7 days
+/- 3 days
Informed consent
X
Demographics
X
Medical and surgical history
X
Physical examinationa
X
X
X
Vital signs, height, weightb
X
X
X
X
X
X
X
I/E criteria
X
X
Randomization
X
Hematology, Serum
Chemistries, UA, TSH/T4c
X
X
X
X
X
Resting 12-lead ECG
X
X
X
BSA, IGA, HECSId
X
X
X
X
X
X
X
NRS pain, WI-NRSe
X
Completed daily from Day 1 to Week 13 Visit
QOLHEQe
X
X
X
X
X
X
X
Nail dystrophy assessmentf
X
X
X
X
X
X
Local Tolerability
Assessmentsg
X
X
X
X
X
Optional Photographyh
X
X
X
X
X
X
Urine pregnancy testi
X
X
X
X
X
Serum pregnancy testi
X
Follicle-Stimulating
Hormone (FSH)j
X
PK samplingk
X
X
X
IP application/Subject
training in clinicl
X
X
X
X
X
Dispense IP kitm
X
X
X
X
X
Dispense/review diary
X
X
X
X
X
Weigh IP tubesn
X
X
X
X
X
Compliance calculationo
X
X
X
X
X
Adverse event assessmentp
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 19 of 219
Footnotes from table above:
a Limited physical examination: skin, lungs, and heart only
b Height will be collected at Visit 2 (Baseline/Day 1) only. Weight will be collected at Baseline, Weeks 4, 8 and 12.
c If Baseline visit occurs within 14 days of Screening, the Screening lab results may be utilized.
d BSA will be measured as the affected BSA for each side of each hand. Affected areas of the lateral aspects of the
fingers and hands should be assigned to the palmar surface. IGA will be a 5-point scale ranging from clear
(0) to severe (4). IGA should be completed prior to other physician assessments and by the same Evaluator
at each study visit. HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand
eczema and the extent of the lesions on each of 5 distinct hand anatomic areas by use of standard scales. The total
HECSI score is based on a 4-point clinical sign severity scale ranging from 0 (none/absent) to 3 (severe) and a
5-point scale rating the different affected hand anatomic area(s) ranging from 0 (0% affected area) to 4
(76% to 100% affected area).
e Subjects will complete the WI-NRS pruritus assessment and NRS Pain assessment in the clinic during Screening
and then daily at home from the Baseline/Day 1 visit until the Week 13 visit. QOLHEQ = Quality of Life in Hand
Eczema Questionnaire will be completed at each visit.
f Assessment of nail dystrophy including Baseline identification of the nail with the worst dystrophy and
measurement of the millimeters of normal appearing nail distal to the cuticle post Baseline. Sites participating in
optional photography will obtain photos of nail with the worst dystrophy at Baseline/Day 1 and at subsequent
visits.
g Local tolerability assessments to be recorded prior to IP application for the Investigator assessment of skin
irritation (Berger and Bowman skin irritation score) and 10-15 minutes post IP application for the subject’s ‘0-3’
burning/stinging assessment. Note for investigator tolerability assessments: reactions at the site of IP
application, which may occur post-Baseline, should be differentiated from the preexisting inflammation
associated with the subject’s chronic hand eczema.
h Photography will be performed at selected investigational sites. Photography will be optional. All efforts will be
made to de-identify the subjects. Sites participating in optional photography will obtain photos of nail with the
worst dystrophy at Baseline/Day 1 and at subsequent visits.
i A serum pregnancy test will be administered to all females of childbearing potential at Screening. A urine
pregnancy test will be administered at Baseline, Weeks 4, 8, 12 and 13. A negative result is required for continued
participation in the study, and results must be available prior to dispensing of investigational product.
j FSH will be performed (if indicated) at Screening to confirm post-menopausal status.
k PK assessments will be collected from all subjects at Days 1, 29 and 85. The draws will be pre-dose IP application
in the clinic.
l Subjects to apply assigned IP in clinic at these visits. The time of application will be documented.
m Kits will be dispensed at Baseline, Weeks 2, 4 and 8. Dispensing at Week 12 requires approval from the
Medical Monitor. See IP Handling Manual for details.
n Each IP tube will be weighed prior to dispensing at the Baseline visit and at each follow-up clinic visit according
to the Schedule of Visits and Assessments. When IP is applied in the clinic, the IP tube will be weighed before
and after IP application. See IP Handling Manual for details.
o Compliance calculation is described in the IP Handling Manual.
p Any emergent AEs will be followed in the clinic for up to one month at the Investigator’s discretion until resolved
or otherwise judged as clinically stable.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 20 of 219
4.
STATISTICAL ANALYSIS AND REPORTING
4.1.
Introduction
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and
graphical representations will primarily use SAS (release 9.4 or higher). If the use of other
software is warranted, the final statistical methodology report will detail what software was used
for what purposes.
Continuous (quantitative) variable summaries will include the number of subjects (n) with
non-missing values, mean, standard deviation (SD), median, minimum, and maximum.
Categorical (qualitative) variable summaries will include the frequency and percentage of
subjects who are in the particular category or each possible value. In general, the denominator
for the percentage calculation will be based upon the total number of subjects in the study
population for each treatment group, unless otherwise specified.
The minimum and maximum will be reported with the same degree of precision (i.e., the same
number of decimal places) as the observed data. Measures of location (mean and median) will be
reported to 1 degree of precision more than the observed data and measures of spread
(SD, standard error [SE]) will be reported to 2 degrees of precision more than the observed data.
Percentages will be presented to 1 decimal place, unless otherwise specified.
Unless otherwise indicated, all statistical tests will be conducted at the 0.1 significance level
using 2-tailed tests, and P values will be reported. For the purposes of statistical comparisons, the
vehicle BID and vehicle QD groups will be pooled together. Testing will be performed for:
•
ARQ-252 cream 0.3% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.3% BID versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.1% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream (all strengths and dose frequencies) versus vehicle cream (all dose
frequencies)
•
ARQ-252 cream 0.3% (all dose frequencies) versus vehicle cream (all dose frequencies)
Corresponding 90% and 95% confidence intervals (CIs) will be presented for statistical tests.
Testing will be performed for the primary endpoint of IGA clear or almost clear, for change from
baseline in the HECSI score, and for the percent change from baseline in the HECSI score;
however, P values will be provided for informational purposes for other endpoints as specified in
Section 8. The primary statistical comparisons and evaluations of secondary endpoints will not
be adjusted for multiplicity.
4.2.
Interim Analysis and Data Monitoring
No interim efficacy analyses are planned.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 21 of 219
5.
ANALYSIS POPULATIONS
The following analysis populations are planned for this study:
•
Safety Population (SAF): The Safety population will include all subjects who are
enrolled (Cohort 1) or randomized (Cohort 2) and received at least 1 confirmed dose of
investigational product (IP). This population will be used for all safety analyses and will
be defined separately for each cohort.
•
All Treated Population (ALLTRT): The All Treated population will include all
subjects in the Safety population in Cohort 1. This population will be the primary
analysis population for the analysis of Cohort 1 efficacy endpoints.
•
Intent-To-Treat Population (ITT): The ITT population will include all subjects
randomized to Cohort 2. This population will be the primary analysis population for the
analysis of Cohort 2 efficacy endpoints.
•
Per Protocol Population (PP): The PP population will include all subjects in the Safety
population in Cohort 2, who were at least 80% compliant with study medication
application, and showed no important deviations from the study protocol that would
affect the interpretation of efficacy. This population will be used as a sensitivity analysis
of Cohort 2 primary and select secondary efficacy endpoints (i.e., IGA, WI-NRS, and
HECSI analyses).
•
Pruritus Population (PRU4): The PRU4 population is a subset of the All Treated
population (Cohort 1) and ITT population (Cohort 2) and includes subjects with WI-NRS
score ≥4 at baseline. This population will be used for the analysis of achievement of a
4-point reduction in WI-NRS score as compared to baseline for this subset of subjects.
•
Pain NRS Population (PNRS4): The PNRS4 population is a subset of the All Treated
population (Cohort 1) and ITT population (Cohort 2) and includes subjects with Pain
NRS score ≥4 at baseline. This population will be used for the analysis of achievement of
a 4-point reduction in Pain NRS score as compared to baseline for this subset of subjects.
•
Pain NRS Population (PNRS3): The PNRS3 population is a subset of the All Treated
population (Cohort 1) and ITT population (Cohort 2) and includes subjects with Pain
NRS score ≥3 at baseline. This population will be used for the analysis of achievement of
a 3-point reduction in Pain NRS score as compared to baseline for this subset of subjects.
•
Pain NRS Population (PNRS2): The PNRS2 population is a subset of the All Treated
population (Cohort 1) and ITT population (Cohort 2) and includes subjects with Pain
NRS score ≥2 at baseline. This population will be used for the analysis of achievement of
a 2-point reduction in Pain NRS score as compared to baseline for this subset of subjects.
•
Nail Dystrophy Population (ND): The ND population is a subset of the ITT population
and includes subjects with nail dystrophy at baseline. This population will be used for the
analysis of nail dystrophy for this subset of subjects.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 22 of 219
•
Pharmacokinetic Population (PK): The PK population will include all subjects
receiving the active drug with sufficient plasma concentrations of ARQ-252 to define a
profile, as determined by the pharmacokineticist. This population will be used for
analyses of PK parameters.
Assignment of subjects to populations will be confirmed at a blinded data review meeting to be
held before the study database is locked.
6.
GENERAL ISSUES FOR STATISTICAL ANALYSIS
6.1.
Statistical Definitions and Algorithms
6.1.1. Baseline
For assessments where time was recorded (e.g., ECG), the last observation recorded before the
first application of study drug will be used as the baseline observation for all calculations of
change from baseline. For assessments where time was not recorded (excluding WI-NRS and
Pain NRS), the last observation recorded on or before the day of first application of study drug
will be used as the baseline observation for all calculations of change from baseline. For
WI-NRS and Pain NRS, since diaries were completed daily at home from the Baseline/Day 1
visit until end of treatment, baseline is defined as the last observation recorded before the day of
first application of study drug.
For assessments that are collected both before and after application of study drug at the
Baseline/Day 1 visit, the last observation recorded before the first dose of study will be used as
the baseline observation. For assessments collected only after application of study drug, no
baseline will be defined (except for subject local tolerability; in this case, baseline is defined as
the first non-missing observation recorded after the first application of study drug). If the
tolerability assessments are not done as per protocol Section 5.1.7, those records will be
excluded from the analysis.
6.1.2. Adjustments for Covariates
Covariates for this study include pooled site group (see Section 6.1.6) and IGA severity at
baseline (mild, moderate, or severe). Subgroup analyses may be generated for the baseline
covariates.
6.1.3. Multiple Comparisons
No adjustments for multiple comparisons will be made for this study.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 23 of 219
6.1.4. Handling of Dropouts or Missing Data
Any subject who prematurely withdraws from the study will have their last available data
assigned to an analysis window as described in Section 6.1.5.
For the primary efficacy endpoint of IGA score (Phase 2b/Cohort 2 only), the primary analysis
will impute missing values using a regression-based multiple imputation model. This is a three
step process.
1. The first step is to understand the pattern of missingness. In order to perform the multiple
imputation, a monotone missing pattern has to be achieved. For example, if there exist
values for baseline, Week 8, and Week 12 visits, but missing values for the Week 2 or
4 visits, the Markov-Chain Monte-Carlo (MCMC) method will be used to impute the
small amount of missing data that may be missing at the intermediate visits that is
required to make the missing data pattern monotone before applying the multiple
imputation algorithm. This method uses a non-informative Jeffreys prior to derive the
posterior mode from the expectation-maximization (EM) algorithm as the starting values
for the MCMC method. MCMC method will use seed of 74746759. The IGA score will
be treated as a continuous variable for this step. To avoid values that could not be
observed in practice, imputed values will be constrained to be integers in the range of
0 to 4.
a.
The table below will determine the number of datasets to be imputed in this step.
Determine the proportion of datapoints with non-monotone pattern across all
visits and subjects which could be derived as a percentage of number of
nonmonotone data points/total number of expected data points.
This can be determined as

∗100
Non-monotone Missing Data
Number of Imputed Datasets
≤2%
1
> 2% to ≤5%
3
> 5%
10
2. Once the monotone pattern is achieved, the next step is to implement the imputation
algorithm. For this, the Predictive Mean Matching method (PMM) will be used. This
method is particularly helpful if the normality assumption is violated. For subjects with
complete data up to a particular visit, a PMM model will be fit that includes the outcome
at that visit as the dependent variable and as independent variables, IGA score outcomes
at previous visits, treatment group, and pooled site group using a seed of 88734121. This
process will be repeated 25 times, resulting in a total of 25 to 250 complete analysis


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 24 of 219
datasets, depending on the number of imputed monotone datasets that are required. The
seed or number of imputed datasets may be changed after unblinding in case of any issues
with the imputation process, and it will be documented in the CSR if any change is
required.
3. For each completed dataset, compute the necessary derived variables. The dichotomous
success rate (clear or almost clear) will be derived. The results obtained will be analyzed
using the CMH analysis for each of the complete analysis data sets stratified by baseline
IGA score and site. The results will be combined into one multiple imputation inference
(odds ratio, associated CI, and P value) using PROC MIANALYZE as illustrated below
(Ratitch 2013).
This approach to imputation should be superior to other strategies such as carrying forward the
last available observation, which may yield unrealistic imputed values. Also, the use of multiple
imputation avoids the problem of artificially increasing power through data imputation
associated with single-imputation methods because it accounts for the uncertainty associated
with the imputation. Other missing data will not be imputed, with the exception of incomplete
dates as described in Section 6.1.8. For responder analyses, missing data will be treated as a
nonresponse with the exception of IGA. Only observed data will be summarized using
descriptive statistics.
The SAS pseudo code for the multiple imputation process is listed below:
Step 1:
proc mi data=example seed=74746759 nimpute=XX round=1 out=example_1;
mcmc impute=monotone;
var <baseline score> ………… <visit12 score>;
run;
Step 2:
proc mi data=example_1 seed=88734121 nimpute=XX
out=example_2;
class <treatment> <site>;
monotone regpmm(<baseline score> ………… <visit12 score>);
var <treatment> <site> <baseline score> ………… <visit12 score>;
run;
XX will be the determined based on the proportion of missing data across visits.
Step 3: This step involves running CMH test stratified by baseline IGA score and site on each
completed dataset and combining the results using PROC MIANALYZE.
proc freq data=example noprint;
by <imputationnumber> <visit> ;
tables <site> * <BL IGA> * <treatment> * <outcome> / cmh alpha=0.1;
output out=example_stat cmh;
run;


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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In order to apply PROC MIANALYZE, normalizing transformations have to be applied to odds
ratio. P values are obtained using Wilson Hilferty transformation as illustrated
(Ratitch 2013).
6.1.5. Analysis Visit Windows
6.1.5.1.
Non-Diary Assessments
Visits will be analyzed as scheduled (i.e., not subject to visit windowing). Unscheduled, early
termination, and/or repeated measurements will only be included if a scheduled measurement is
not available and the unscheduled, early termination, or repeated measurement falls within the
analysis visit windows as described in Table 3 (Cohort 1 [Phase 1]) and Table 4
(Cohort 2 [Phase 2b]). The windows follow the Schedule of Events in Table 1 and Table 2.
Visits falling outside of these windows will not be windowed (e.g., an unscheduled visit before
first application of study drug). Unscheduled/repeated measurements will be listed.
Table 3:
Analysis Visit Windows (Cohort 1 [Phase 1])
Visit
Name
Analysis Visit
Number
Target Start
Day
Lower
Limit
Upper
Limit
Week 1
2
8
2
11
Week 2
3
15
12
18
Week 3
4
22
19
--
Table 4:
Analysis Visit Windows (Cohort 2 [Phase 2b])
Visit
Name
Analysis Visit
Number
Target Start
Day
Lower
Limit
Upper
Limit
Week 2
3
14
2
22
Week 4
5
28
23
42
Week 8
6
56
43
70
Week 12
7
85
71
90
Week 13
8
92
91
--
6.1.5.2.
Diary Assessments (WI-NRS, Pain NRS)
Diary entries will be assigned to a study week for analysis based on the study day relative to the
first application of study drug according to Table 5 (Cohort 1 [Phase 1]) and Table 6
(Cohort 2 [Phase 2]).


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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Table 5:
Analysis Visit Windows (Cohort 1 [Phase 1])
Visit
Name
Analysis Visit
Number
Lower
Limit
Upper
Limit
Study Week 1
101
1
7
Study Week 2
102
8
14 #
# Data may have been collected for subjects past Day 14; any Diary entries recorded after this day will not be
presented in any summaries. However, all Diary entries will be presented in the data listings; entries after
Day 14 will be presented as Week >2.
Table 6:
Analysis Visit Windows (Cohort 2 [Phase 2b])
Visit
Name
Analysis Visit
Number
Lower
Limit
Upper
Limit
Study Week 1
101
1
7
Study Week 2
102
8
14
Study Week 3
103
15
21
Study Week 4
104
22
28
Study Week 5
105
29
35
Study Week 6
106
36
42
Study Week 7
107
43
49
Study Week 8
108
50
56
Study Week 9
109
57
63
Study Week 10
110
64
70
Study Week 11
111
71
77
Study Week 12
112
78
84
Study Week 13
113
85
91 #
# Data may have been collected for subjects past Day 91; any Diary entries recorded after this day will not be
presented in any summaries. However, all Diary entries will be presented in the data listings; entries after Day
91 will be presented as Week >13.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 27 of 219
6.1.6. Pooling of Sites
Sites will be pooled for statistical analysis as follows. For analysis, sites should have a minimum
of 10 randomized subjects. The smallest sites will be grouped sequentially in order of smallest to
largest within each country, restricting to those sites that did not meet the minimum enrollment
of 10, until each pooled site has a minimum of 10 subjects within each country with at least
1 subject in each treatment group.
6.1.7. Derived Variables
•
Study Week = 7-day periods starting on Day 1, as described in Section 6.1.5.2. For
example, Study Week 1 corresponds to Days 1 to 7. This is in contrast to Study Visit,
which describes the actual clinic visit week. The nomenclature of “Study Week” will be
used with respect Pain NRS and WI-NRS analyses; otherwise, “Study Visit” will be used.
•
IGA Improvement = achievement of at least a 2-point improvement (i.e., reduction) in
IGA score from baseline.
•
IGA Success = post-baseline IGA of “Clear” or “Almost Clear” PLUS achievement of at
least a 2-point improvement (i.e., reduction) in IGA score from baseline.
•
Average Weekly WI-NRS Pruritus Score = WI-NRS pruritus scores will be assigned to
a particular study week based on the study week window, as shown in Section 6.1.5.2. If
2 or more observations are present for a single day, those observations will be averaged
into a single daily value before calculating the average weekly score. The average of the
reported (non-missing) WI-NRS pruritus scores assigned to each study week will be
calculated. If at least 1 WI-NRS pruritus score is present in this time period, the average
weekly WI-NRS pruritus score will be calculated; otherwise the average weekly score
will be missing for that week.
•
WI-NRS 4-point Reduction = achievement of a 4-point reduction in WI-NRS pruritus
score at each study week compared to baseline, calculated only for subjects with a
WI-NRS pruritus score of ≥4 at baseline (PRU4 population).
•
HECSI Fingertips Subscore = (E + I + V + F + S + O) * Ex,
where E, I, V, F, S, and O, are erythema, infiltration/papulation, vesicles, fissures, scale,
and oedema, respectively, scored on a scale of 0 to 3 (none to severe); Ex is estimated
area of skin involved, graded on a scale of 0 to 4. The range for the HECSI Fingertips
subscore is 0 to 72. If any of the component scores are missing, the HECSI Fingertips
subscore cannot be calculated; however, if the estimated area of skin involved = 0, the
HECSI Fingertips subscore will be set to 0. Lower scores indicate better outcomes.
•
HECSI Fingers (except tips) Subscore = (E + I + V + F + S + O) * Ex,
where E, I, V, F, S, and O, are erythema, infiltration/papulation, vesicles, fissures, scale,
and oedema, respectively, scored on a scale of 0 to 3 (none to severe); Ex is estimated
area of skin involved, graded on a scale of 0 to 4. The range for the HECSI Fingers
(except tips) subscore is 0 to 72. If any of the component scores are missing, the HECSI
Fingers (except tips) subscore cannot be calculated; however, if the estimated area of skin


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
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involved = 0, the HECSI Fingers (except tips) subscore will be set to 0. Lower scores
indicate better outcomes.
•
HECSI Palm of Hands Subscore = (E + I + V + F + S + O) * Ex,
where E, I, V, F, S, and O, are erythema, infiltration/papulation, vesicles, fissures, scale,
and oedema, respectively, scored on a scale of 0 to 3 (none to severe); Ex is estimated
area of skin involved, graded on a scale of 0 to 4. The range for the HECSI Palm of
Hands subscore is 0 to 72. If any of the component scores are missing, the HECSI Palm
of Hands subscore cannot be calculated; however, if the estimated area of skin
involved = 0, the HECSI Palm of Hands subscore will be set to 0. Lower scores indicate
better outcomes.
•
HECSI Back of Hands Subscore = (E + I + V + F + S + O) * Ex,
where E, I, V, F, S, and O, are erythema, infiltration/papulation, vesicles, fissures, scale,
and oedema, respectively, scored on a scale of 0 to 3 (none to severe); Ex is estimated
area of skin involved, graded on a scale of 0 to 4. The range for the HECSI Back of
Hands subscore is 0 to 72. If any of the component scores are missing, the HECSI
Back of Hands subscore cannot be calculated; however, if the estimated area of skin
involved = 0, the HECSI Back of Hands subscore will be set to 0. Lower scores indicate
better outcomes.
•
HECSI Wrists Subscore = (E + I + V + F + S + O) * Ex,
where E, I, V, F, S, and O, are erythema, infiltration/papulation, vesicles, fissures, scale,
and oedema, respectively, scored on a scale of 0 to 3 (none to severe); Ex is estimated
area of skin involved, graded on a scale of 0 to 4. The range for the HECSI Wrists
subscore is 0 to 72. If any of the component scores are missing, the HECSI Wrists
subscore cannot be calculated; however, if the estimated area of skin involved = 0, the
HECSI Wrists subscore will be set to 0. Lower scores indicate better outcomes.
•
HECSI Total Score = sum of HECSI Fingertips, Fingers (except tips), Palm of Hands,
Back of Hands, and Wrists subscores. The range for the HECSI Total score is 0 to 360.
Lower scores indicate better outcomes.
•
HECSI-75 = achievement of a 75% reduction in HECSI total score from baseline.
•
Average Weekly Pain NRS Score = Pain NRS scores will be assigned to a particular
study week based on the study week window, as shown in Section 6.1.5.2. If 2 or more
observations are present for a single day, those observations will be averaged into a
single daily value before calculating the average weekly score. The average of the
reported (non-missing) Pain NRS scores assigned to each study week will be calculated.
If at least 1 Pain NRS score is present in this time period, the average weekly Pain NRS
score will be calculated; otherwise the average weekly score will be missing for that
week.
•
Pain NRS 4-point Reduction = achievement of a 4-point reduction in Pain NRS score at
each study week compared to baseline, calculated only for subjects with a Pain NRS
score of ≥4 at baseline (PNRS4 population).


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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•
QOLHEQ Symptoms Subscore = sum of QOLHEQ questions 1, 6, 9, 11, 20, 23, and
28. Questions 1, 6, 9, 11, 20, and 23 are scored such that never = 0, rarely = 1, sometimes
= 2, often = 3, and all the time = 4; question 28 is scored such that never = 0, rarely = 1,
sometimes = 1, often = 2, and all the time = 3. The range for QOLHEQ Symptoms
subscore is 0 to 27, where lower scores indicate better outcomes. If 1 question has a
missing result, set the missing result to 0 before summing; if more than 1 question is
missing, then the QOLHEQ Symptoms subscore cannot be calculated.
•
QOLHEQ Emotions Subscore = sum of QOLHEQ questions 5, 8, 10, 16, 19, 21, 27,
and 30. Questions 5, 8, 16, 19, 21, 27, and 30 are scored such that never = 0, rarely = 1,
sometimes = 2, often = 3, and all the time = 4; question 10 is scored such that never = 0,
rarely = 1, sometimes = 1, often = 2, and all the time = 3. The range for QOLHEQ
Emotions subscore is 0 to 31, where lower scores indicate better outcomes. If 1 question
has a missing result, set the missing result to 0 before summing; if more than 1 question
is missing, then the QOLHEQ Emotions subscore cannot be calculated.
•
QOLHEQ Limitations in Functioning Subscore = sum of QOLHEQ questions 2, 3, 12,
14, 15, 17, 25, and 29. All questions are scored such that never = 0, rarely = 1, sometimes
= 2, often = 3, and all the time = 4. The range for QOLHEQ Limitations in Functioning
subscore is 0 to 32, where lower scores indicate better outcomes. If 1 question has a
missing result, set the missing result to 0 before summing; if more than 1 question is
missing, then the QOLHEQ Limitations in Functioning subscore cannot be calculated.
•
QOLHEQ Treatment and Prevention Subscore = sum of QOLHEQ questions 4, 7, 13,
18, 22, 24, and 26. Questions 7, 13, 18, 22, 24, and 26 are scored such that never = 0,
rarely = 1, sometimes = 2, often = 3, and all the time = 4; question 4 is scored such that
never = 0, rarely = 1, sometimes = 1, often = 2, and all the time = 3. The range for
QOLHEQ Treatment and Prevention subscore is 0 to 27, where lower scores indicate
better outcomes. If 1 question has a missing result, set the missing result to 0 before
summing; if more than 1 question is missing, then the QOLHEQ Treatment and
Prevention subscore cannot be calculated.
•
QOLHEQ Total Score = sum of all 30 QOLHEQ questions. Questions 4, 10, and 28 are
scored such that never = 0, rarely = 1, sometimes = 1, often = 2, and all the time = 3;
otherwise, questions are scored such that never = 0, rarely = 1, sometimes = 2, often = 3,
and all the time = 4. The range for QOLHEQ Total score is 0 to 117, where lower scores
indicate better outcomes. If 1 to 3 questions have a missing result, set the missing result
to 0 before summing; if more than 3 questions are missing, then the QOLHEQ Total
score cannot be calculated.
•
Total Hand % BSA Affected by Disease = sum of % BSA affected by disease from the
following hand areas: left palmar, left dorsal, right palmar, and right dorsal. All 4 hand
areas must have a result for the total hand % BSA affected by disease to be calculated.
•
Compliance = number of applications divided by the expected number of investigational
product (IP) applications for each subject. Compliance will be calculated using drug
accountability data over the entire treatment period for each subject, up to treatment
completion or discontinuation.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 30 of 219
•
Number of Expected IP Applications (BID dosing) = 170 (Cohort 2 BID) for
subjects who complete the study or number of days between first and last application
of IP, derived as 2 * (last treatment date - first treatment date + 1), for subjects who
discontinue early from the study.
•
Number of Expected IP Applications (QD dosing) = 30 (Cohort 1) or 85
(Cohort 2 QD) for subjects who complete the study or number of days between first
and last application of IP, derived as (last treatment date - first treatment date + 1), for
subjects who discontinue early from the study.
•
Number of IP Applications = number of expected IP applications – missed IP
applications as collected in the electronic case report form (eCRF).
•
Weight of IP (g) = returned tube weight – dispensed tube weight.
•
Body Mass Index (BMI) (kg/m2) = [weight (kg) / height (cm) / height (cm)] x 10,000.
•
Change from Baseline = value at current time point – value at baseline.
•
Treatment Emergent AE (TEAE) = any AE with an onset date/time after the first
application of IP. If time is unavailable, any AE occurring on or after the date of first
application of IP will be considered treatment emergent.
•
Completion of Study = Completion of the primary efficacy assessment (IGA) at
Week 12. This may differ than what was recorded in the eCRF.
6.1.8. Data Adjustments/Handling/Conventions
All collected data will be presented in listings. Data not subject to analysis according to this plan
will not appear in any tables or graphs but will be included only in the data listings.
All P values will be displayed in four decimals and rounded using standard scientific notation
(e.g., 0.XXXX). If a P value less than 0.0001 occurs it will be shown in tables as <0.0001;
similarly, if a P value greater than 0.9999 occurs it will be shown in tables as >0.9999.
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA)
version 23.0 thesaurus.
Medications will be coded using the World Health Organization Drug Dictionary Enhanced
(WHO-DDE) Global B3 version September 2019.
A treatment-related AE is any AE with a relationship to the study drug of possibly related,
probably related, likely related, or missing.
For partial AE and medication start dates:
•
If the year is unknown, then do not impute the date but assign a missing value.
•
If the year is known, but the month or month and day is unknown, then:
o If the year matches the year of first dose date and the end date (if present) is after first
dose date, then impute as the month and day of the first dose date.
o Otherwise, assign 01 January.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
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•
If the year and month are known, but the day is unknown, then:
o If the month and year match the month and year of the first dose date, then impute as
the day of the first dose date.
o Otherwise, assign 01.
For partial AE and medication end dates:
•
If the year is unknown, then do not impute the date but assign as missing value.
•
If the year is known, but the month or month and day is unknown, then:
o If the year matches the year of the last date of the study (date of last contact if subject
lost to follow-up; date of completion or early termination otherwise), then impute as
the month and day of the last date of the study.
o Otherwise, assign 31 December.
•
If the year and month are known, but the day is unknown, then:
o If the month and year match the month and year of the last date of the study, then
impute as the day of the last date of the study.
o Otherwise, assign the last day of the month.
These conventions will be applied to AE and medication onset dates and times with the
following precaution: if the missing date and time reflect the date and time of onset of an AE, the
modified date and time will be constructed to match the first documented date/time post drug
administration while preserving the order in which the AE was reported in the eCRF.
In cases where variables for questionnaires were derived in the eCRF (e.g., total scores) and a
derivation is indicated in Section 6.1.7, the results as derived by statistics (as opposed to the
results derived in the eCRF) will be used in analysis.
6.1.9. Presentation of Cohorts and Treatments in Summaries
Study subjects and demographic summaries will be presented by cohort and treatment in the
same output, as follows:
•
Cohorts 1 and 2: Cohort 1 (ARQ-252 cream 0.3% QD); Cohort 2 (ARQ-252 cream 0.3%
QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1% BID, vehicle cream QD, and
vehicle cream BID)
Efficacy data will be presented separately for each cohort (where the efficacy parameter was
collected for subjects in Cohort 1), as follows:
•
Cohort 1: ARQ-252 cream 0.3% QD
•
Cohort 2: ARQ-252 cream 0.3% QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1%
BID, and vehicle cream (all dose frequencies)
•
Cohort 2, Pooled Treatments: ARQ-252 cream (all strengths/dose frequencies), ARQ-252
cream 0.3% (all dose frequencies), and vehicle cream (all dose frequencies)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
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Safety summaries will be presented by cohort and treatment in the same output where possible,
as follows:
•
Cohorts 1 and 2: Cohort 1 (ARQ-252 cream 0.3% QD); Cohort 2 (ARQ-252 cream 0.3%
QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1% BID, vehicle cream QD, and
vehicle cream BID)
Otherwise, safety summaries will be presented separately for each cohort, as follows:
•
Cohort 1: ARQ-252 cream 0.3% QD
•
Cohort 2: ARQ-252 cream 0.3% QD, ARQ-252 cream 0.3% BID, ARQ-252 cream 0.1%
BID, vehicle cream QD, and vehicle cream BID
6.2.
Special Handling for COVID-19 Disruptions
In some cases, study visits will have to be delayed/not performed as a result of COVID-19
disruptions (e.g., sites were closed or subjects were under stay-at-home orders). Where possible,
study sites may collect post-baseline data from subjects remotely by telephone, traditional mail,
and/or email; this will be clearly documented in the source. If possible, sites should adhere to the
protocol visit window for remote data collection.
Investigator assessments and subject questionnaires normally completed during on-site visits
should be completed on the appropriate paper source documents. The following
assessments/questionnaires are approved to be collected via telemedicine/remotely:
•
WI-NRS
•
Pain NRS
•
Subject Local Tolerability
•
QOLHEQ
•
IP / diary compliance
The following assessments cannot be completed via telemedicine/remotely:
•
IGA
•
BSA
•
Investigator Local Tolerability
•
Subject Weight
•
HECSI
•
Nail Dystrophy Assessment


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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Study visits and procedures must be followed per protocol whenever possible. Any specific
changes in study conduct that deviate from the protocol should be communicated to the
institutional review board and Sponsor. All protocol deviations which occurred as a result of
COVID-19 disruptions (e.g., visits out of window, missed assessments, etc.) will be
differentiated from other protocol deviations.
7.
STUDY SUBJECTS AND DEMOGRAPHICS
Presentation of treatments for the study subjects and demographics summary tables are described
in Section 6.1.9.
7.1.
Disposition of Subjects and Withdrawals
Disposition will include tabulations of the number of subjects enrolled (Cohort 1) or randomized
into each treatment group (Cohort 2), the number of subjects who received treatment, subjects
completing the study, tabulated reasons for discontinuation from the study, including whether or
not the subject did not complete the study due to COVID-19 disruption and reasons, and number
of subjects in each analysis population. Disposition will be summarized for all subjects who were
entered into the database by treatment group within cohort. This summary will be based on all
enrolled (Cohort 1) or randomized (Cohort 2) subjects.
7.2.
Protocol Violations and Deviations
The number of subjects with important protocol deviations and/or eligibility deviations will be
summarized in categories by treatment group within cohort for subjects in Safety population; the
incidence of all protocol deviations will also be provided. All protocol deviations will be
provided in the data listings.
7.3.
Demographics and Other Baseline Characteristics
Summary statistics for age, gender (including child-bearing potential), race, ethnicity, height,
weight, percent BSA affected by disease (dorsal [left hand], dorsal [right hand], palmar
[left hand], palmar [right hand], total hand), BMI, and baseline disease characteristics
(IGA, WI-NRS, HECSI subscores and total score, Pain NRS, and QOLHEQ subscores and total
score) will be presented by treatment group within cohort, as well as for overall subjects across
both cohorts.
A summary of chronic hand eczema history, including primary morphologic subtype of hand
eczema, patch test results, and distribution of chronic hand eczema (presence of eczema on each
hand on the following surfaces: palmar [including lateral aspects of fingers], dorsal, interdigital,
and pulpitis) will be presented by treatment group within cohort.
The number and percent of subjects reporting various medical histories, grouped by MedDRA
system organ class and preferred term, will be tabulated by treatment group within cohort.
For the continuous variables, the number of nonmissing values and the mean, SD, minimum,
median and maximum will be tabulated.


Statistical Analysis Plan,
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For ordinal variables such as the IGA, WI-NRS, and Pain NRS, summary statistics including the
mean, median, and range of the ordinal variable will be presented, as well as frequency counts of
each level of the ordinal variable.
For the categorical variables, the counts and proportions of each value will be tabulated.
These analyses will be conducted for the ITT and Safety populations, except for chronic hand
eczema history summary, which will only be summarized on the Safety population.
7.4.
Exposure and Compliance
The number of IP applications by each subject based on diary data will be summarized using
descriptive statistics appropriate for continuous variables.
The amount of IP each subject used based on tube weight will be summarized descriptively by
treatment group using continuous methods.
A subject will be considered compliant with the dosing regimen if the subject applies at least
80% of the expected applications during the IP application period and does not miss more than
3 consecutive days of dosing.
Investigational product application compliance will be calculated based on number of
applications divided by the expected number of IP applications. Compliance will be summarized
descriptively by treatment group using the following categories:
>100%
≥80% - ≤100%
<80%
8.
EFFICACY ANALYSIS
The statistical models described in this section apply to subjects in Cohort 2 (Phase 2b) only,
unless otherwise specified. Presentation of treatments for the efficacy summary tables are
described in Section 6.1.9.
8.1.
Primary Efficacy Analysis
8.1.1. Investigator Global Assessment (IGA) Score of “Clear” or “Almost Clear” at
Week 12
The IGA is a static evaluation of qualitative overall chronic hand eczema severity. This global
assessment scale is an ordinal scale with five severity grades (reported only in integers of 0 to 4).
Each IGA Severity Score is defined by distinct and clinically relevant morphologic descriptions
that minimizes inter-observer variability. Table 7 illustrates the description of each severity
grade.


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Table 7:
IGA
Score
Grade
Description
0
Clear
Absence of erythema and scaling,
AND
Absence of vesiculation, edema, and fissures.
Note: Post-inflammatory pigmentary changes may be present.
1
Almost
clear
Barely perceptible or faint erythema, and/or
Slight flaking over limited areas, mostly fine scales,
AND
Absence of vesiculation, edema, or fissures
2
Mild
Barely perceptible or faint erythema, and/or
Slight flaking over limited areas, mostly fine scales
AND
Scattered vesicles affecting up to 10% of hand, without erosion, and/or
Dermal swelling over less than 10% of hands, and/or
Cracked skin affecting a small area of the hand
3
Moderate
Either barely perceptible or faint erythema, or prominent redness,
and/or
Either slight flaking over limited areas, mostly fine scales, or flaking
over widespread area(s), coarser scale
AND
Scattered or clustered vesicles affecting up to 30% of hand, without
visible erosion or excoriation, and/or
Definite dermal swelling over more than 10% of hand, and/or
Cracked skin affecting multiple areas of the hand
4
Severe
Either prominent or deep intense red color, and/or
Either flaking over widespread area(s), coarser scales, or desquamation
covering over 30% of the hand, with coarse thick scales
AND
At least one of the following:
High density of vesicles extending over large area(s), or with erosion or
excoriation, and/or
Dermal swelling with skin induration over widespread area(s), and/or
One or more deep fissures and causing bleeding


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Categorical Data Analysis
The primary efficacy endpoint is the rate of subjects achieving an IGA score of “Clear” or
“Almost Clear” at Week 12.
The primary statistical comparisons for Cohort 2 subjects will be as follows:
•
ARQ-252 cream 0.3% BID versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.3% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.1% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream (all strengths and dose frequencies) versus vehicle cream (all dose
frequencies)
•
ARQ-252 cream 0.3% (all dose frequencies) versus vehicle cream (all dose frequencies)
The primary endpoint will be analyzed using a CMH test stratified by pooled study site group
and baseline IGA category. Statistical significance will be concluded at the 10% significance
level (2-sided) or less, as discussed in Section 4.1. Odds ratios and 90% and 95% CIs for the
odds ratios will be provided. Additionally, the 90% and 95% Wilson CIs for proportion of
successes in each treatment group will be presented.
For the primary analysis, missing IGA scores will be imputed using multiple imputation as
described in Section 6.1.4. These imputations will result in a minimum of 25 to a maximum of
250 complete analysis datasets, depending on the number of imputed monotone datasets
required. The CMH analyses will be performed separately for each of the complete analysis data
sets, and the results will be combined into one multiple imputation inference (estimated
treatment effect and associated CI and P value).
The primary efficacy analysis will be based on Cohort 2 subjects in the ITT population.
8.1.2. Sensitivity Analyses of the Primary Efficacy Endpoint
The following sensitivity analyses will be performed, based on the CMH test as described in
Section 8.1:
•
The primary efficacy endpoint analysis, repeated on Cohort 2 subjects in the ITT and
PP populations on nonimputed data; and
•
The primary efficacy endpoint analysis (excluding the CMH testing), repeated on
Cohort 1 subjects in the All Treated population on nonimputed data only.


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8.2.
Secondary Efficacy Analysis
All secondary efficacy analyses will be performed using the All Treated population for subjects
in Cohort 1 and the ITT population for subjects in Cohort 2, unless otherwise specified.
The statistical comparisons for all secondary efficacy endpoints for Cohort 2 subjects will be as
follows:
•
ARQ-252 cream 0.3% BID versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.3% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream 0.1% QD versus vehicle cream (all dose frequencies)
•
ARQ-252 cream (all strengths and dose frequencies) versus vehicle cream (all dose
frequencies)
•
ARQ-252 cream 0.3% (all dose frequencies) versus vehicle cream (all dose frequencies)
8.2.1. Investigator Global Assessment (IGA)
Secondary efficacy endpoints relating to the IGA include the following:
•
The rate of achievement of IGA of “clear” or “almost clear” PLUS at least a 2-point
improvement from Baseline at Weeks 2, 4, 8, 12, and 13
•
The rate of achievement of at least a 2-point improvement from baseline at Weeks 2, 4, 8,
12, and 13
•
The rate of achievement of IGA of “clear” or “almost clear” at Weeks 2, 4, 8, and 13
•
Change in IGA score at Weeks 2, 4, 8, 12, and 13 as compared to baseline
Rate of Achievement Analyses
Rate of achievement analyses will be performed using the same CMH test as described in
Section 8.1 as follows:
•
The rate of achievement of IGA of “clear” or “almost clear” PLUS at least a 2-point
improvement from baseline will be analyzed on Cohort 2 subjects in the ITT population
(imputed and nonimputed data) and PP population (nonimputed data only);
•
The rate of achievement of at least a 2-point improvement from baseline will be analyzed
on Cohort 2 subjects in the ITT population (imputed and nonimputed data); and
•
The rate of achievement of IGA of “clear” or “almost clear” will be analyzed on Cohort 2
subjects in the ITT population (imputed and nonimputed data) and PP population
(nonimputed data only).
Rate of achievement of IGA success (IGA score of “clear” or “almost clear” plus at least a
2-point improvement from baseline) will also be analyzed by baseline IGA score, for Cohort 2
subjects in the ITT population (imputed and nonimputed data). The proportion of subjects
achieving IGA success at Week 12 will be presented by study site for Cohort 2 subjects in the
ITT population (nonimputed data only). Additionally, a summary will be provided for subjects in


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Cohort 1 in the All Treated population (nonimputed data only), however, this will not include the
CMH test.
Change in IGA Score Analysis
Change and percent change from baseline to Weeks 2, 4, 8, 12, and 13 in IGA score will be
analyzed using descriptive summaries and an analysis of covariance (ANCOVA) with terms for
treatment group, pooled site group, and baseline IGA category as covariates, by study visit.
Statistical comparisons between the treatment groups will be obtained using contrasts. The least-
squares (LS) means, standard errors, 90% and 95% CIs, and P values will be presented. These
summaries will be provided for Cohort 2 subjects in the ITT population (imputed and
nonimputed data) and PP population (ANCOVA using nonimputed data only). Additionally, this
analysis will be repeated for Cohort 1 subjects in the All Treated population, excluding between-
treatment contrasts (due to being a single-treatment cohort).
8.2.2. Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score
Secondary efficacy endpoints relating to WI-NRS pruritus score include the following:
•
Change and percent change in WI-NRS pruritus score at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, and 13 as compared to Baseline
•
The rate of achievement of ≥4-point reduction from Baseline in WI-NRS pruritus score at
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first study drug application, in
subjects with Baseline WI-NRS pruritus score of at least 4
Change in WI-NRS Pruritus Score Analysis
Change and percent change from baseline to each study week through Week 12 in average
weekly WI-NRS pruritus score will be analyzed using descriptive statistics and an ANCOVA
with terms for treatment group, pooled site group, baseline IGA category, and baseline WI-NRS
pruritus score as covariates, by study visit. Statistical comparisons between the treatment groups
will be obtained using contrasts. The LS means, standard errors, 90% and 95% CIs, and P values
will be presented. This analysis will be based on Cohort 2 subjects in the ITT and PP populations
(ANCOVA using nonimputed data only). Additionally, this analysis will be repeated for Cohort
1 subjects in the All Treated population, excluding between-treatment contrasts (due to being a
single-treatment cohort).
Rate of Achievement Analysis
In subjects with a baseline WI-NRS score ≥4, achievement of a ≥4-point improvement from
baseline in average weekly WI-NRS score at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13
will be analyzed using CMH tests stratified by pooled site group and baseline IGA category
similar to the primary analysis in Section 8.1, with the exception that missing data will not be
replaced. Odds ratios and 90% and 95% CIs of the odds ratios will be provided. Additionally, the
90% and 95% Wilson CIs for proportion of successes in each treatment group will be presented.
This analysis will be based on Cohort 2 subjects in the PRU4 population (nonimputed data only).


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Additionally, this analysis will be repeated for Cohort 1 subjects in the All Treated population,
excluding the CMH test (due to being a single-treatment cohort).
8.2.3. Hand Eczema Severity Index (HECSI)
The secondary efficacy endpoints relating to HECSI are:
•
Change and percent change in HECSI score at Weeks 2, 4, 8, 12, and 13 compared to
Baseline
•
Achievement of HECSI-75
The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand
eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total
HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and
a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100%
affected area). Derivations for each of the subscores and the total score can be found in
Section 6.1.7.
Change and percent change from baseline to Weeks 2, 4, 8, 12, and 13 in HECSI subscores
(Fingertips, Fingers [except Tips], Palm of Hands, Back of Hands, and Wrists) and total score
will be analyzed using descriptive statistics and an ANCOVA with terms for treatment group,
pooled site group, baseline IGA category, and baseline HECSI score as covariates, by study visit.
Statistical comparisons between the treatment groups will be obtained using contrasts. The LS
means, standard errors, 90% and 95% CIs, and P values will be presented. This analysis will be
based on Cohort 2 subjects in the ITT population (nonimputed data only) and PP population
(ANCOVA using nonimputed data only). Additionally, this analysis will be repeated for Cohort
1 subjects in the All Treated population, excluding between-treatment contrasts (due to being a
single-treatment cohort).
Frequencies and percentages of subjects achieving HECSI-75 will be presented by study vist and
treatment group. This endpoint will be analyzed using CMH tests stratified by pooled site group
and baseline IGA category similar to the primary analysis in Section 8.1, with the exception that
missing data will not be replaced. Odds ratios and 90% and 95% CIs of the odds ratios will be
provided. Additionally, the 90% and 95% Wilson CIs for proportion of subjects achieving 75%
reduction in each treatment group will be presented. This analysis will be based on Cohort 2
subjects in the ITT and PP populations (nonimputed data only).
8.2.4. Pain Numeric Rating Scale (NRS) Score
Secondary efficacy endpoints relating to Pain NRS score include the following:
•
Change and percent change in Pain NRS score from Baseline to Weeks 1, 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, and 13
•
The rate of achievement of ≥4-point reduction from Baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug with Baseline
Pain NRS score of at least 4


Statistical Analysis Plan,
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•
The rate of achievement of ≥3-point reduction from Baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 3
•
The rate of achievement of ≥2-point reduction from Baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 2
The Pain NRS score is the subject’s assessment of worst pain intensity over the past 24 hours on
a scale of 0 to 10, where 0 = “no pain” and 10 = “worst possible pain”.
Change in Pain NRS Score Analysis
Change and percent from baseline to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first
application of study drug in average weekly Pain NRS score will be analyzed using descriptive
statistics and an ANCOVA with terms for treatment group, pooled site group, baseline IGA
category, and baseline Pain NRS score as covariates, by study visit. Statistical comparisons
between the treatment groups will be obtained using contrasts. The LS means, standard errors,
90% and 95% CIs, and P values will be presented. This analysis will be based on Cohort 2
subjects in the ITT population (nonimputed data only). Additionally, this analysis will be
repeated for Cohort 1 subjects in the All Treated population, excluding between-treatment
contrasts (due to being a single-treatment cohort).
Rate of Achievement Analysis
In subjects with a baseline Pain NRS score ≥4, achievement of a ≥4-point improvement from
baseline in average weekly Pain NRS score at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks
after first application of study drug will be analyzed using CMH tests stratified by pooled site
group and baseline IGA category similar to the primary analysis in Section 8.1, with the
exception that missing data will not be replaced. Odds ratios and 90% and 95% CIs of the odds
ratios will be provided. Additionally, the 90% and 95% Wilson CIs for proportion of successes
in each treatment group will be presented. This analysis will be based on Cohort 2 subjects in the
PNRS4 population (nonimputed data only). Additionally, this analysis will be repeated for
Cohort 1 subjects in the PNRS4 population, excluding the CMH test (due to being a single-
treatment cohort).
This analysis will furthermore be repeated on subjects with a baseline Pain NRS score ≥3 and a
baseline Pain NRS score ≥2 for achievement of a ≥3-point improvement from baseline and a
≥2-point improvement from baseline, respectively. This analysis will be performed on subjects in
the PNRS3 and PNRS2 populations, with each cohort presented separately (where the CMH
testing in Cohort 1 will be excluded).


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8.2.5. Quality of Life in Hand Eczema Questionnaire (QOLHEQ)
The secondary efficacy endpoint relating to QOLHEQ is:
•
Change and percent change from baseline in overall QOLHEQ score at each study visit
The construct HRQOL includes all impairments or limiting conditions caused by the health state
of an individual. The QOLHEQ is a disease specific instrument, thereby only assessing
impairments caused by hand eczema. It consists of 30 items which can be summarized according
to four domains of HRQOL: Impairments because of (1) symptoms, (2) emotions, (3) limitations
in functioning, or (4) because of treatment and prevention. Derivations for each of the subscores
and the total score can be found in Section 6.1.7.
Change and percent change from baseline to Weeks 2, 4, 8, 12, and 13 in QOLHEQ subscores
(Symptoms, Emotions, Limitations in Function, Treatment and Prevention) and total score will
be analyzed using descriptive statistics and an ANCOVA with terms for treatment group, pooled
site group, baseline IGA category, and baseline overall QOLHEQ score as covariates, by study
visit. Statistical comparisons between the treatment groups will be obtained using contrasts. The
LS means, standard errors, 90% and 95% CIs, and P values will be presented. These analyses
will be based on Cohort 2 subjects in the ITT population (nonimputed data only).
8.2.6. Percent Body Surface Area (BSA) Affected by Disease
The secondary efficacy endpoint relating to percent BSA affected by disease (dorsal [left hand],
dorsal [right hand], palmar [left hand], palmar [right hand], total hand) is:
•
Percent BSA affected by disease and % change from baseline in BSA affected by disease
at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 13 weeks
Change and percent change from baseline to Weeks 2, 4, 8, 12, and 13 in percent BSA affected
by disease will be analyzed using descriptive statistics and an ANCOVA with terms for
treatment group, pooled site group, baseline IGA category, and baseline percent BSA affected by
disease as covariates, by study visit. Statistical comparisons between the treatment groups will be
obtained using contrasts. The LS means, standard errors, 90% and 95% CIs, and P values will be
presented. This analysis will be based on Cohort 2 subjects in the ITT population
(nonimputed data only). Additionally, this analysis will be repeated for Cohort 1 subjects in the
All Treated population, excluding between-treatment contrasts (due to being a single-treatment
cohort).


Statistical Analysis Plan,
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Protocol Number ARQ-252-205
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8.3.
Exploratory Efficacy Analysis
The exploratory efficacy endpoint is:
•
Change from Baseline in Nail Dystrophy at each visit
In subjects with a nail dystrophy at baseline, change in number of millimeters of normal-
appearing nail distal to the cuticle will be summarized by treatment group and study visit. Since
the number if millimeters of normal-appearing nail distal to the cuticle at baseline was not
collected, it is assumed to be 0 mm; similarly, for subjects with nail dystrophy at baseline, if they
report having no normal-appearing nail distal to the cuticle after baseline, their result is imputed
as 0 mm (as this amount is not collected in the eCRF). This analysis will be based on Cohort 2
subjects in the ND population (nonimputed data only).
9.
SAFETY AND TOLERABILITY ANALYSIS
Safety will be evaluated from reported AEs, physical examinations, local tolerability
assessments, changes in clinical laboratory values, and changes in vital signs/weight. No
inferential statistical tests will be performed.
All safety analyses will be performed on the Safety population.
Presentation of treatments for safety analysis summary tables are described in Section 6.1.9.
9.1.
Adverse Events
All AEs, TEAEs, and SAEs will be coded using the MedDRA dictionary version 23.0.
A TEAE is defined as an AE within an onset on or after the day of study treatment through study
completion. An overall summary of TEAEs will be provided; this will present number and
percent of subjects who reported at least 1 of the following: TEAE (including all TEAEs, TEAEs
by maximum severity, and related TEAEs), SAE, discontinued the study due to a TEAE,
discontinued the study drug due to a TEAE, or a TEAE resulting in death.
The number and percent of subjects reporting TEAEs, grouped by MedDRA system organ class
(SOC) and preferred term, will be tabulated by severity or by greatest relationship to study drug
and treatment group within cohort. In the case of multiple occurrences of the same TEAE within
the same subject, each subject will only be counted once for each preferred term. Additionally,
the number and percent of subjects reporting related TEAEs will be summarized by MedDRA
SOC, preferred term, severity, and treatment group within cohort.
Relationship to study drug will be mapped as follows: related = likely related, probably related,
or possibly related; unrelated = unlikely related or unrelated. In the summaries showing severity
and relationship to study medication the event with the maximum severity (mild < moderate
< severe < life-threatening < death) or strongest relationship (unrelated < related) will be
reported. If a particular event is missing the severity and/or relationship, then the strongest
possible severity or relationship will be assumed for analysis (severity = severe,
relationship = related).


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In the AE data listings, all AEs will be displayed. Any AEs that are treatment emergent will be
flagged.
9.1.1. Adverse Events Leading to Withdrawal
A summary of incidence rates (frequencies and percentages) of TEAEs leading to withdrawal of
study drug by treatment group within cohort, SOC, and preferred term will be prepared for the
Safety population. Additionally, this table will be repeated for related TEAEs leading to
withdrawal of study drug and all TEAEs leading to withdrawal from the study. No inferential
statistical tests will be performed.
A data listing of AEs leading to withdrawal of study drug will also be provided, displaying
details of the event(s) captured on the eCRF.
9.1.2. Deaths and Serious Adverse Events
Any deaths that occur during the study will be listed.
Serious adverse events (SAEs) will be listed and tabulated by SOC and preferred term and
presented by treatment group within cohort, by severity, and by relationship to study treatment.
9.2.
Local Tolerability Assessments
The investigator’s assessment of the application site reaction will be summarized by study visit
and treatment group within cohort using both categorical methods (number and percentage of
subjects with each score) as well as continuous methods (e.g., mean, median). Categorical
summaries will be provided for dermal response as well as other effects. No inferential statistical
tests will be performed.
The subject’s assessment of the application site reaction will be summarized similarly.
9.3.
Clinical Laboratory Evaluations
Laboratory test results will be summarized descriptively by treatment and study visit as both
observed values and change from baseline values for continuous hematology, chemistry
(including thyroid), and urinalysis results. Categorical urinalysis results will be summarized
using frequencies by study visit and treatment group within cohort.
The number of subjects with clinical laboratory values below, within, or above the normal range
by study visit and in relation to baseline will be tabulated for each clinical laboratory analyte by
treatment group within cohort (shift table).
Abnormal results will be flagged in the listings. In addition, pregnancy test results and hormonal
laboratory results will be listed.


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PCN Number ARCU211360
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9.4.
Vital Signs
Descriptive summaries of observed values and changes from baseline will be calculated for
systolic blood pressure, diastolic blood pressure, heart rate, height, weight, BMI, and oral body
temperature by treatment group within cohort and study visit.
9.5.
12-Lead Electrocardiograms
Descriptive summaries for observed values and change from baseline will be presented for
12-lead electrocardiogram (ECG) measures of PR interval, QRS interval, QT interval, QTc
interval (Fridericia’s [QTcF] correction method), and heart rate. These summaries will be
presented by study visit and treatment group within cohort.
The number and percentage of subjects with each ECG investigator interpretation (normal;
abnormal, not clinically significant; or abnormal, clinically significant) will be displayed for each
treatment group within cohort and study visit.
9.6.
Physical Examination
The number and percentage of subjects with normal and abnormal findings in the physical
examination will be displayed at each study visit and treatment group within cohort.
9.7.
Concomitant Medications
Prior and concomitant medications will be summarized descriptively by treatment within cohort,
Anatomical Therapeutic Chemical (ATC) Class Level 4, and Preferred Term using counts and
percentages.
Prior medications will be presented separately from concomitant medications. Medications that
started before the first application of IP will be considered prior medications whether or not they
were stopped before the first application of study drug. Any medications continuing or starting
after the first application of study drug will be considered to be concomitant. If a medication
starts before the first application of study drug and continues after the first application of study
drug it will be considered both prior and concomitant.
9.8.
Modified Total Lesion Symptom Score (mTLSS)
The modified Total Lesion Symptom Score (mTLSS) is used to determine the intensity of
features as part of the IGA Severity Score. The total mTLSS is calculated as the sum of scores
(0 = absent, 1 = mild, 2 = moderate, 3 = severe) assigned by the investigator for the chronic hand
eczema parameters.
This endpoint was removed from the protocol as of amendment 1 (11May2020), thus a limited
number of subjects and visits had data collected. The mTLSS results will be listed only.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 45 of 219
10.
CHANGES FROM PLANNED ANALYSIS
The following analysis populations have been added:
•
The PRU4 population has been added to facilitate WI-NRS analysis on the ITT
population;
•
The PNRS4, PNRS3, and PNRS2 populations have been added to facilitate Pain NRS
analysis for subjects achieving a 4-point, 3-point, and 2-point reduction from baseline,
respectively; and
•
The All Treatment population has been added to facilitate Cohort 1 efficacy analyses.
•
The ND population has been added to facilitate Cohort 2 analyses of nail dystrophy.
These populations are not included in the protocol.
The exploratory endpoint is change from baseline in nail dystrophy; since no baseline
measurement will be collected for millimeters of normal nail distal to cuticle, it will be assumed
that the amount of normal nail at baseline is 0 mm.
The definition of compliance was updated to exclude subjects who missed more than
3 consecutive days of dosing, versus subjects who missed more than 3 consecutive doses.
The following secondary endpoints were added upon request by the Sponsor:
•
The rate of achievement of IGA of “clear” or “almost clear” PLUS at least a 2-point
improvement from Baseline at Week 13
•
The rate of achievement of at least a 2-point improvement from baseline at Week 13
•
The rate of achievement of IGA of “clear” or “almost clear” at Week 13
•
Change in IGA score at Week 13 as compared to baseline
•
Change in WI-NRS pruritus score at 1, 3, 5, 6, 7, 9, 10, 11, and 13 compared to baseline
(Weeks 2, 4, 8, and 12 were already included)
•
Percent change in WI-NRS pruritus score at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and
13 weeks after first application of study drug compared to baseline
•
Change and percent change in HECSI score at Weeks 2, 4, 8, 12, and 13 compared to
baseline
•
Achievement of HECSI-75
•
Percent change in Pain NRS score from Baseline to at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,
and 13 weeks after first application of study drug
•
The rate of achievement of ≥3-point reduction from baseline in Pain NRS score at 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug in subjects
with baseline Pain NRS score of at least 3
•
The rate of achievement of ≥2-point reduction from baseline in Pain NRS score 1, 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, and 13 weeks after first application of study drug weeks in
subjects with baseline Pain NRS score of at least 2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 46 of 219
•
Percent change from baseline in QOLHEQ score at each visit
The following treatment comparisons were added:
•
ARQ-252 cream (all strengths and dose frequencies) versus vehicle cream (all dose
frequencies)
•
ARQ-252 cream 0.3% (all dose frequencies) versus vehicle cream (all dose frequencies)
For all efficacy treatment comparisons, vehicle cream will be pooled for analysis over both dose
frequencies.
Efficacy analysis for Cohort 1 was not specified in the protocol, however, upon request from
Sponsor, all efficacy data collected for Cohort 1 (IGA, HECSI, average weekly WI-NRS,
average weekly Pain NRS, and % BSA affected by disease) will be summarized.
Subgroup analyses for IGA Success by study site (Week 12 only) and by baseline IGA severity
were added.
An analysis of HECSI-75 and total % BSA affected by disease were also requested to be added.
All analyses of time to event (i.e., time to IGA of “clear” or “almost clear”; time to the first
achievement of ≥4-point reduction from Baseline in WI-NRS pruritus score in subjects with
Baseline WI-NRS pruritus score of at least 4; and time to the first achievement of ≥4-point
reduction from Baseline in Pain NRS score in subjects with Baseline Pain NRS score of at least
4) were removed at the request of the sponsor.
11.
OTHER PLANNED ANALYSIS
11.1.
Pharmacokinetic Analysis
All PK collection information from the eCRF will be presented in a listing. Concentration data
and PK parameters will be summarized by time point (concentration data), study visit, and
treatment group within cohort using summary statistics. In addition, PK concentration and
parameter listings will be presented.
12.
REFERENCES
ASA. (2018) Ethical Guidelines for Statistical Practice. Prepared by the Committee on
Professional Ethics, April 2018. http://www.amstat.org/about/ethicalguidelines.cfm
ICH (1998). ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9;
1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf
RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014.
https://rss.org.uk/about/policy-and-guidelines/code-of-conduct/
Ratitch, B., Lipkovich, I., & O’Kelly, M. (2013). Combining Analysis Results from Multiply
Imputed Categorical Data.
PharmaSUG. https://www.pharmasug.org/proceedings/2013/SP/PharmaSUG-2013-SP03.pdf


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 47 of 219
13.
TABLES, LISTINGS, AND FIGURES
All TLFs will have a header showing the sponsor company name and protocol and a footer
showing the version of SAS, the file name and path, and the source of the data (e.g., listing
number).
13.1.
Planned Table Descriptions
The following are planned summary tables for protocol number ARQ-252-205. The table
numbers and page numbers are place holders only and will be determined when the tables are
produced.
13.1.1. Demographic Data
Table 8:
Demographic Data Summary Tables and Figures
Table Number
Population
Table Title / Summary
Table 14.1.1
All Randomized
Cohorts 1 and 2: Summary of Subject Disposition
Table 14.1.2.1
Safety
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Table 14.1.2.2
ITT
Cohort 2: Summary of Demographics and Baseline Characteristics
Table 14.1.3.1
Safety
Cohorts 1 and 2: Summary of Medical History by System Organ Class
and Preferred Term
Table 14.1.3.2
Safety
Cohorts 1 and 2: Summary of Chronic Hand Eczema Medical History
Table 14.1.4
Safety
Cohorts 1 and 2: Summary of Protocol Deviations
Table 14.1.5
Safety
Cohorts 1 and 2: Summary of Prior Medications by ATC Class Level 4
and Preferred Term
Table 14.1.6
Safety
Cohorts 1 and 2: Summary of Study Drug Exposure and Compliance


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 48 of 219
13.1.2. Efficacy Data
Table 9:
Efficacy Data
Table Number
Population
Table Title / Summary
Table 14.2.1.1.1
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades and
Score of “Clear” or “Almost Clear” by Study Visit – Multiple Imputation
Categorical Results
Table 14.2.1.1.2
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by
Study Visit – Multiple Imputation
Categorical Results
Table 14.2.1.2.1
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades
Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
Table 14.2.1.2.2
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Grades Score of “Clear” or “Almost Clear” by Study
Visit – Observed Data
Categorical Results
Table 14.2.1.2.3
PP
Cohort 2: Summary of Investigator Global Assessment (IGA)
Grades Score of “Clear” or “Almost Clear” by Study Visit – Observed
Data
Categorical Results
Table 14.2.1.2.4
PP
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Grades Score of “Clear” or “Almost Clear” by Study
Visit – Observed Data
Categorical Results
Table 14.2.1.2.5
All Treated
Cohort 1: Summary of Investigator Global Assessment (IGA) Grades
Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
Table 14.2.1.3.1
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit – Multiple Imputation
Categorical Results
Table 14.2.1.3.2
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-
point Improvement from Baseline) by Study Visit – Multiple Imputation
Categorical Results
Table 14.2.1.3.3
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit and Baseline IGA Score – Multiple Imputation
Categorical Results


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 49 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.1.3.4
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus
≥2-point Improvement from Baseline) by Study Visit and Baseline IGA
Score – Multiple Imputation
Categorical Results
Table 14.2.1.3.5
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit – Observed Data
Categorical Results
Table 14.2.1.3.6
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus
≥2-point Improvement from Baseline) by Study Visit – Observed Data
Categorical Results
Table 14.2.1.3.7
PP
Cohort 2: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit – Observed Data
Categorical Results
Table 14.2.1.3.8
PP
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus
≥2-point Improvement from Baseline) by Study Visit – Observed Data
Categorical Results
Table 14.2.1.3.9
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit and Baseline IGA Score – Observed Data
Categorical Results
Table 14.2.1.3.10
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus
≥2-point Improvement from Baseline) by Study Visit and Baseline IGA
Score – Observed Data
Categorical Results
Table 14.2.1.3.11
ITT
Cohort 2: Summary of Proportion of Subjects Achieving Investigator
Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear”
plus ≥2-point Improvement from Baseline) at Week 12 by Study Site –
Observed Data
Categorical Results
Table 14.2.1.3.12
ITT
Cohort 2, Pooled Treatments: Summary of Proportion of Subjects
Achieving Investigator Global Assessment (IGA) Success (Score of
“Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline) at
Week 12 by Study Site – Observed Data
Categorical Results


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 50 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.1.3.13
All Treated
Cohort 1: Summary of Investigator Global Assessment (IGA) Success
(Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from
Baseline) by Study Visit – Observed Data
Categorical Results
Table 14.2.1.4.1
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) ≥2-point
Improvement from Baseline by Study Visit – Multiple Imputation
Categorical Results
Table 14.2.1.4.2
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit –
Multiple Imputation
Categorical Results
Table 14.2.1.4.3
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) ≥2-point
Improvement from Baseline by Study Visit – Observed Data
Categorical Results
Table 14.2.1.4.4
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit –
Observed Data
Categorical Results
Table 14.2.1.4.5
All Treated
Cohort 1: Summary of Investigator Global Assessment (IGA) ≥2-point
Improvement from Baseline by Study Visit – Observed Data
Categorical Results
Table 14.2.1.5.1
ITT
Cohort 2: Summary and Change from Baseline in Investigator Global
Assessment (IGA) Grades by Study Visit – Multiple Imputation
Table 14.2.1.5.2
ITT
Cohort 2, Pooled Treatments: Summary and Change from Baseline in
Investigator Global Assessment (IGA) Grades by Study Visit – Multiple
Imputation
Table 14.2.1.5.3
ITT
Cohort 2: Summary and Change from Baseline in Investigator Global
Assessment (IGA) Grades by Study Visit – Observed Data
Table 14.2.1.5.4
ITT
Cohort 2, Pooled Treatments: Summary and Change from Baseline in
Investigator Global Assessment (IGA) Grades by Study Visit – Observed
Data
Table 14.2.1.5.5
All Treated
Cohort 1: Summary and Change from Baseline in Investigator Global
Assessment (IGA) Grades by Study Visit – Observed Data
Table 14.2.1.6.1
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades by
Study Visit – Multiple Imputation – ANCOVA
Table 14.2.1.6.2
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Grades by Study Visit – Multiple Imputation –
ANCOVA


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 51 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.1.6.3
ITT
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades by
Study Visit – Observed Data – ANCOVA
Table 14.2.1.6.4
ITT
Cohort 2, Pooled Treatments: Summary of Investigator Global
Assessment (IGA) Grades by Study Visit – Observed Data – ANCOVA
Table 14.2.1.6.5
All Treated
Cohort 1: Summary of Investigator Global Assessment (IGA) Grades by
Study Visit – Observed Data – ANCOVA
Table 14.2.2.1.1
ITT
Cohort 2: Summary and Change and Percent Change from Baseline in
Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus
Scores by Study Visit
Table 14.2.2.1.2
ITT
Cohort 2, Pooled Treatments: Summary and Change and Percent Change
from Baseline in Average Weekly Worst Itch – Numeric Rating Scale
(WI-NRS) Pruritus Scores by Study Visit
Table 14.2.2.1.3
ITT
Cohort 2: Summary of Average Weekly Worst Itch – Numeric Rating
Scale (WI-NRS) Pruritus Scores by Study Visit – ANCOVA
Table 14.2.2.1.4
ITT
Cohort 2, Pooled Treatments: Summary of Average Weekly Worst Itch –
Numeric Rating Scale (WI-NRS) Pruritus Scores by Study Visit –
ANCOVA
Table 14.2.2.1.5
PP
Cohort 2: Summary of Average Weekly Worst Itch – Numeric Rating
Scale (WI-NRS) Pruritus Scores by Study Visit – ANCOVA
Table 14.2.2.1.6
PP
Cohort 2, Pooled Treatments: Summary of Average Weekly Worst Itch –
Numeric Rating Scale (WI-NRS) Pruritus Scores by Study Visit –
ANCOVA
Table 14.2.2.1.7
PRU4
Cohort 2: Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS)
Pruritus Score Success (≥4-point Reduction from Baseline) by Study
Visit
Table 14.2.2.1.8
PRU4
Cohort 2, Pooled Treatments: Average Weekly Worst Itch – Numeric
Rating Scale (WI-NRS) Pruritus Score Success (≥4-point Reduction from
Baseline) by Study Visit
Table 14.2.2.1.9
All Treated
Cohort 1: Summary and Change and Percent Change from Baseline in
Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus
Scores by Study Visit
Table 14.2.2.1.10
All Treated
Cohort 1: Summary of Average Weekly Worst Itch – Numeric Rating
Scale (WI-NRS) Pruritus Scores by Study Visit – ANCOVA
Table 14.2.2.1.11
PRU4
Cohort 1: Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS)
Pruritus Score Success (≥4-point Reduction from Baseline) by Study
Visit
Table 14.2.2.2.1
ITT
Cohort 2: Summary and Change and Percent Change from Baseline in
Hand Eczema Severity Index (HECSI) Subscores and Total Score by
Study Visit


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 52 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.2.2.2
ITT
Cohort 2, Pooled Treatments: Summary and Change and Percent Change
from Baseline in Hand Eczema Severity Index (HECSI) Subscores and
Total Score by Study Visit
Table 14.2.2.2.3
ITT
Cohort 2: Summary of Hand Eczema Severity Index (HECSI) Subscores
and Total Score by Study Visit – ANCOVA
Table 14.2.2.2.4
ITT
Cohort 2, Pooled Treatments: Summary of Hand Eczema Severity Index
(HECSI) Subscores and Total Score by Study Visit – ANCOVA
Table 14.2.2.2.5
PP
Cohort 2: Summary of Hand Eczema Severity Index (HECSI) Subscores
and Total Score by Study Visit – ANCOVA
Table 14.2.2.2.6
PP
Cohort 2, Pooled Treatments: Summary of Hand Eczema Severity Index
(HECSI) Subscores and Total Score by Study Visit – ANCOVA
Table 14.2.2.2.7
ITT
Cohort 2: Summary of Achievement of HECSI-75 by Study Visit
Table 14.2.2.2.8
ITT
Cohort 2, Pooled Treatments: Summary of Achievement of HECSI-75 by
Study Visit
Table 14.2.2.2.9
PP
Cohort 2: Summary of Achievement of HECSI-75 by Study Visit
Table 14.2.2.2.10
PP
Cohort 2, Pooled Treatments: Summary of Achievement of HECSI-75 by
Study Visit
Table 14.2.2.2.11
All Treated
Cohort 1: Summary and Change and Percent Change from Baseline in
Hand Eczema Severity Index (HECSI) Subscores and Total Score by
Study Visit
Table 14.2.2.2.12
All Treated
Cohort 1: Summary of Hand Eczema Severity Index (HECSI) Subscores
and Total Score by Study Visit – ANCOVA
Table 14.2.2.3.1
ITT
Cohort 2: Summary and Change and Percent Change from Baseline in
Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Visit
Table 14.2.2.3.2
ITT
Cohort 2, Pooled Treatments: Summary and Change and Percent Change
from Baseline in Average Weekly Pain Numeric Rating Scale (NRS)
Score by Study Visit
Table 14.2.2.3.3
ITT
Cohort 2: Summary of Average Weekly Pain Numeric Rating Scale
(NRS) Score by Study Visit – ANCOVA
Table 14.2.2.3.4
ITT
Cohort 2, Pooled Treatments: Summary of Average Weekly Pain
Numeric Rating Scale (NRS) Score by Study Visit – ANCOVA
Table 14.2.2.3.5
PNRS4
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥4-point Reduction from Baseline) by Study Visit
Table 14.2.2.3.6
PNRS4
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating
Scale (NRS) Score Success (≥4-point Reduction from Baseline) by Study
Visit
Table 14.2.2.3.7
PNRS3
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥3-point Reduction from Baseline) by Study Visit


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 53 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.2.3.8
PNRS3
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating
Scale (NRS) Score Success (≥3-point Reduction from Baseline) by Study
Visit
Table 14.2.2.3.9
PNRS2
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥2-point Reduction from Baseline) by Study Visit
Table 14.2.2.3.10
PNRS2
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating
Scale (NRS) Score Success (≥2-point Reduction from Baseline) by Study
Visit
Table 14.2.2.3.11
All Treated
Cohort 1: Summary and Change and Percent Change from Baseline in
Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Visit
Table 14.2.2.3.12
All Treated
Cohort 1: Summary of Average Weekly Pain Numeric Rating Scale
(NRS) Score by Study Visit – ANCOVA
Table 14.2.2.3.13
PNRS4
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥4-point Reduction from Baseline) by Study Visit
Table 14.2.2.3.14
PNRS3
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥3-point Reduction from Baseline) by Study Visit
Table 14.2.2.3.15
PNRS2
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score
Success (≥2-point Reduction from Baseline) by Study Visit
Table 14.2.2.4.1
ITT
Cohort 2: Summary and Change and Percent Change from Baseline in
Quality of Life in Hand Eczema Questionnaire (QOLHEQ) Subscores
and Total Score by Study Visit
Table 14.2.2.4.2
ITT
Cohort 2, Pooled Treatments: Summary and Change and Percent Change
from Baseline in Quality of Life in Hand Eczema Questionnaire
(QOLHEQ) Subscores and Total Score by Study Visit
Table 14.2.2.4.3
ITT
Cohort 2: Summary of Quality of Life in Hand Eczema Questionnaire
(QOLHEQ) Total Score by Study Visit – ANCOVA
Table 14.2.2.4.4
ITT
Cohort 2, Pooled Treatments: Summary of Quality of Life in Hand
Eczema Questionnaire (QOLHEQ) Total Score by Study Visit –
ANCOVA
Table 14.2.2.5.1
ITT
Cohort 2: Summary and Change and Percent Change from Baseline in %
Body Surface Area (BSA) Affected by Disease by Study Visit
Table 14.2.2.5.2
ITT
Cohort 2, Pooled Treatments: Summary and Change and Percent Change
from Baseline in % Body Surface Area (BSA) Affected by Disease by
Study Visit
Table 14.2.2.5.3
ITT
Cohort 2: Summary of % Body Surface Area (BSA) Affected by Disease
by Study Visit – ANCOVA
Table 14.2.2.5.4
ITT
Cohort 2, Pooled Treatments: Summary of % Body Surface Area (BSA)
Affected by Disease by Study Visit – ANCOVA


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 54 of 219
Table 9:
Efficacy Data (Continued)
Table Number
Population
Table Title / Summary
Table 14.2.2.5.5
All Treated
Cohort 1: Summary and Change and Percent Change from Baseline in %
Body Surface Area (BSA) Affected by Disease by Study Visit
Table 14.2.2.5.6
All Treated
Cohort 1: Summary of % Body Surface Area (BSA) Affected by Disease
by Study Visit – ANCOVA
Table 14.2.3.1
ND
Cohort 2: Summary of Nail Dystrophy Normal-Appearing Nail Distal to
Cuticle (mm) by Study Visit
Table 14.2.3.2
ND
Cohort 2, Pooled Treatments: Summary of Nail Dystrophy Normal-
Appearing Nail Distal to Cuticle (mm) by Study Visit


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 55 of 219
13.1.3. Safety Data
13.1.3.1. Displays of Adverse Events
Table 10:
Safety Data
Table Number
Population
Table Title / Summary
Table 14.3.1.1
Safety
Cohorts 1 and 2: Summary of Treatment Emergent Adverse Events
Table 14.3.1.2
Safety
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by
System Organ Class and Preferred Term
Table 14.3.1.3
Safety
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by
System Organ Class, Preferred Term, and Maximum Severity
Table 14.3.1.4
Safety
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by
System Organ Class, Preferred Term, and Relationship to Study Drug
Table 14.3.1.5
Safety
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events
Leading to Study Drug Discontinuation by System Organ Class and
Preferred Term
Table 14.3.1.6
Safety
Cohorts 1 and 2: Incidence of Related Treatment Emergent Adverse
Events Leading to Study Drug Discontinuation by System Organ Class
and Preferred Term
Table 14.3.1.7
Safety
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events
Leading to Study Discontinuation by System Organ Class and Preferred
Term
Table 14.3.1.8
Safety
Cohorts 1 and 2: Incidence of Related Treatment Emergent Adverse
Events by System Organ Class, Preferred Term, and Maximum Severity
13.1.3.2. Summary of Deaths, Other Serious and Significant Adverse Events
Table Number
Population
Table Title / Summary
Table 14.3.2.1
Safety
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ
Class and Preferred Term
Table 14.3.2.2
Safety
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ
Class, Preferred Term, and Maximum Severity
Table 14.3.2.3
Safety
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ
Class, Preferred Term, and Relationship to Study Drug
13.1.3.3. Narratives of Deaths, Other Serious and Certain Other Significant Adverse
Events
Table Number
Population
Table Title / Summary
Table 14.3.3.1
Safety
Listing of Adverse Events Leading to Study Drug Discontinuation
Table 14.3.3.2
Safety
Listing of Serious Adverse Events
Table 14.3.3.3
Safety
Listing of Deaths


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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13.1.3.4. Abnormal Laboratory Values
Table Number
Population
Table Title / Summary
NA
13.1.3.5. Laboratory Data Summary Tables
Table Number
Population
Table Title / Summary
Table 14.3.5.1.1.1
Safety
Cohort 1: Summary of Serum Chemistry Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.1.1.2
Safety
Cohort 2: Summary of Serum Chemistry Laboratory Results
(Standard Units) by Study Visit – Cohort 2
Table 14.3.5.1.2.1
Safety
Cohort 1: Shift from Baseline in Clinical Chemistry Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.1.2.2
Safety
Cohort 2: Shift from Baseline in Clinical Chemistry Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.2.1.1
Safety
Cohort 1: Summary of Hematology Laboratory Results (Standard Units)
by Study Visit
Table 14.3.5.2.1.2
Safety
Cohort 2: Summary of Hematology Laboratory Results (Standard Units)
by Study Visit
Table 14.3.5.2.2.1
Safety
Cohort 1: Shift from Baseline in Hematology Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.2.2.2
Safety
Cohort 2: Shift from Baseline in Hematology Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.3.1.1
Safety
Cohort 1: Summary of Quantitative Urinalysis Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.3.1.2
Safety
Cohort 2: Summary of Quantitative Urinalysis Laboratory Results
(Standard Units) by Study Visit
Table 14.3.5.3.2.1
Safety
Cohort 1: Shift from Baseline in Quantitative and Qualitative Urinalysis
Laboratory Results (Standard Units) by Study Visit
Table 14.3.5.3.2.2
Safety
Cohort 2: Shift from Baseline in Quantitative and Qualitative Urinalysis
Laboratory Results (Standard Units) by Study Visit
Table 14.3.5.3.3.1
Safety
Cohort 1: Summary of Qualitative Urinalysis Laboratory Results by
Study Visit
Table 14.3.5.3.3.2
Safety
Cohort 2: Summary of Qualitative Urinalysis Laboratory Results by
Study Visit


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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13.1.3.6. Other Safety Data Summary Tables
Table Number
Population
Table Title / Summary
Table 14.3.6.1.1
Safety
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment
(Dermal Response) by Study Visit
Table 14.3.6.1.2
Safety
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment
(Dermal Response) by Study Visit
Categorical Results
Table 14.3.6.1.3
Safety
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment
(Other Effects) by Study Visit
Categorical Results
Table 14.3.6.2.1
Safety
Cohorts 1 and 2: Summary of Subject Local Tolerability Assessment by
Study Visit
Table 14.3.6.2.2
Safety
Cohorts 1 and 2: Summary of Subject Local Tolerability Assessment by
Study Visit
Categorical Results
Table 14.3.6.3.1
Safety
Cohort 1: Summary of Vital Signs by Study Visit
Table 14.3.6.3.2
Safety
Cohort 2: Summary of Vital Signs by Study Visit
Table 14.3.6.4.1.1
Safety
Cohort 1: Summary of 12-Lead Electrocardiogram by Study Visit
Table 14.3.6.4.1.2
Safety
Cohort 2: Summary of 12-Lead Electrocardiogram by Study Visit
Table 14.3.6.4.2.1
Safety
Cohort 1: Summary of 12-Lead Electrocardiogram Interpretation by
Study Visit
Table 14.3.6.4.2.2
Safety
Cohort 2: Summary of 12-Lead Electrocardiogram Interpretation by
Study Visit
Table 14.3.6.5.1
Safety
Cohort 1: Summary of Physical Examination by Study Visit
Table 14.3.6.5.2
Safety
Cohort 2: Summary of Physical Examination by Study
Table 14.3.6.6
Safety
Cohorts 1 and 2: Summary of Concomitant Medications by ATC Class
Level 4 and Preferred Term


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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Date 09-Apr-2021
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AD-PR-109.02 Effective date: 17-Aug-2020
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13.1.4. Pharmacokinetic Data
13.1.4.1. Pharmacokinetic Data Summary Tables
Table 11:
Pharmacokinetic Data
Table Number
Population
Table Title / Summary
Table 14.4.1.1
PK
Cohort 1: Summary of Pharmacokinetic Results by Study Visit and
Time Point
Table 14.4.1.2
PK
Cohort 2: Summary of Pharmacokinetic Results by Study Visit and
Time Point
Table 14.4.2
PK
Cohort 1: Summary of Pharmacokinetic Parameters by Study Visit
13.2.
Planned Listing Descriptions
The following are planned data and patient/subject data listings for protocol number
ARQ-252-205.
In general, one listing will be produced per CRF domain. All listings will be sorted by treatment,
site, and subject number. All calculated variables will be included in the listings. Screen failures
will only be presented in Listing 16.2.2.1.
In all listings a blank line will be placed between each subject. Within a data listing, if an item
appears line after line (e.g., repetition of subject number), then only the first occurrence will be
displayed.
In data listings, the information for one subject will be kept on one page if at all possible, rather
than splitting a subject’s information across pages.
Table 12:
Planned Listings
16.2.1 Subject Discontinuations/Completions
Listing Number
Population
Title
Listing 16.2.1.1
All Subjects
Subject Disposition
Listing 16.2.1.2
All Subjects
Subject Visits
16.2.2 Protocol Deviations
Listing Number
Population
Title
Listing 16.2.2.1
All Subjects
Inclusion and Exclusion Criteria Not Met
Listing 16.2.2.2
All Subjects
Protocol Deviations


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
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16.2.3 Subjects Excluded from the Efficacy Analyses
Listing Number
Population
Title
Listing 16.2.3.1
All Subjects
Subject Randomization
Listing 16.2.3.2
All Subjects
Analysis Populations
16.2.4 Demographic Data and Other Baseline Characteristics
Listing Number
Population
Title
Listing 16.2.4.1.1
All Subjects
Subject Demographics
Listing 16.2.4.1.2
All Subjects
Baseline Characteristics
Listing 16.2.4.2.1
All Subjects
Medical History
Listing 16.2.4.2.2
All Subjects
Chronic Hand Eczema Medical History
16.2.5 Compliance and/or Drug Concentration Data
Listing Number
Population
Title
Listing 16.2.5.1
All Subjects
Study Drug Application at the Study Site
Listing 16.2.5.2
All Subjects
Study Drug Accountability
Listing 16.2.5.3
All Subjects
Diary Dispensation
Listing 16.2.5.4
All Subjects
Compliance (CRF)
Listing 16.2.5.5.1
All Subjects
Study Drug Interruption (QD)
Listing 16.2.5.5.2
All Subjects
Study Drug Interruption (BID)
Listing 16.2.5.6.1
PK
Cohort 1: Pharmacokinetic Sample Collection
Listing 16.2.5.6.2
PK
Cohort 2: Pharmacokinetic Sample Collection
Listing 16.2.5.7
PK
Cohort 1: Pharmacokinetic Calculated Parameters
16.2.6 Individual Efficacy Response Data
Listing Number
Population
Title
Listing 16.2.6.1
All Subjects
Investigator Global Assessment (IGA)
Listing 16.2.6.2
All Subjects
Worst Itch Numerical Rating Scale (WI-NRS)
Listing 16.2.6.3
All Subjects
Hand Eczema Severity Index (HECSI)
Listing 16.2.6.4
All Subjects
Pain Numeric Rating Scale (NRS)
Listing 16.2.6.5
All Subjects
Quality of Life in Hand Eczema Questionnaire (QOLHEQ)
Listing 16.2.6.6
All Subjects
Body Surface Area (BSA)
Listing 16.2.6.7
All Subjects
Nail Dystrophy Assessment


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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16.2.7 Adverse Event Listings (by Subject)
Listing Number
Population
Title
Listing 16.2.7.1
All Subjects
Adverse Events
16.2.8 Laboratory Values (by Subject)
Listing Number
Population
Title
Listing 16.2.8.1.1
All Subjects
Clinical Laboratory Data: Clinical Chemistry
Listing 16.2.8.1.2
All Subjects
Clinical Laboratory Data: Hematology
Listing 16.2.8.1.3
All Subjects
Clinical Laboratory Data: Urinalysis
Listing 16.2.8.1.4
All Subjects
Clinical Laboratory Data: TSH/T4
Listing 16.2.8.1.5
Female Subjects
Clinical Laboratory Data: Serum and Urine Pregnancy Test
Listing 16.2.8.1.6
Female Subjects
Follicle Stimulating Hormone Test
16.2.9 Other Clinical Observations and Measurements (by Subject)
Listing Number
Population
Title
Listing 16.2.9.1
All Subjects
Investigator Local Tolerability Assessments
Listing 16.2.9.2
All Subjects
Subject Local Tolerability Assessments
Listing 16.2.9.3
All Subjects
Vital Signs
Listing 16.2.9.4
All Subjects
12-Lead Electrocardiogram (ECG)
Listing 16.2.9.5
All Subjects
Physical Examination
Listing 16.2.9.6
All Subjects
Medical Photography
Listing 16.2.9.7
All Subjects
Prior and Concomitant Medications
Listing 16.2.9.8.1
All Subjects
Hand Washing/Hand Sanitizer Use (QD Dosing)
Listing 16.2.9.8.2
All Subjects
Hand Washing/Hand Sanitizer Use (BID Dosing)
Listing 16.2.9.9
All Subjects
Modified Total Lesion Symptom Score (mTLSS)
14.
TABLES, LISTINGS, AND LISTING SHELLS
14.1.
Standard Layout for all Tables, Listings, and Figures
The following standard layout will be applied to all Tables, Listings, and Figures (TLFs) in
support of this study. Note that programming notes may be added if appropriate after each TLF
shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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Figure 1:
Standardized Layout
Arcutis Biotherapeutics, Inc.
CONFIDENTIAL
Page xx of xx
Protocol ARQ-252-205
<Version>
<Table, Listing, Figure> xx.x.x
<Title of Table Listing or Figure>
<Study Population and if applicable subgroup Description>
____________________________________________________________________________________________________________
Body of Table, Listing or Figure
___________________________________________________________________________________________________________
<Abbreviations: XXX = xxxxx; YYY = yyyyy.>
<Note: If directly Applicable>
Footnote 1 <if applicable> Recommendation is to keep footnotes to a minimum
Footnote 2 <if applicable>
Footnote n <if applicable>
\\statsdrive.premier-research.com\stats$\Arcutis\ARQ-252\ARQ-252-205\Analysis\Tables\<version>\<pgm name>.sas
Executed on DDMONYYYY at hh:mm on data from DDMONYYYY using SAS Version 9.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
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14.2.
Planned Table Shells


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 63 of 219
Table 14.1.1
Cohorts 1 and 2: Summary of Subject Disposition
All Randomized Subjects
Cohort 1
Cohort 2
Status
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Study Populations:
ITT Population [1]
--
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Safety Population [2]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PP Population [3]
--
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PRU4 Population [4]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PNRS4 Population [5]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PNRS3 Population [6]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PNRS2 Population [7]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
ND Population [8]
--
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
PK Population [9]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
All Treated Population [10]
XX (XX.X%)
--
--
--
--
--
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; ITT = Intent-to-treat; ND = nail dystrophy; NRS = Numeric Rating Scale; PNRS2 = Subjects with Pain
NRS Score ≥2 at Baseline; PNRS3 = Subjects with Pain NRS Score ≥3 at Baseline; PNRS4 = Subjects with Pain NRS Score ≥4 at Baseline; PP = per protocol; PRU4 = Subjects with
WI-NRS Pruritus Score ≥4 at Baseline; QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects enrolled (Cohort 1) or randomized (Cohort 2) within planned treatment and overall*100.
[1] The ITT population includes all subjects randomized to Cohort 2.
[2] The Safety population includes all subjects who are enrolled (Cohort 1) or randomized (Cohort 2) and received at least 1 confirmed dose of investigational product.
[3] The PP population includes all subjects in the Safety population in Cohort 2, who were at least 80% compliant with study medication application, and showed no important deviations
from the study protocol that would affect the interpretation of efficacy.
[4] The PRU4 population is a subset of the ITT population and includes subjects with WI-NRS pruritus score ≥4 at baseline.
[5] The PNRS4 population is a subset of the ITT population and includes subjects with Pain NRS score ≥4 at baseline.
[6] The PNRS3 population is a subset of the ITT population and includes subjects with Pain NRS score ≥3 at baseline.
[7] The PNRS2 population is a subset of the ITT population and includes subjects with Pain NRS score ≥2 at baseline.
[8] The ND population is a subset of the ITT population and includes subjects with nail dystrophy at baseline.
[9] The PK population includes all subjects receiving the active drug with sufficient plasma concentrations of ARQ-254 to define a profile, as determined by the pharmacokineticist.
[10] The All Treated Population includes all subjects in the Safety population in Cohort 1.
Reference Listings: 16.2.1.1, 16.2.3.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 64 of 219
Table 14.1.1 (cont.)
Cohorts 1 and 2: Summary of Subject Disposition
All Randomized Subjects
Cohort 1
Cohort 2
Status
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Completed Study
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Ongoing in Study
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Prematurely Discontinued from Study
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Reason for Discontinuation:
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Withdrawal by Subject
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Sponsor’s Decision
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Physician Decision
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Non-Compliance
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Protocol Violation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Lost to Follow-up
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Adverse Event
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Death
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Pregnancy
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Other
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; ITT = Intent-to-treat; ND = nail dystrophy; NRS = Numeric Rating Scale; PNRS2 = Subjects with Pain NRS
Score ≥2 at Baseline; PNRS3 = Subjects with Pain NRS Score ≥3 at Baseline; PNRS4 = Subjects with Pain NRS Score ≥4 at Baseline; PP = per protocol; PRU4 = Subjects with WI-NRS
Pruritus Score ≥4 at Baseline; QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects enrolled (Cohort 1) or randomized (Cohort 2) within planned treatment and overall*100.
[1] The ITT population includes all subjects randomized to Cohort 2.
[2] The Safety population includes all subjects who are enrolled (Cohort 1) or randomized (Cohort 2) and received at least 1 confirmed dose of investigational product.
[3] The PP population includes all subjects in the Safety population in Cohort 2, who were at least 80% compliant with study medication application, and showed no important deviations
from the study protocol that would affect the interpretation of efficacy.
[4] The PRU4 population is a subset of the ITT population and includes subjects with WI-NRS pruritus score ≥4 at baseline.
[5] The PNRS4 population is a subset of the ITT population and includes subjects with Pain NRS score ≥4 at baseline.
[6] The PNRS3 population is a subset of the ITT population and includes subjects with Pain NRS score ≥3 at baseline.
[7] The PNRS2 population is a subset of the ITT population and includes subjects with Pain NRS score ≥2 at baseline.
[8] The ND population is a subset of the ITT population and includes subjects with nail dystrophy at baseline.
[9] The PK population includes all subjects receiving the active drug with sufficient plasma concentrations of ARQ-254 to define a profile, as determined by the pharmacokineticist.
[10] The All Treated Population includes all subjects in the Safety population in Cohort 1.
Reference Listings: 16.2.1.1, 16.2.3.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 65 of 219
Table 14.1.1 (cont.)
Cohorts 1 and 2: Summary of Subject Disposition
All Randomized Subjects
Cohort 1
Cohort 2
Status
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Prematurely Discontinued from Study Due to
COVID-19 Disruption
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Reason for Discontinuation:
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Withdrawal by Subject
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Sponsor’s Decision
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Physician Decision
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Non-Compliance
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Protocol Violation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Lost to Follow-up
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Adverse Event
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Death
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Pregnancy
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Other
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; ITT = Intent-to-treat; ND = nail dystrophy; NRS = Numeric Rating Scale; PNRS2 = Subjects with Pain NRS
Score ≥2 at Baseline; PNRS3 = Subjects with Pain NRS Score ≥3 at Baseline; PNRS4 = Subjects with Pain NRS Score ≥4 at Baseline; PP = per protocol; PRU4 = Subjects with WI-NRS
Pruritus Score ≥4 at Baseline; QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects enrolled (Cohort 1) or randomized (Cohort 2) within planned treatment and overall*100.
[1] The ITT population includes all subjects randomized to Cohort 2.
[2] The Safety population includes all subjects who are enrolled (Cohort 1) or randomized (Cohort 2) and received at least 1 confirmed dose of investigational product.
[3] The PP population includes all subjects in the Safety population in Cohort 2, who were at least 80% compliant with study medication application, and showed no important deviations
from the study protocol that would affect the interpretation of efficacy.
[4] The PRU4 population is a subset of the ITT population and includes subjects with WI-NRS pruritus score ≥4 at baseline.
[5] The PNRS4 population is a subset of the ITT population and includes subjects with Pain NRS score ≥4 at baseline.
[6] The PNRS3 population is a subset of the ITT population and includes subjects with Pain NRS score ≥3 at baseline.
[7] The PNRS2 population is a subset of the ITT population and includes subjects with Pain NRS score ≥2 at baseline.
[8] The ND population is a subset of the ITT population and includes subjects with nail dystrophy at baseline.
[9] The PK population includes all subjects receiving the active drug with sufficient plasma concentrations of ARQ-254 to define a profile, as determined by the pharmacokineticist.
[10] The All Treated Population includes all subjects in the Safety population in Cohort 1.
Reference Listings: 16.2.1.1, 16.2.3.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 66 of 219
Table 14.1.2.1
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Age (years)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Gender
Male
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Female
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Child-Bearing Potential? [1]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Ethnicity
Hispanic or Latino
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Hispanic or Latino
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety Population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 67 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Race
American-Indian or Alaska Native
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Asian
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Black or African-American
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Native Hawaiian or Other Pacific
Islander
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
White
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Other
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
More than One Race
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Height (cm)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Weight (kg)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Body Mass Index (kg/m2)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 68 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Body Surface Area (%) Affected by
Disease
Dorsal (Left Hand)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Dorsal (Right Hand)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Palmar (Left Hand)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Palmar (Right Hand)
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 69 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Body Surface Area (%) Affected by
Disease (cont.)
Total Hand
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline IGA
Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Almost Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Baseline IGA - Numeric
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 70 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline WI-NRS - Numeric [2]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline WI-NRS [2]
0
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
5
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
6
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
7
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
8
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
9
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
10
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 71 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline HECSI Fingertips Subscore (range 0-
72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Fingertips Subscore, where
subscore > 0 (range 1-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Fingers (Except Tips)
Subscore (range 0-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Fingers (Except Tips)
Subscore, where subscore > 0 (range 1-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 72 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline HECSI Palm of Hands Subscore
(range 0-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Palm of Hands Subscore,
where subscore > 0 (range 1-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Back of Hands Subscore
(range 0-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Back of Hands Subscore,
where subscore > 0 (range 1-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand Eczema
Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 73 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline HECSI Wrists Subscore (range 0-72)
[3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Wrists Subscore, where
subscore > 0 (range 1-72) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline HECSI Total Score (range 0-360) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline Pain NRS - Numeric [4]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 74 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline Pain NRS [4]
0
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
5
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
6
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
7
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
8
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
9
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
10
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Baseline QOLHEQ Symptoms Subscore
(range 0-27) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 75 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline QOLHEQ Emotions Subscore (range
0-31) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline QOLHEQ Functioning Subscore
(range 0-32) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Baseline QOLHEQ Treatment and Prevention
Subscore (range 0-27) [3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 76 of 219
Table 14.1.2.1 (cont.)
Cohorts 1 and 2: Summary of Demographics and Baseline Characteristics
Safety Population
Cohort 1
Cohort 2
Variable
Statistic or Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream
QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Overall
(N=XXX)
Baseline QOLHEQ Total Score (range 0-117)
[3]
n
XX
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Presence of Nail Dystrophy
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Nail with Worst Dystrophy
Left
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; NRS = numeric rating scale; QD = once daily; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the Safety population within overall (Cohort 1) or treatment received (Cohort 2)*100.
[1] Only captured for female subjects; percentages are based on the number of female subjects in the Safety population.
[2] The WI-NRS was determined by asking the subject’s assessment of worst itch over the past 24 hours. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[3] Lower scores indicate better outcomes.
[4] The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours. The scale is from 0 to 10, which ranges from “no pain” to “worst possible pain”.
Reference Listings: 16.2.4.1.1, 16.2.4.1.2, 16.2.6.1, 16.2.6.2, 16.2.6.3, 16.2.6.4, 16.2.6.5, 16.2.6.6, 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 77 of 219
Table 14.1.2.2
Cohort 2: Summary of Demographics and Baseline Characteristics
ITT Population
(Same shell as Table 14.1.2.1; only display Cohort 2 treatments; replace first footnote with “Note: Percentages are n/Number of subjects in the ITT population planned treatment *100.”)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 78 of 219
Table 14.1.3.1
Cohorts 1 and 2: Summary of Medical History by System Organ Class and Preferred Term
Safety Population
Cohort 1
Cohort 2
System Organ Class
Preferred Term
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 Recorded Medical
History
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; PT = preferred term; QD = once daily; SOC = system organ class.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received*100. Medical histories were coded using MedDRA version 23.0. Subjects were counted once
for each SOC and once for each PT. Medical history terms are displayed by descending frequency of SOC over all subjects, then PT within SOC, and then alphabetically by PT.
Reference Listing: 16.2.4.2.1, 16.2.4.2.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 79 of 219
Table 14.1.3.2
Cohorts 1 and 2: Summary of Chronic Hand Eczema Medical History
Safety Population
Cohort 1
Cohort 2
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Morphologic Subtype of Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Chronic Fissured Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Recurrent Vesicular Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Hyperkeratotic Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Pulpitis
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Interdigital Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Nummular Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Unclassified Hand Eczema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Patch Test Results [1]
Positive
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Negative
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Tested/Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Distribution of Chronic Hand Eczema
Palmar (including lateral aspects of fingers)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Left Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Dorsal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Left Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Interdigital
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Left Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Pulpitis
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Left Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right Hand
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received*100.
[1] Includes results from if the subject has ever been patched tested and results from the past 3 years. If a subject has results from both patch test questions, the worst case is presented here.
Reference Listings: 16.2.4.2.1, 16.2.4.2.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 80 of 219
Table 14.1.4
Cohorts 1 and 2: Summary of Protocol Deviations
Safety Population
Cohort 1
Cohort 2
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with Any Protocol Deviations
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with Any Protocol Deviations Related to
COVID-19 Disruption
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with Important Protocol Deviations
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received*100. Only important protocol deviations are presented. Subjects with Any Protocol
Deviations row can include counts from important and not important deviations. Subjects with one or more deviations within a type of protocol deviation were counted only once. Protocol
Deviations were collected throughout the study.
Reference Listing: 16.2.2.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 81 of 219
Table 14.1.5
Cohorts 1 and 2: Summary of Prior Medications by ATC Class Level 4 and Preferred Term
Safety Population
Cohort 1
Cohort 2
ATC Class Level 4
Preferred Term
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 Prior Medication
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
ATC Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
ATC Class 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: ATC = Anatomic Therapeutic Chemical; BID = twice daily; PT = preferred term; QD = once daily; WHO-DDE = World Health Organization-Drug Dictionary Enhanced.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. Medications were coded using WHO-DDE Global B3 version September 2019. Prior
medications are all medications that were started before the application of study drug. Medications are displayed by alphabetical order of ATC Level 4 classification, then descending
frequency of PT within ATC, and then alphabetically by PT. Subjects were counted only once for each ATC and PT.
[1] ATC Level 4 was not definable for these preferred terms due to multiple ingredients that cannot be mapped to an ATC Level 4 term, route of administration and indication that is not
defined in an ATC Level 4 term, or some similar circumstance.
Reference Listing: 16.2.9.7
Programming note: ATC & PT text should be presented as is from the dataset. If medications are coded but are missing ATC Class Level 4, display as “NOT DEFINED [1]” in the ATC Class Level 4
row and include footnote [1]; otherwise remove footnote [1] from the table.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 82 of 219
Table 14.1.6
Cohorts 1 and 2: Summary of Study Drug Exposure and Compliance
Safety Population
Cohort 1
Cohort 2
Variable
Statistic / Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Total Number of IP Applications
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Total Weight of IP Applied (g) [1]
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
XX.X (XX.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Compliance [2]
>100%
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
≥80% - ≤100%
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
< 80%
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
> 3 Consecutive Missed Days
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Compliant [3]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; IP = investigational product; QD = once daily.
Note: n is the number of subjects in the Safety Population. Percentages are n/Number of subjects in the Safety Population within treatment received*100.
[1] Total weight of IP is determined by subtracting returned tube weight from the dispensed tube weight.
[2] Compliance is calculated based on number of applications divided by the expected number of IP applications for each subject*100.
[3] A subject is considered compliant if the subject applies at least 80% of the expected applications during the IP application period and does not miss more than 3 consecutive days of
dosing (3 doses for QD and 6 doses for BID).
Reference Listings: 16.2.5.1, 16.2.5.2, 16.2.5.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 83 of 219
Table 14.2.1.1.1
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Multiple Imputation
Categorical Results
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Baseline
XX
XX
XX
XX
0 = Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4 = Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 2
XX
XX
XX
XX
0 = Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4 = Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
IGA Score of “Clear” or “Almost Clear” [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: The grades and success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation
steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at particular
visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For non-monotone missing IGA
values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into monotone before applying the predictive mean
matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream 0.3%
QD vs vehicle cream (all dose frequencies); ARQ-252 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream (all dose frequencies).


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 84 of 219
Reference Listing: 16.2.6.1
Table 14.2.1.1.2
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Multiple Imputation
Categorical Results
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Baseline
XX
XX
XX
0 = Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4 = Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 2
XX
XX
XX
0 = Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Mild
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Moderate
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4 = Severe
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
IGA Score of “Clear” or “Almost Clear” [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: The grades and success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation
steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at particular
visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For non-monotone missing IGA
values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into monotone before applying the predictive mean
matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
(all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 85 of 219
Table 14.2.1.2.1
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.1.1; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.2.2
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.1.2; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 86 of 219
Table 14.2.1.2.3
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
PP Population
(Same shell as Table 14.2.1.1.1; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.2.4
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Grades and Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
PP Population
(Same shell as Table 14.2.1.1.2; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 87 of 219
Table 14.2.1.2.5
Cohort 1: Summary of Investigator Global Assessment (IGA) Grades Score of “Clear” or “Almost Clear” by Study Visit – Observed Data
Categorical Results
All Treated Population
Study Visit
Category/Statistic
Cohort 1
ARQ-252 Cream 0.3% QD
(N=XX)
Baseline
XX
0 = Clear
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
2 = Mild
XX (XX.X%)
3 = Moderate
XX (XX.X%)
4 = Severe
XX (XX.X%)
Week 2
XX
0 = Clear
XX (XX.X%)
1 = Almost Clear
XX (XX.X%)
2 = Mild
XX (XX.X%)
3 = Moderate
XX (XX.X%)
4 = Severe
XX (XX.X%)
IGA Score of “Clear” or “Almost Clear” [1]
Yes
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
No
XX (XX.X%)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the All Treated population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or before the
day of first application of study drug.
[1] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 88 of 219
Table 14.2.1.3.1
Cohort 2: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Multiple Imputation
Categorical Results
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
XX
IGA Success [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation steps were
used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at particular visit
having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For non-monotone missing IGA
values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into monotone before applying the predictive mean
matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing
measurement taken on or before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 89 of 219
Table 14.2.1.3.2
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Multiple Imputation
Categorical Results
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
IGA Success [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple
imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value
for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent
variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data
pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned
treatment at each visit*100. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 90 of 219
Table 14.2.1.3.3
Cohort 2: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit and Baseline IGA Score – Multiple Imputation
Categorical Results
ITT Population
Baseline IGA Score = X
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
XX
IGA Success [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation steps
were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at particular
visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For non-monotone
missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into monotone before applying
the predictive mean matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at each visit and subgroup*100.
Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] IGA Success plus ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No”
otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group) comparing: ARQ-252 cream 0.3% QD vs vehicle
cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 91 of 219
Table 14.2.1.3.4
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit and Baseline IGA Score – Multiple Imputation
Categorical Results
ITT Population
Baseline IGA Score = X
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
IGA Success [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple
imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value
for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent
variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data
pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned
treatment at each visit and subgroup*100. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] IGA Success plus ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No”
otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group) comparing: ARQ-252 cream
(all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 92 of 219
Table 14.2.1.3.5
Cohort 2: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.3.1; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.3.6
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.3.2; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 93 of 219
Table 14.2.1.3.7
Cohort 2: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Observed Data
Categorical Results
PP Population
(Same shell as Table 14.2.1.3.1; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.3.8
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Observed Data
Categorical Results
PP Population
(Same shell as Table 14.2.1.3.2; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 94 of 219
Table 14.2.1.3.9
Cohort 2: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit and Baseline IGA Score – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.3.3; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NE = not estimable; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit and subgroup*100. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group) comparing: ARQ-252 cream 0.3% QD
vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.3.10
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit and Baseline IGA Score – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.3.4; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; NE = not estimable.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit and subgroup*100. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group) comparing: ARQ-252 cream
(all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 95 of 219
Table 14.2.1.3.11
Cohort 2: Summary of Proportion of Subjects Achieving Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
at Week 12 by Study Site – Observed Data
Categorical Results
ITT Population
Cohort 2
Study Site
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
SITENAME1 (Site SITEID1)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME2 (Site SITEID2)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME3 (Site SITEID3)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME4 (Site SITEID4)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME5 (Site SITEID5)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME6 (Site SITEID6)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
…
Abbreviations: BID = twice daily; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at Week 12 for each subgroup*100. Baseline is the last non-missing measurement taken on
or before the day of first application of study drug. IGA Success is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline.
Reference Listing: 16.2.6.1
Programming note: for the first column, use the site name (SITENAM variable) and site number (SITEID variable), e.g, “DermEffects (Site 103)”.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 96 of 219
Table 14.2.1.3.12
Cohort 2, Pooled Treatments: Summary of Proportion of Subjects Achieving Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear”
plus ≥2-point Improvement from Baseline) at Week 12 by Study Site – Observed Data
Categorical Results
ITT Population
Cohort 2
Study Site
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
SITENAME1 (Site SITEID1)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME2 (Site SITEID2)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME3 (Site SITEID3)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME4 (Site SITEID4)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME5 (Site SITEID5)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
SITENAME6 (Site SITEID6)
XX/XX (XX.X%)
XX/XX (XX.X%)
XX/XX (XX.X%)
…
Abbreviation: IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at Week 12 for each subgroup*100. Baseline is the last non-missing
measurement taken on or before the day of first application of study drug. IGA Success is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade
improvement from baseline
Reference Listing: 16.2.6.1
Programming note: for the first column, use the site name (SITENAM variable) and site number (SITEID variable), e.g, “DermEffects (Site 103)”.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 97 of 219
Table 14.2.1.3.13
Cohort 1: Summary of Investigator Global Assessment (IGA) Success (Score of “Clear” or “Almost Clear” plus ≥2-point Improvement from Baseline)
by Study Visit – Observed Data
Categorical Results
All Treated Population
Study Visit
Category/Statistic
Cohort 1
ARQ-252 Cream 0.3% QD
(N=XX)
Week 2
XX
IGA Success [1]
Yes
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
No
XX (XX.X%)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the All Treated population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or before the
day of first application of study drug.
[1] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 98 of 219
Table 14.2.1.4.1
Cohort 2: Summary of Investigator Global Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit – Multiple Imputation
Categorical Results
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
XX
IGA ≥2-point Improvement from Baseline [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation steps
were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at particular
visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For non-monotone
missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into monotone before applying the
predictive mean matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-
missing measurement taken on or before the day of first application of study drug.
[1] IGA ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score with a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 99 of 219
Table 14.2.1.4.2
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit – Multiple Imputation
Categorical Results
ITT Population
(Same shell as Table 14.2.1.3.2 but using the same first column as Table 14.2.1.4.1; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: The success scores were summarized using observed dataset. The odds ratio and P values were summarized using multiple imputation dataset. Separate multiple imputation
steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute missing value for a subject at
particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as dependent variable. For
non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data pattern into
monotone before applying the predictive mean matching multiple imputation algorithm. Percentages are n/Number of subjects in the ITT population within planned treatment at
each visit*100. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] IGA ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score with a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252
cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.4.3
Cohort 2: Summary of Investigator Global Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.4.1; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score with a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 100 of 219
Table 14.2.1.4.4
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit – Observed Data
Categorical Results
ITT Population
(Same shell as Table 14.2.1.4.2; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score with a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.1
Table 14.2.1.4.5
Cohort 1: Summary of Investigator Global Assessment (IGA) ≥2-point Improvement from Baseline by Study Visit – Observed Data
Categorical Results
All Treated Population
(Same shell as Table 14.2.1.3.13 but using the same first column as Table 14.2.1.4.1; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the All Treated population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
[1] IGA ≥2-point Improvement from Baseline (“Yes”) is defined as an IGA score with a ≥2-grade improvement from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 101 of 219
Table 14.2.1.5.1
Cohort 2: Summary and Change from Baseline in Investigator Global Assessment (IGA) Grades by Study Visit – Multiple Imputation
ITT Population
Cohort 2
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
Statistic
Observed
Change
Observed
Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
Week 4
n
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drugs (ARQ-252 Cream 0.1% QD, Vehicle Cream (All Dose Frequencies)), showing the same study visits shown here. Then continue
for Weeks 8, 12, and 13.
Abbreviations: BID = twice daily; IGA = investigator global assessment; QD = once daily; SD = standard deviation.
Note: Separate multiple imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to
impute missing value for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study
visit as dependent variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the
missing data pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Subjects are summarized by averaging results over all imputed
datasets within a subject before summarizing by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity involving an ordinal scale with
5 severity grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe. Baseline is the last non-missing measurement taken
on or before the day of first application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 102 of 219
Table 14.2.1.5.2
Cohort 2, Pooled Treatments: Summary and Change from Baseline in Investigator Global Assessment (IGA) Grades by Study Visit – Multiple Imputation
ITT Population
Cohort 2
Study Visit
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Statistic
Observed
Change
Observed
Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
Week 4
n
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drug (Vehicle Cream (All Dose Frequencies)), showing the same study visits shown here. Then continue for Weeks 8, 12,
and 13.
Abbreviations: IGA = investigator global assessment; SD = standard deviation.
Note: Separate multiple imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model
was used to impute missing value for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent
variables and outcome at study visit as dependent variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute
the data at intermediate visits to make the missing data pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Subjects are
summarized by averaging results over all imputed datasets within a subject before summarizing by planned treatment. IGA is a static qualitative evaluation of overall
chronic hand eczema severity involving an ordinal scale with 5 severity grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild;
3 = Moderate; 4 = Severe. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is calculated
as result – baseline result.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 103 of 219
Table 14.2.1.5.3
Cohort 2: Summary and Change from Baseline in Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data
ITT Population
(Same shell as Table 14.2.1.5.1; use the below footnotes)
Abbreviations: BID = twice daily; IGA = investigator global assessment; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity involving an ordinal scale with 5 severity
grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.6.1
Table 14.2.1.5.4
Cohort 2, Pooled Treatments: Summary and Change from Baseline in Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data
ITT Population
(Same shell as Table 14.2.1.5.2; use the below footnotes)
Abbreviations: IGA = investigator global assessment; SD = standard deviation.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity involving an ordinal scale with 5 severity
grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 104 of 219
Table 14.2.1.5.5
Cohort 1: Summary and Change from Baseline in Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data
All Treated Population
Cohort 1
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
Statistic
Observed
Change
Baseline
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Q1, Q3
XX.X
Week 2
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Abbreviations: IGA = investigator global assessment; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand
eczema severity involving an ordinal scale with 5 severity grades (reported only in integers of 0 to 4) where
0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe. Baseline is the last non-missing measurement taken
on or before the day of first application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 105 of 219
Table 14.2.1.6.1
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades by Study Visit – Multiple Imputation – ANCOVA
ITT Population
Cohort 2
Study Visit
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
Change from Baseline
n
XX
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for Difference from Vehicle)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for Difference from Vehicle)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily; SE = standard
error.
Note: Separate multiple imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to impute
missing value for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit as
dependent variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data
pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of
overall chronic hand eczema severity involving an ordinal scale with 5 severity grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate;
4 = Severe.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site
group, and baseline IGA grade as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies]; or
ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 106 of 219
Table 14.2.1.6.2
Cohort 2, Pooled Treatments: Summary of Investigator Global Assessment (IGA) Grades by Study Visit – Multiple Imputation – ANCOVA
ITT Population
Cohort 2
Study Visit
Category
Statistic [1]
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
Change from Baseline
n
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for Difference from Vehicle)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for Difference from Vehicle)
(X.XX, X.XX)
(X.XX, X.XX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13.
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; SE = standard error.
Note: Separate multiple imputation steps were used for monotone and non-monotone missing data. For monotone missing pattern, a predictive mean matching model was used to
impute missing value for a subject at particular visit having IGA score at previous study visit, treatment group, and pooled site group as independent variables and outcome at study visit
as dependent variable. For non-monotone missing IGA values, Markov-Chain Monte Carlo (MCMC) method was used to impute the data at intermediate visits to make the missing data
pattern into monotone before applying the predictive mean matching multiple imputation algorithm. Subjects are summarized by planned treatment. IGA is a static qualitative
evaluation of overall chronic hand eczema severity involving an ordinal scale with 5 severity grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild;
3 = Moderate; 4 = Severe.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site
group, and baseline IGA grade as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies] minus
vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 107 of 219
Table 14.2.1.6.3
Cohort 2: Summary of Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data – ANCOVA
ITT Population
(Same shell as Table 14.2.1.6.1; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily;
SE = standard error.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity involving an ordinal scale with 5 severity
grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, and baseline IGA grade as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.1
Table 14.2.1.6.4
Cohort 2, Pooled Treatment: Summary of Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data – ANCOVA
ITT Population
(Same shell as Table 14.2.1.6.2; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; SE = standard error.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity involving an ordinal scale with 5 severity
grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild; 3 = Moderate; 4 = Severe.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, and baseline IGA grade as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 108 of 219
Table 14.2.1.6.5
Cohort 1: Summary of Investigator Global Assessment (IGA) Grades by Study Visit – Observed Data – ANCOVA
All Treated Population
Study Visit
Cohort 1
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
Week 2
Change from Baseline
n
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-
squares; QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. IGA is a static qualitative evaluation of overall chronic hand eczema severity
involving an ordinal scale with 5 severity grades (reported only in integers of 0 to 4) where 0 = Clear; 1 = Almost Clear; 2 = Mild;
3 = Moderate; 4 = Severe.
[1] Estimates for LS means (change from baseline), accompanying 90% and 95% CIs, and P values are from an ANCOVA with
treatment group, pooled site group, and baseline IGA grade as independent variables. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
Reference Listing: 16.2.6.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 109 of 219
Table 14.2.2.1.1
Cohort 2: Summary and Change and Percent Change from Baseline in Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week
ITT Population
Cohort 2
Study Week
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
Statistic
Observed
Change
% Change
Observed
Change
% Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 1
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drugs (ARQ-252 Cream 0.1% QD, and Vehicle Cream (All Dose Frequencies)), showing the same study visits shown
here. Then continue for Weeks 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: BID = twice daily; QD = once daily; SD = standard deviation; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by planned treatment. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past
24 hours; average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study
week. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”. Baseline is the last non-missing measurement taken before the day of first
application of study drug. Change from baseline is calculated as result – baseline result. Percent change from baseline is calculated as (change from
baseline/baseline)*100.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 110 of 219
Table 14.2.2.1.2
Cohort 2, Pooled Treatments: Summary and Change and Percent Change from Baseline in Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score
by Study Week
ITT Population
Cohort 2
Study Week
ARQ-252 Cream (All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3% (All Dose Frequencies)
(N=XX)
Statistic
Observed
Change
% Change
Observed
Change
% Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 1
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drug (Vehicle Cream (All Dose Frequencies)), showing the same study visits shown here. Then continue for Weeks 4, 5,
6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: SD = standard deviation; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by planned treatment. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past
24 hours; average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study
week. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”. Baseline is the last non-missing measurement taken before the day of first
application of study drug. Change from baseline is calculated as result – baseline result. Percent change from baseline is calculated as (change from
baseline/baseline)*100.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 111 of 219
Table 14.2.2.1.3
Cohort 2: Summary of Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week – ANCOVA
ITT Population
Cohort 2
Study Week
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 1
Change from Baseline
n
XX
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
X.XXXX
Percent Change from Baseline
n
XX
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily; SE = standard error;
WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by planned treatment. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past 24 hours; average weekly
WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from 0 to 10, which ranges from
“no itch” to “worst imaginable itch”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site group,
baseline IGA grade, and baseline WI-NRS pruritus score as independent variables. Baseline is the last non-missing measurement taken before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies]; or ARQ-252
cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 112 of 219
Table 14.2.2.1.4
Cohort 2, Pooled Treatments: Summary of Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week – ANCOVA
ITT Population
Cohort 2
Study Week
Category
Statistic [1]
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 1
Change from Baseline
n
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
Percent Change from Baseline
n
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
Continue for Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily;
SE = standard error; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by planned treatment. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past 24 hours;
average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from
0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline WI-NRS pruritus score as independent variables. Baseline is the last non-missing measurement taken before the day of first
application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 113 of 219
Table 14.2.2.1.5
Cohort 2: Summary of Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week – ANCOVA
PP Population
(Same shell as Table 14.2.2.1.3; visits include Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11, Week 12, and Week 13;
use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily;
SE = standard error; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by treatment received. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past 24 hours;
average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from
0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline WI-NRS pruritus score as independent variables. Baseline is the last non-missing measurement taken before the day of first
application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.2
Table 14.2.2.1.6
Cohort 2, Pooled Treatments: Summary of Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week – ANCOVA
PP Population
(Same shell as Table 14.2.2.2.4; visits include Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11, Week 12, and Week 13;
use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; SE = standard error; WI-NRS = Worst
Itch – Numeric Rating Scale.
Note: Subjects are summarized by treatment received. The WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past 24 hours;
average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from
0 to 10, which ranges from “no itch” to “worst imaginable itch”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline WI-NRS pruritus score as independent variables. Baseline is the last non-missing measurement taken before the day of first
application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 114 of 219
Table 14.2.2.1.7
Cohort 2: Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score Success (≥4-point Reduction from Baseline) by Study Week
ITT Population, Subjects with WI-NRS Pruritus Score ≥4 at Baseline (PRU4 Population)
Cohort 2
Study Week
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 1
XX
XX
XX
XX
WI-NRS ≥4-point Reduction from Baseline [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the PRU4 population within planned treatment at each visit*100. The WI-NRS pruritus score was determined by asking the subject’s
assessment of worst itch over the past 24 hours; average weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary
scores for each study week. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”. Baseline is the last non-missing measurement taken before the day of
first application of study drug.
[1] WI-NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly WI-NRS pruritus score with a ≥4-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252
cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 115 of 219
Table 14.2.2.1.8
Cohort 2, Pooled Treatments: Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score Success (≥4-point Reduction from Baseline) by Study Week
ITT Population, Subjects with WI-NRS Pruritus Score ≥4 at Baseline (PRU4 Population)
Cohort 2
Study Week
Category/Statistic
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 1
XX
XX
XX
WI-NRS ≥4-point Reduction from Baseline [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Continue for Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Abbreviations: CI = confidence interval; IGA = investigator global assessment; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the PRU4 population within planned treatment at each visit*100. The WI-NRS pruritus score was determined by
asking the subject’s assessment of worst itch over the past 24 hours; average weekly WI-NRS pruritus scores were calculated as the average of the reported
(non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] WI-NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly WI-NRS pruritus score with a ≥4-point reduction from baseline; “No”
otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade)
comparing: ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle
cream (all dose frequencies).
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 116 of 219
Table 14.2.2.1.9
Cohort 1: Summary and Change and Percent Change from Baseline in Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week
All Treated Population
Cohort 1
Study Week
ARQ-252 Cream 0.3% QD
(N=XX)
Statistic
Observed
Change
% Change
Baseline
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Q1, Q3
XX.X
Week 1
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
Repeat for Week 2.
Abbreviations: QD = once daily; SD = standard deviation; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by treatment received. The WI-NRS pruritus score was determined by asking the
subject’s assessment of worst itch over the past 24 hours; average weekly WI-NRS pruritus scores were calculated as
the average of the reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from
0 to 10, which ranges from “no itch” to “worst imaginable itch”. Baseline is the last non-missing measurement taken
before the day of first application of study drug. Change from baseline is calculated as result – baseline result. Percent
change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 117 of 219
Table 14.2.2.1.10
Cohort 1: Summary of Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score by Study Week – ANCOVA
All Treated Population
Study Week
Cohort 1
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
Week 1
Change from Baseline
n
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
Percent Change from Baseline
n
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
Repeat for Week 2.
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment;
LS = least-squares; QD = once daily; SE = standard error; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Subjects are summarized by treatment received. The WI-NRS pruritus score was determined by asking the subject’s
assessment of worst itch over the past 24 hours; average weekly WI-NRS pruritus scores were calculated as the average of the
reported (non-missing) WI-NRS pruritus daily diary scores for each study week. The scale is from 0 to 10, which ranges from
“no itch” to “worst imaginable itch”.
[1] Estimates for LS means (change from baseline), accompanying 90% and 95% CIs, and P values are from an ANCOVA
with treatment group, pooled site group, baseline IGA grade, and baseline WI-NRS pruritus score as independent variables.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 118 of 219
Table 14.2.2.1.11
Cohort 1: Average Weekly Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score Success (≥4-point Reduction from Baseline) by Study Week
All Treated Population, Subjects with WI-NRS Pruritus Score ≥4 at Baseline (PRU4 Population)
Cohort 1
Study Week
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
Week 1
XX
WI-NRS ≥4-point Reduction from Baseline [1]
Yes
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
No
XX (XX.X%)
Week 2
XX
WI-NRS ≥4-point Reduction from Baseline [1]
Yes
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
No
XX (XX.X%)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; QD = once daily; WI-NRS = Worst Itch –
Numeric Rating Scale.
Note: Percentages are n/Number of subjects in the PRU4 population within treatment received at each visit*100. The
WI-NRS pruritus score was determined by asking the subject’s assessment of worst itch over the past 24 hours; average
weekly WI-NRS pruritus scores were calculated as the average of the reported (non-missing) WI-NRS pruritus daily diary
scores for each study week. The scale is from 0 to 10, which ranges from “no itch” to “worst imaginable itch”. Baseline is
the last non-missing measurement taken before the day of first application of study drug.
[1] WI-NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly WI-NRS pruritus score with a
≥4-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 119 of 219
Table 14.2.2.2.1
Cohort 2: Summary and Change and Percent Change from Baseline in Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit
ITT Population
Parameter: Fingertips Subscore
Cohort 2
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
Statistic
Observed
Change
% Change
Observed
Change
% Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Week 4
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drugs (ARQ-252 Cream 0.1% QD, and Vehicle Cream (All Dose Frequencies)), showing the same study visits shown
here. Then continue for Weeks 8, 12, and 13. Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of
Hands Subscore, Wrists Subscore, and Total Score.
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the
extent of the lesions on each of 5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower
scores indicate better outcomes. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is
calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 120 of 219
Table 14.2.2.2.2
Cohort 2, Pooled Treatments: Summary and Change and Percent Change from Baseline in Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit
ITT Population
Parameter: Fingertips Subscore
Cohort 2
Study Visit
ARQ-252 Cream (All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream (All Dose Frequencies)
(N=XX)
Statistic
Observed
Change
% Change
Observed
Change
% Change
Baseline
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
Week 2
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Week 4
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drug (Vehicle Cream (All Dose Frequencies)), showing the same study visits shown here. Then continue for Weeks 8,
12, and 13. Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of Hands Subscore, Wrists Subscore,
and Total Score.
Abbreviations: BID = twice daily; HECSI = Hand Eczema Severity Index; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the
extent of the lesions on each of 5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower
scores indicate better outcomes. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is
calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 121 of 219
Table 14.2.2.2.3
Cohort 2: Summary of Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit – ANCOVA
ITT Population
Parameter: Fingertips Subscore
Cohort 2
Study Visit
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
Change from Baseline
n
XX
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
X.XXXX
Percent Change from Baseline
n
XX
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13. Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of Hands Subscore, Wrists Subscore, and Total
Score.
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; LS = least-squares;
QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of
5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site group, baseline
IGA grade, and baseline HECSI subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study
drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies]; or ARQ-252 cream 0.1%
QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 122 of 219


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 123 of 219
Table 14.2.2.2.4
Cohort 2, Pooled Treatments: Summary of Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit – ANCOVA
ITT Population
Parameter: Fingertips Subscore
Cohort 2
Study Visit
Category
Statistic [1]
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
Change from Baseline
n
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
Percent Change from Baseline
n
XX
XX
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
X.XX (X.XXX)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
X.XXXX
X.XXXX
LS Mean Difference from Vehicle (SE)
(X.XX, X.XX)
(X.XX, X.XX)
(90% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
(95% CI for Difference from Vehicle)
X.XX (X.XXX)
X.XX (X.XXX)
P value for Difference from Vehicle [3]
X.XXXX
X.XXXX
Continue for Weeks 4, 8, 12, and 13. Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of Hands Subscore,
Wrists Subscore, and Total Score.
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; LS = least-squares;
SE = standard error.
Note: Subjects are summarized by planned treatment. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of
the lesions on each of 5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better
outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline HECSI subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement taken
on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.3
Table 14.2.2.2.5


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 124 of 219
Cohort 2: Summary of Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit – ANCOVA
PP Population
(Same shell as Table 14.2.2.2.3; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment;
LS = least-squares; QD = once daily; SE = standard error.
Note: Subjects are summarized by treatment received. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of
the lesions on each of 5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better
outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline HECSI subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement taken
on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.3
Table 14.2.2.2.6
Cohort 2, Pooled Treatments: Summary of Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit – ANCOVA
PP Population
(Same shell as Table 14.2.2.2.4; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment;
LS = least-squares; QD = once daily; SE = standard error.
Note: Subjects are summarized by treatment received. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of
the lesions on each of 5 hand areas by use of standard scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better
outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline HECSI subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement taken
on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 125 of 219
Table 14.2.2.2.7
Cohort 2: Summary of Achievement of HECSI-75 by Study Visit
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
XX
HECSI-75 [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Week 4
XX
XX
XX
XX
HECSI-75 [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
X.XXXX
Continue for Weeks 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or before the first
application of study drug.
[1] HECSI-75 is populated with “Yes” when there is an achievement of a 75% reduction in HECSI total score from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream 0.3%
QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 126 of 219
Table 14.2.2.2.8
Cohort 2, Pooled Treatments: Summary of Achievement of HECSI-75 by Study Visit
ITT Population
Cohort 2
Study Visit
Category/Statistic
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Week 2
XX
XX
XX
HECSI-75 [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Week 4
XX
XX
XX
HECSI-75 [1]
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
90% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
95% CI [2]
(X.XX, X.XX)
(X.XX, X.XX)
(X.XX, X.XX)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Odds Ratio (90% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
Odds Ratio (95% CI) [3]
X.XX (X.XX, X.XX)
X.XX (X.XX, X.XX)
P value [3]
X.XXXX
X.XXXX
Continue for Weeks 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; QD = once daily.
Note: Percentages are n/Number of subjects in the ITT population within planned treatment at each visit*100. Baseline is the last non-missing measurement taken on or before the first application
of study drug.
[1] HECSI-75 is populated with “Yes” when there is an achievement of a 75% reduction in HECSI total score from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
(all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 127 of 219
Table 14.2.2.2.9
Cohort 2: Summary of Achievement of HECSI-75 by Study Visit
PP Population
(Same shell as Table 14.2.2.2.7; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; QD = once daily.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or before the first
application of study drug.
[1] HECSI-75 is populated with “Yes” when there is an achievement of a 75% reduction in HECSI total score from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.3
Table 14.2.2.2.10
Cohort 2, Pooled Treatments: Summary of Achievement of HECSI-75 by Study Visit
PP Population
(Same shell as Table 14.2.2.2.8; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; HECSI = Hand Eczema Severity Index; QD = once daily.
Note: Percentages are n/Number of subjects in the PP population within treatment received at each visit*100. Baseline is the last non-missing measurement taken on or before the first
application of study drug.
[1] HECSI-75 is populated with “Yes” when there is an achievement of a 75% reduction in HECSI total score from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing: ARQ-252 cream
(all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 128 of 219
Table 14.2.2.2.11
Cohort 1: Summary and Change and Percent Change from Baseline in Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit
All Treated Population
Parameter: Fingertips Subscore
Cohort 1
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
Statistic
Observed
Change
% Change
Baseline
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Q1, Q3
XX.X
Week 2
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of
Hands Subscore, Wrists Subscore, and Total Score.
Abbreviations: HECSI = Hand Eczema Severity Index; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. The HECSI is an instrument used in clinical trials to rate the
severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard
scales. The range for each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better
outcomes. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
Change from baseline is calculated as result – baseline result. Percent change from baseline is calculated as
(change from baseline/baseline)*100.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 129 of 219
Table 14.2.2.2.12
Cohort 1: Summary of Hand Eczema Severity Index (HECSI) Subscores and Total Score by Study Visit – ANCOVA
All Treated Population
Parameter: Fingertips Subscore
Study Visit
Cohort 1
Category
Statistic [1]
ARQ-252 Cream 0.3% QD
(N=XX)
Week 2
Change from Baseline
n
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
Percent Change from Baseline
n
XX
LS Mean Change from Baseline (SE)
X.XX (X.XXX)
(90% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
(95% CI for LS Mean Change from Baseline)
(X.XX, X.XX)
P value for LS Mean Change from Baseline [2]
X.XXXX
Repeat everything for the following parameters: Fingers (except Tips) Subscore, Palm of Hands Subscore, Back of Hands
Subscore, Wrists Subscore, and Total Score.
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; HECSI = Hand Eczema Severity Index;
IGA = investigator global assessment; LS = least-squares; QD = once daily; SE = standard error.
Note: Subjects are summarized by treatment received. The HECSI is an instrument used in clinical trials to rate the severity of
6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The range for
each subscore is 0 to 72, and the range for the total score is 0 to 360. Lower scores indicate better outcomes.
[1] Estimates for LS means (change from baseline), accompanying 90% and 95% CIs, and P values are from an ANCOVA
with treatment group, pooled site group, baseline IGA grade, and baseline HECSI subscore or total score (as appropriate) as
independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study
drug.
[2] P value for testing change from baseline is zero.
Reference Listing: 16.2.6.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 130 of 219
Table 14.2.2.3.1
Cohort 2: Summary and Change and Percent Change from Baseline in Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week
ITT Population
(Same shell as Table 14.2.2.1.1; use the below footnotes)
Abbreviations: BID = twice daily; NRS = Numeric Rating Scale; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS
scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from
0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement taken before the day of first application of study drug. Change from baseline is
calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.4
Table 14.2.2.3.2
Cohort 2, Pooled Treatments: Summary and Change and Percent Change from Baseline in Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week
ITT Population
(Same shell as Table 14.2.2.1.2; use the below footnotes)
Abbreviations: NRS = Numeric Rating Scale; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS
scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from
0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement taken before the day of first application of study drug. Change from baseline is
calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 131 of 219
Table 14.2.2.3.3
Cohort 2: Summary of Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week – ANCOVA
ITT Population
(Same shell as Table 14.2.2.1.3; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; NRS = Numeric
Rating Scale; QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores
were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from 0 = “no pain” and
10 = “worst possible pain”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline Pain NRS score as independent variables. Baseline is the last non-missing measurement taken before the day of first
application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.4
Table 14.2.2.3.4
Cohort 2, Pooled Treatments: Summary of Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week – ANCOVA
ITT Population
(Same shell as Table 14.2.2.1.4; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; NRS = Numeric
Rating Scale; QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores
were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from 0 = “no pain” and
10 = “worst possible pain”.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline Pain NRS score as independent variables. Baseline is the last non-missing measurement taken before the day of first
application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 132 of 219
Table 14.2.2.3.5
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥4-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥4 at Baseline (PNRS4 Population)
(Same shell as Table 14.2.2.1.7; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS4 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥4-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.4
Table 14.2.2.3.6
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥4-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥4 at Baseline (PNRS4 Population)
(Same shell as Table 14.2.2.1.8; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS4 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥4-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 133 of 219
Table 14.2.2.3.7
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥3-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥3 at Baseline (PNRS3 Population)
(Same shell as Table 14.2.2.1.7; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS3 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥3-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥3-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.4
Table 14.2.2.3.8
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥3-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥3 at Baseline (PNRS3 Population)
(Same shell as Table 14.2.2.1.8; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS3 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥3-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥3-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 134 of 219
Table 14.2.2.3.9
Cohort 2: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥2-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥2 at Baseline (PNRS2 Population)
(Same shell as Table 14.2.2.1.7; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS2 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥2-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥2-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream 0.3% QD vs vehicle cream (all dose frequencies); ARQ-252 cream 0.3% BID vs vehicle cream (all dose frequencies); and ARQ-252 cream 0.1% QD vs
vehicle cream (all dose frequencies).
Reference Listing: 16.2.6.4
Table 14.2.2.3.10
Cohort 2, Pooled Treatments: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥2-point Reduction from Baseline) by Study Week
ITT Population, Subjects with Pain NRS Score ≥2 at Baseline (PNRS2 Population)
(Same shell as Table 14.2.2.1.8; change instances of “WI-NRS” in table to “Pain NRS”; use the below footnotes)
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS2 population within planned treatment at each visit*100. The Pain NRS is the subject’s assessment of worst pain
intensity over the past 24 hours; average weekly Pain NRS scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study
week. The scale is from 0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”.
Baseline is the last non-missing measurement taken before the day of first application of study drug.
[1] Pain NRS ≥2-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥2-point reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
[3] The odds ratio, 90% and 95% CIs, and P value are obtained from Cochran Mantel Haenszel test (stratified by pooled site group and baseline IGA grade) comparing:
ARQ-252 cream (all strengths/dose frequencies) vs vehicle cream (all dose frequencies) and ARQ-252 cream 0.3% (all dose frequencies) vs vehicle cream
(all dose frequencies).
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 135 of 219
Table 14.2.2.3.11
Cohort 1: Summary and Change and Percent Change from Baseline in Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week
All Treated Population
(Same shell as Table 14.2.2.1.9; visits include Baseline, Week 1, and Week 2; use the below footnotes)
Abbreviations: NRS = Numeric Rating Scale; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS
scores were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from
0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement taken before the day of first application of study drug. Change from baseline is
calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.4
Table 14.2.2.3.12
Cohort 1: Summary of Average Weekly Pain Numeric Rating Scale (NRS) Score by Study Week – ANCOVA
All Treated Population
(Same shell as Table 14.2.2.1.10; visits include Baseline, Week 1, and Week 2; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; NRS = Numeric Rating Scale;
QD = once daily; SE = standard error.
Note: Subjects are summarized by treatment received. The Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores
were calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from 0 to 10, which ranges from 0 = “no pain” and
10 = “worst possible pain”.
[1] Estimates for LS means (change from baseline), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site group, baseline IGA
grade, and baseline Pain NRS score as independent variables. Baseline is the last non-missing measurement taken before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 136 of 219
Table 14.2.2.3.13
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥4-point Reduction from Baseline) by Study Week
All Treated Population, Subjects with Pain NRS Score ≥4 at Baseline (PNRS4 Population)
(Same shell as Table 14.2.2.1.11; visits include Baseline, Week 1, and Week 2; replace instances of WI-NRS with Pain NRS; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once
daily.
Note: Percentages are n/Number of subjects in the PNRS4 population within treatment received at each visit*100. The
Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores were
calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from
0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement
taken before the day of first application of study drug.
[1] Pain NRS ≥4-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥4-point
reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.4
Table 14.2.2.3.14
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥3-point Reduction from Baseline) by Study Week
All Treated Population, Subjects with Pain NRS Score ≥3 at Baseline (PNRS3 Population)
(Same shell as Table 14.2.2.1.11; visits include Baseline, Week 1, and Week 2; replace instances of WI-NRS with Pain NRS; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale; QD = once
daily.
Note: Percentages are n/Number of subjects in the PNRS3 population within treatment received at each visit*100. The
Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores were
calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from
0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement
taken before the day of first application of study drug.
[1] Pain NRS ≥3-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥3-point
reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 137 of 219
Table 14.2.2.3.15
Cohort 1: Average Weekly Pain Numeric Rating Scale (NRS) Score Success (≥2-point Reduction from Baseline) by Study Week
All Treated Population, Subjects with Pain NRS Score ≥2 at Baseline (PNRS2 Population)
(Same shell as Table 14.2.2.1.11; visits include Baseline, Week 1, and Week 2; replace instances of WI-NRS with Pain NRS; use the below footnotes)
Abbreviations: CI = confidence interval; IGA = investigator global assessment; NRS = Numeric Rating Scale;
QD = once daily.
Note: Percentages are n/Number of subjects in the PNRS2 population within treatment received at each visit*100. The
Pain NRS is the subject’s assessment of worst pain intensity over the past 24 hours; average weekly Pain NRS scores were
calculated as the average of the reported (non-missing) Pain NRS daily diary scores for each study week. The scale is from
0 to 10, which ranges from 0 = “no pain” and 10 = “worst possible pain”. Baseline is the last non-missing measurement
taken before the day of first application of study drug.
[1] Pain NRS ≥2-point Reduction from Baseline (“Yes”) is defined as an average weekly Pain NRS score with a ≥2-point
reduction from baseline; “No” otherwise.
[2] 90% and 95% CIs for “Yes” are obtained using Wilson method.
Reference Listing: 16.2.6.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 138 of 219
Table 14.2.2.4.1
Cohort 2: Summary and Change and Percent Change from Baseline in Quality of Life in Hand Eczema Questionnaire (QOLHEQ) Subscores and Total Score by Study Visit
ITT Population
(Same shell as Table 14.2.2.2.1; parameters include the following: Symptoms Subscore, Emotions Subscore, Limitations in Functioning Subscore, Treatment and Prevention Subscore, and
Total Score; use the below footnotes)
Abbreviations: BID = twice daily; QD = once daily; QOLHEQ = Quality of Life in Hand Eczema Questionnaire; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The construct Health Related Quality of Life (HRQOL) includes all impairments or limiting conditions caused by the
health state of an individual. The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. It consists of 30 items which can be
summarized according to these four domains: Impairments because of (1) symptoms (range 0 to 27), (2) emotions (range 0 to 31), (3) limitations in functioning
(range 0 to 32), or (4) because of treatment and prevention (range 0 to 27); the total score is the sum of the subscores and has a range of 0 to 117. Lower scores indicate
better outcomes. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is calculated as result –
baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.5
Table 14.2.2.4.2
Cohort 2, Pooled Treatments: Summary and Change and Percent Change from Baseline in Quality of Life in Hand Eczema Questionnaire (QOLHEQ) Subscores and Total Score
by Study Visit
ITT Population
(Same shell as Table 14.2.2.2.2; parameters include the following: Symptoms Subscore, Emotions Subscore, Limitations in Functioning Subscore, Treatment and Prevention Subscore, and
Total Score; use the below footnotes)
Abbreviations: QOLHEQ = Quality of Life in Hand Eczema Questionnaire; SD = standard deviation.
Note: Subjects are summarized by planned treatment. The construct Health Related Quality of Life (HRQOL) includes all impairments or limiting conditions caused by the
health state of an individual. The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. It consists of 30 items which can be
summarized according to these four domains: Impairments because of (1) symptoms (range 0 to 27), (2) emotions (range 0 to 31), (3) limitations in functioning
(range 0 to 32), or (4) because of treatment and prevention (range 0 to 27); the total score is the sum of the subscores and has a range of 0 to 117. Lower scores indicate
better outcomes. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is calculated as result –
baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.5


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 139 of 219
Table 14.2.2.4.3
Cohort 2: Summary of Quality of Life in Hand Eczema Questionnaire (QOLHEQ) Subscores and Total Score by Study Visit – ANCOVA
ITT Population
(Same shell as Table 14.2.2.2.3; parameters include the following: Symptoms Subscore, Emotions Subscore, Limitations in Functioning Subscore, Treatment and Prevention Subscore, and
Total Score; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QD = once daily;
QOLHEQ = Quality of Life in Hand Eczema Questionnaire; SE = standard error.
Note: Subjects are summarized by planned treatment. The construct Health Related Quality of Life (HRQOL) includes all impairments or limiting conditions caused by the health
state of an individual. The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. It consists of 30 items which can be
summarized according to these four domains: Impairments because of (1) symptoms (range 0 to 27), (2) emotions (range 0 to 31), (3) limitations in functioning (range 0 to 32), or
(4) because of treatment and prevention (range 0 to 27); the total score is the sum of the subscores and has a range of 0 to 117. Lower scores indicate better outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline QOLHEQ subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.5
Table 14.2.2.4.4
Cohort 2, Pooled Treatments: Summary of Quality of Life in Hand Eczema Questionnaire (QOLHEQ) Subscores and Total Score by Study Visit – ANCOVA
ITT Population
(Same shell as Table 14.2.2.2.4; parameters include the following: Symptoms Subscore, Emotions Subscore, Limitations in Functioning Subscore, Treatment and Prevention Subscore, and
Total Score; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; IGA = investigator global assessment; LS = least-squares; QOLHEQ = Quality of Life in Hand
Eczema Questionnaire; SE = standard error.
Note: Subjects are summarized by planned treatment. The construct Health Related Quality of Life (HRQOL) includes all impairments or limiting conditions caused by the health
state of an individual. The QOLHEQ is a disease specific instrument, thereby only assessing impairments caused by hand eczema. It consists of 30 items which can be
summarized according to these four domains: Impairments because of (1) symptoms (range 0 to 27), (2) emotions (range 0 to 31), (3) limitations in functioning (range 0 to 32), or
(4) because of treatment and prevention (range 0 to 27); the total score is the sum of the subscores and has a range of 0 to 117. Lower scores indicate better outcomes.
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline QOLHEQ subscore or total score (as appropriate) as independent variables. Baseline is the last non-missing measurement
taken on or before the day of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.5


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 140 of 219
Table 14.2.2.5.1
Cohort 2: Summary and Change and Percent Change from Baseline in % Body Surface Area (BSA) Affected by Disease by Study Visit
ITT Population
(Same shell as Table 14.2.2.2.1; parameters include “Dorsal BSA (Left Hand)”, “Dorsal BSA (Right Hand)”, “Palmar BSA (Left Hand)”, “Palmar BSA (Right Hand)”, and “Total Hand %
BSA”; use the below footnotes)
Abbreviations: BID = twice daily; BSA = body surface area; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by planned treatment. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand). Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline
is calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.6
Table 14.2.2.5.2
Cohort 2, Pooled Treatments: Summary and Change and Percent Change from Baseline in % Body Surface Area (BSA) Affected by Disease by Study Visit
ITT Population
(Same shell as Table 14.2.2.2.2; parameters include “Dorsal BSA (Left Hand)”, “Dorsal BSA (Right Hand)”, “Palmar BSA (Left Hand)”, “Palmar BSA (Right Hand)”, and “Total Hand %
BSA”; use the below footnotes)
Abbreviations: BSA = body surface area; SD = standard deviation.
Note: Subjects are summarized by planned treatment. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand). Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline
is calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.6


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 141 of 219
Table 14.2.2.5.3
Cohort 2: Summary of % Body Surface Area (BSA) Affected by Disease by Study Visit – ANCOVA
ITT Population
(Same shell as Table 14.2.2.2.3; parameters include “Dorsal % BSA (Left Hand)”, “Dorsal % BSA (Right Hand)”, “Palmar % BSA (Left Hand)”, “Palmar % BSA (Right Hand)”, and
“Total Hand % BSA”; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BID = twice daily; BSA = body surface area; CI = confidence interval; IGA = investigator global assessment;
LS = least-squares; QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand).
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline % BSA affected by disease as independent variables. Baseline is the last non-missing measurement taken on or before the day
of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream 0.3% QD minus vehicle cream [all dose frequencies]; ARQ-252 cream 0.3% BID minus vehicle cream [all dose frequencies];
or ARQ-252 cream 0.1% QD minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.6
Table 14.2.2.5.4
Cohort 2, Pooled Treatments: Summary of % Body Surface Area (BSA) Affected by Disease by Study Visit – ANCOVA
ITT Population
(Same shell as Table 14.2.2.2.4; parameters include “Dorsal % BSA (Left Hand)”, “Dorsal % BSA (Right Hand)”, “Palmar % BSA (Left Hand)”, “Palmar % BSA (Right Hand)”, and
“Total Hand % BSA”; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BSA = body surface area; CI = confidence interval; IGA = investigator global assessment; LS = least-squares;
SE = standard error.
Note: Subjects are summarized by planned treatment. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand).
[1] Estimates for LS means (change from baseline and difference from vehicle), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group,
pooled site group, baseline IGA grade, and baseline % BSA affected by disease as independent variables. Baseline is the last non-missing measurement taken on or before the day
of first application of study drug.
[2] P value for testing change from baseline is zero.
[3] P value for testing difference (ARQ-252 cream [all strengths/dose frequencies] minus vehicle cream [all dose frequencies] or ARQ-252 cream 0.3% [all dose frequencies]
minus vehicle cream [all dose frequencies]) in change from baseline from is zero.
Reference Listing: 16.2.6.6


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 142 of 219
Table 14.2.2.5.5
Cohort 1: Summary and Change and Percent Change from Baseline in % Body Surface Area (BSA) Affected by Disease by Study Visit
All Treated Population
(Same shell as Table 14.2.2.2.11; visits include Baseline and Week 2; parameters include “Dorsal % BSA (Left Hand)”, “Dorsal % BSA (Right Hand)”, “Palmar % BSA (Left Hand)”,
“Palmar % BSA (Right Hand)”, and “Total Hand % BSA”; use the below footnotes)
Abbreviations: BSA = body surface area; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand). Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline
is calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
Reference Listing: 16.2.6.6
Table 14.2.2.5.6
Cohort 1: Summary of % Body Surface Area (BSA) Affected by Disease by Study Visit – ANCOVA
All Treated Population
(Same shell as Table 14.2.2.2.11; visits include Baseline and Week 2; parameters include “Dorsal % BSA (Left Hand)”, “Dorsal % BSA (Right Hand)”, “Palmar % BSA (Left Hand)”,
“Palmar % BSA (Right Hand)”, and “Total Hand % BSA”; use the below footnotes)
Abbreviations: ANCOVA = analysis of covariance; BSA = body surface area; CI = confidence interval; IGA = investigator global assessment; LS = least-squares;
QD = once daily; SE = standard error.
Note: Subjects are summarized by planned treatment. Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA
(left hand), and palmar % BSA (right hand).
[1] Estimates for LS means (change from baseline), accompanying 90% and 95% CIs, and P values are from an ANCOVA with treatment group, pooled site group, baseline IGA
grade, and baseline % BSA affected by disease as independent variables. Baseline is the last non-missing measurement taken on or before the day of first application of study
drug.
[2] P value for testing change from baseline is zero.
Reference Listing: 16.2.6.6


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 143 of 219
Table 14.2.3.1
Cohort 2: Summary of Nail Dystrophy Normal-Appearing Nail Distal to Cuticle (mm) by Study Visit
Nail Dystrophy Population
Cohort 2
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Category/Statistic
Observed
Change
Observed
Change
Observed
Change
Baseline
XX
XX
XX
Nail with Worst Dystrophy
Left
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 2
XX
XX
XX
Normal Appearing Nail
Distal to Cuticle?
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal Appearing Nail
Distal to Cuticle (mm) [1]
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat this page for the remaining study drug (Vehicle Cream (All Dose Frequencies)), showing the same study visits shown here. Then continue for Weeks 4, 8, 12, and 13.
Abbreviations: BID = twice daily; CI = confidence interval; IGA = investigator global assessment; QD = once daily.
Note: Percentages are n/Number of subjects in the Nail Dystrophy population within planned treatment at each visit*100. Only subjects with nail dystrophy at baseline are
included in this table. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] Relative to an assumed baseline normal appearing nail distal to cuticle value of 0 mm.
Reference Listing: 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 144 of 219
Table 14.2.3.2
Cohort 2, Pooled Treatments: Summary of Nail Dystrophy Normal-Appearing Nail Distal to Cuticle (mm) by Study Visit
Nail Dystrophy Population
Cohort 2
Study Visit
ARQ-252 Cream
(All Strengths/Dose Frequencies)
(N=XX)
ARQ-252 Cream 0.3%
(All Dose Frequencies)
(N=XX)
Vehicle Cream
(All Dose Frequencies)
(N=XX)
Category/Statistic
Observed
Change
Observed
Change
Observed
Change
Baseline
XX
XX
XX
XX
XX
XX
Nail with Worst Dystrophy
Left
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Right
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 2
XX
XX
XX
XX
XX
XX
Normal Appearing Nail
Distal to Cuticle?
Yes
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
No
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal Appearing Nail
Distal to Cuticle (mm) [1]
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Q1, Q3
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Repeat for Weeks 4, 8, 12, and 13.
Abbreviations: CI = confidence interval; IGA = investigator global assessment.
Note: Percentages are n/Number of subjects in the Nail Dystrophy population within planned treatment at each visit*100. Only subjects with nail dystrophy at baseline are
included in this table. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
[1] Relative to an assumed baseline normal appearing nail distal to cuticle value of 0 mm.
Reference Listing: 16.2.6.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 145 of 219
Table 14.3.1.1
Cohorts 1 and 2: Summary of Treatment Emergent Adverse Events
Safety Population
Cohort 1
Cohort 2
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Maximum Severity of TEAE [1]
Grade 1 (Mild)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 2 (Moderate)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 3 (Severe)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 4 (Life-threatening consequences)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 5 (Death related to AE)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with a Related TEAE [2]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with a Related TEAE Leading to
Discontinuation of Study Drug [2]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with a TEAE Leading to
Discontinuation of Study Drug
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with a TEAE Leading to
Discontinuation of Study
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with an SAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Subjects with a Grade 5 TEAE [3]
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; QD = once daily; SAE = serious adverse event;
TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. A TEAE is defined as an AE within an onset on or after the day of study treatment
through study completion.
[1] Severity grades are reported according to the CTCAE version 4.0. Subjects are counted only once at the worst severity. If a severity designation is missing, it was considered as severe.
[2] AEs with a relationship of possibly related, probably related, likely related, or missing were considered related.
[3] A Grade 5 TEAE is a TEAE leading to death.
Reference Listing: 16.2.7.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 146 of 219
Table 14.3.1.2
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by System Organ Class and Preferred Term
Safety Population
Cohort 1
Cohort 2
System Organ Class
Preferred Term
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities;
PT = preferred term; QD = once daily; SAE = serious adverse event; SOC = system organ class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. AEs were coded using MedDRA version 23.0. A TEAE is defined as an AE within an
onset on or after the day of study treatment through study completion. Subjects are counted once for each SOC and once for each PT. AEs are displayed alphabetically by SOC, then by
descending frequency of PT within SOC, and then alphabetically by PT.
Reference Listing: 16.2.7.1
Programming note: SOC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 147 of 219
Table 14.3.1.3
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity
Safety Population
Cohort 1
Cohort 2
System Organ Class
Preferred Term
Maximum Severity [1]
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 1 (Mild)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 2 (Moderate)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 3 (Severe)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 4 (Life-threatening consequences)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 5 (Death related to AE)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 1 (Mild)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 2 (Moderate)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 3 (Severe)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 4 (Life-threatening consequences)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 5 (Death related to AE)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 1 (Mild)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Grade 2 (Moderate)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
…
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities;
PT = preferred term; QD = once daily; SOC = system organ class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. AEs were coded using MedDRA version 23.0. A TEAE is defined as an AE within an
onset on or after the day of study treatment through study completion. Subjects are counted once for each SOC and once for each PT.
[1] Severity grades are reported according to the CTCAE version 4.0. The severity shown is the greatest severity reported for a particular subject (Grade 5 [Death related to AE] > Grade 4
[Life-threatening consequences] > Grade 3 [Severe] > Grade 2 [Moderate] > Grade 1 [Mild]). AEs with a missing severity were counted as Severe. AEs are displayed alphabetically by
SOC, then by descending frequency of PT within SOC, and then alphabetically by PT.
Reference Listing: 16.2.7.1
Programming note: SOC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 148 of 219
Table 14.3.1.4
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Relationship to Study Drug
Safety Population
Cohort 1
Cohort 2
System Organ Class
Preferred Term
Relationship [1]
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 TEAE
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
System Organ Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Not Related
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
…
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities;
PT = preferred term; QD = once daily; SAE = serious adverse event; SOC = system organ class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. AEs were coded using MedDRA version 23.0. A TEAE is defined as an AE within an
onset on or after the day of study treatment through study completion. Subjects are counted once for each SOC and once for each PT at the greatest relationship category. The relationship
shown is the greatest relationship reported for a particular subject (Related > Not Related). AEs with a missing relationship were counted as Related. AEs are displayed alphabetically by
SOC, then by descending frequency of PT within SOC, and then alphabetically by PT.
[1] Related = Probably Related, Possibly Related, Likely Related, and missing; Not Related = Unrelated and Unlikely Related.
Reference Listing: 16.2.7.1
Programming note: SOC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 149 of 219
Table 14.3.1.5
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and Preferred Term
Safety Population
(Same shell as Table 14.3.1.2)
Table 14.3.1.6
Cohorts 1 and 2: Incidence of Related Treatment Emergent Adverse Events Leading to Study Drug Discontinuation by System Organ Class and Preferred Term
Safety Population
(Same shell as Table 14.3.1.2; use the below footnotes)
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities;
PT = preferred term; QD = once daily; SOC = system organ class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. AEs were coded using MedDRA version 23.0. A TEAE is defined as an AE within an
onset on or after the day of study treatment through study completion. Related TEAEs are AE marked Probably Related, Possibly Related, Likely Related, or missing. Subjects are counted
once for each SOC and once for each PT. AEs are displayed alphabetically by SOC, then by descending frequency of PT within SOC, and then alphabetically by PT.
Reference Listing: 16.2.7.1
Table 14.3.1.7
Cohorts 1 and 2: Incidence of Treatment Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term
Safety Population
(Same shell as Table 14.3.1.2)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 150 of 219
Table 14.3.1.8
Cohorts 1 and 2: Incidence of Related Treatment Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity
Safety Population
(Same shell as Table 14.3.1.3; updated 1st line of the table to say, “Subjects with at least 1 Related TEAE”; use the below footnotes)
Abbreviations: AE = adverse event; BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; MedDRA = Medical Dictionary for Regulatory Activities;
PT = preferred term; QD = once daily; SAE = serious adverse event; SOC = system organ class; TEAE = treatment emergent adverse event.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. AEs were coded using MedDRA version 23.0. A TEAE is defined as an AE within an
onset on or after the day of study treatment through study completion. Related TEAEs are AE marked Probably Related, Possibly Related, Likely Related, or missing. Subjects are counted
once for each SOC and once for each PT.
[1] Severity grades are reported according to the CTCAE version 4.0. The severity shown is the greatest severity reported for a particular subject (Grade 5 [Death related to AE] > Grade 4
[Life-threatening consequences] > Grade 3 [Severe] > Grade 2 [Moderate] > Grade 1 [Mild]). AEs with a missing severity were counted as Severe. AEs are displayed alphabetically by
SOC, then by descending frequency of PT within SOC, and then alphabetically by PT.
Reference Listing: 16.2.7.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 151 of 219
Table 14.3.2.1
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ Class and Preferred Term
Safety Population
(Same shell as Table 14.3.1.2; first-row text is “Subjects with at least 1 SAE”; add SAE = serious adverse event)
Table 14.3.2.2
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ Class, Preferred Term, and Maximum Severity
Safety Population
(Same shell as Table 14.3.1.3; first-row text is “Subjects with at least 1 SAE”; add SAE = serious adverse event)
Table 14.3.2.3
Cohorts 1 and 2: Incidence of Serious Adverse Events by System Organ Class, Preferred Term, and Relationship to Study Drug
Safety Population
(Same shell as Table 14.3.1.4; first-row text is “Subjects with at least 1 SAE”; add SAE = serious adverse event)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 152 of 219
Table 14.3.3.1
Listing of Adverse Events Leading to Study Drug Discontinuation
Safety Population
Cohort: Cohort x
Subject
ID
Treatment [1]
TEAE?
System Organ Class/
Preferred Term/
Verbatim Term
Start Date/Time (Study Day)/
End Date/Time (Study Day)
CTCAE Toxicity Grade/
Relationship
Outcome/
Action Taken/
Other Action Taken
Serious?
AE Lead to
Study D/C?
XXXXX
XXXXXX
XXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXX
XXXXXXXXXX
DDMMMYYYY/hh:mm (X)/
DDMMMYYYY/ hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XX
XX
XXXXX
XXXXXX
XXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY/ hh:mm (X)/
DDMONYYYY/ hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XX
XX
XX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMONYYYY/ hh:mm (X)/
Ongoing
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XXX
XXX
Abbreviations: BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; D/C = discontinuation; MedDRA = Medical Dictionary for Regulatory Activities; QD = once daily;
TEAE = treatment emergent adverse event.
Note: Study day is calculated relative to the date of first application of study drug. AEs were coded using MedDRA version 23.0. Severity grades are reported according to the CTCAE version 4.0.
All AEs with an onset on or after the day of study treatment through study completion are considered as TEAEs.
[1] Treatment received for both cohorts.
Programming note: If time missing, display “- -:- -”. “Other Action Taken” will be either None, Concomitant Medication, Non-drug Therapy, Hospitalization or Prolongation of Hospitalization,
Discontinued Study or Other; if specify text is needed, concatenate “Concomitant Medication:” or “Other:” with the text. If no events meet the criteria for display, present “No adverse events leading
to study drug discontinuation were reported for this study.” SOC & PT text should presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 153 of 219
Table 14.3.3.2
Listing of Serious Adverse Events
Safety Population
(Same shell as Table 14.3.3.1; if no events meet the criteria for display, present “No serious adverse events were reported for this study.”)
Table 14.3.3.3
Listing of Deaths
Safety Population
(Same shell as Table 14.3.3.1; if no events meet the criteria for display, present “No deaths were reported for this study.”)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 154 of 219
Table 14.3.5.1.1.1
Cohort 1: Summary of Clinical Chemistry Laboratory Results (Standard Units) by Study Visit
Safety Population
Parameter: XXXXXXXXXXXX (unit)
Cohort 1
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
Statistic
Observed
Change
Baseline
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Week 1
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Week 2
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Week 3
n
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Continue for other parameters. Sort alphabetically by parameter.
Abbreviations: QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Results from the thyroid panel are included.
Baseline is the last non-missing measurement taken before the first application of study drug.
Change from baseline is calculated as result – baseline result.
Reference Listings: 16.2.8.1.1, 16.2.8.1.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 155 of 219
Table 14.3.5.1.1.2
Cohort 2: Summary of Clinical Chemistry Laboratory Results (Standard Units) by Study Visit
Safety Population
Parameter: XXXXXXXXXXXX (unit)
Cohort 2
Study Visit
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Statistic
Observed
Change
Observed
Change
Observed
Change
Baseline
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Week 4
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Week 8
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Week 12
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Repeat this page for the remaining study drugs (Vehicle Cream QD and Vehicle Cream BID), showing the same study visits shown here. Continue for other parameters.
Sort alphabetically by parameter.
Abbreviations: BID = twice daily; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Results from the thyroid panel are included. Baseline is the last non-missing measurement taken before the first
application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listings: 16.2.8.1.1, 16.2.8.1.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 156 of 219
Table 14.3.5.1.2.1
Cohort 1: Shift from Baseline in Clinical Chemistry Laboratory Results (Standard Units) by Study Visit
Safety Population
Parameter: XXXXXXX (unit)
Baseline Grade
Cohort 1
Post-
Baseline
ARQ-252 Cream 0.3% QD
(N=XX)
Study Visit
Grade
Missing
Low
Normal
High
Total
Week 1
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 2
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 3
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Repeat all for clinical chemistry parameters (excluding serum HCG results).
Abbreviation: QD = once daily.
Note: Subjects are summarized by treatment received. Results from the thyroid panel are included. Baseline is the last
non-missing measurement taken before the first application of study drug.
Reference Listings: 16.2.8.1.1, 16.2.8.1.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 157 of 219
Table 14.3.5.1.2.2
Cohort 2: Shift from Baseline in Clinical Chemistry Laboratory Results (Standard Units) by Study Visit
Safety Population
Parameter: XXXXXXX (unit)
Baseline Grade
Cohort 2
Post-
Baseline
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
Study Visit
Grade
Missing
Low
Normal
High
Total
Missing
Low
Normal
High
Total
Week 4
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 8
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 12
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Low
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
High
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Repeat this page for the remaining study drugs (ARQ-252 Cream 0.1% QD, Vehicle Cream QD, and Vehicle Cream BID), showing the same study visits shown here. Repeat all for clinical chemistry
parameters (excluding serum HCG results).
Abbreviations: BID = twice daily; QD = once daily.
Note: Subjects are summarized by treatment received. Results from the thyroid panel are included. Baseline is the last non-missing measurement taken before the first application of study drug.
Reference Listings: 16.2.8.1.1, 16.2.8.1.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 158 of 219
Table 14.3.5.2.1.1
Cohort 1: Summary of Hematology Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.1; Reference Listing: 16.2.8.1.2)
Table 14.3.5.2.1.2
Cohort 2: Summary of Hematology Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.2; Reference Listing: 16.2.8.1.2)
Table 14.3.5.2.2.1
Cohort 1: Shift from Baseline in Hematology Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.2.1; Reference Listing: 16.2.8.1.2)
Table 14.3.5.2.2.2
Cohort 2: Shift from Baseline in Hematology Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.2.2; Reference Listing: 16.2.8.1.2)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 159 of 219
Table 14.3.5.3.1.1
Cohort 1: Summary of Quantitative Urinalysis Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.1; Reference Listing: 16.2.8.1.3)
Table 14.3.5.3.1.2
Cohort 2: Summary of Quantitative Urinalysis Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.2; Reference Listing: 16.2.8.1.3)
Table 14.3.5.3.2.1
Cohort 1: Shift from Baseline in Quantitative and Qualitative Urinalysis Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.2.1; Reference Listing: 16.2.8.1.3)
Table 14.3.5.3.2.2
Cohort 2: Shift from Baseline in Quantitative and Qualitative Urinalysis Laboratory Results (Standard Units) by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.2.2; Reference Listing: 16.2.8.1.3)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 160 of 219
Table 14.3.5.3.3.1
Cohort 1: Summary of Qualitative Urinalysis Laboratory Results by Study Visit
Safety Population
Parameter: XXXXXXXXXXXX (unit)
Cohort 1
Study Visit
Category
ARQ-252 Cream 0.3%
QD
(N=XX)
Baseline
XXXXXXXXXX
XX (XX.X%)
XXXXXXXXXXXX
XX (XX.X%)
Week 1
XXXXXXXXX
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
Week 2
XXXXXXXXX
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
Week 3
XXXXXXXXX
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
Abbreviation: QD = once daily; TNTC = too numerous to count.
Note: Percentages are n/Number of subjects in the Safety population within treatment
received*100. Baseline is the last non-missing measurement taken before the first
application of study drug.
Reference Listing: 16.2.8.1.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 161 of 219
Table 14.3.5.3.3.2
Cohort 2: Summary of Qualitative Urinalysis Laboratory Results by Study Visit
Safety Population
Parameter: XXXXXXXXXXXX (unit)
Cohort 2
Study Visit
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Baseline
XXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 4
XXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 8
XXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 12
XXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XXXXXXXX
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; QD = once daily; TNTC = too numerous to count.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. Baseline is the last non-missing measurement taken before the
first application of study drug.
Reference Listing: 16.2.8.1.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 162 of 219
Table 14.3.6.1.1
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment (Dermal Response) by Study Visit
Safety Population
Cohort 1
Cohort 2
Study Visit
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
Statistic
Observed
Change
Observed
Change
Observed
Change
Baseline
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Week 1
n
XX
XX
NA
NA
NA
NA
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
Min, Max
XX, XX
XX, XX
Week 2
n
XX
XX
XX
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
XX, XX
Repeat this page for the remaining Cohort 2 study drugs (ARQ-252 Cream 0.1% QD, Vehicle Cream QD, and Vehicle Cream BID),
showing the same study visits shown here. Continue for the following study visits, applicable to Cohort 2 only: Week 4, Week 8, and Week
12; put “NA” in the “n” row for Cohort 1 for these visits.
Abbreviations: BID = twice daily; NA = not applicable; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. The Week 1 study visit is only applicable to Cohort 1 subjects; the Week 4 through
Week 12 study visits are only applicable to Cohort 2 subjects. Lower scores indicate no evidence of irritation while higher scores indicate
worsening reaction. These assessments should be done prior to the study drug application in the study site. Subjects not meeting this condition
on baseline visit are completely removed from the table summary. Baseline is the last non-missing measurement taken before the first
application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.9.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 163 of 219
Table 14.3.6.1.2
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment (Dermal Response) by Study Visit
Categorical Results
Safety Population
Cohort 1
Cohort 2
Study Visit
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Baseline
XX
XX
XX
XX
XX
XX
0 = No evidence of irritation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Minimal erythema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Definite erythema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Erythema and papules
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
4 = Definite edema
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
5 = Erythema, edema and papules
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
6 = Vesicular eruption
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
7 = Strong reaction spreading beyond
application site
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 1
XX
NA
NA
NA
NA
NA
0 = No evidence of irritation
XX (XX.X%)
1 = Minimal erythema
XX (XX.X%)
2 = Definite erythema
XX (XX.X%)
3 = Erythema and papules
XX (XX.X%)
4 = Definite edema
XX (XX.X%)
5 = Erythema, edema and papules
XX (XX.X%)
6 = Vesicular eruption
XX (XX.X%)
7 = Strong reaction spreading beyond
application site
XX (XX.X%)
Week 2
XX
XX
XX
XX
XX
XX
0 = No evidence of irritation
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
…
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Continue for the following study visits, applicable to Cohort 2 only: Week 4, Week 8, and Week 12; put “NA” in the study visit row for Cohort 1 for these visits.
Abbreviations: BID = twice daily; NA = not applicable; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received, study visit, and overall*100. The Week 1 study visit is only applicable to Cohort 1 subjects;
the Week 4 through Week 12 study visits are only applicable to Cohort 2 subjects. These assessments should be done prior to the study drug application in the study site. Subjects not
meeting this condition on baseline visit are completely removed from the table summary. Baseline is the last non-missing measurement taken before the first application of study drug.
Reference Listing: 16.2.9.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 164 of 219
Table 14.3.6.1.3
Cohorts 1 and 2: Summary of Investigator Local Tolerability Assessment (Other Effects) by Study Visit
Categorical Results
Safety Population
Cohort 1
Cohort 2
Study Visit
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Baseline
XX
XX
XX
XX
XX
XX
A = Slight glazed appearance
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
B = Marked glazing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
C = Glazing with peeling and cracking
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
D = Glazing with fissures
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
E = Film of dried serous exudates
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
F = Small petechial erosions and/or scabs
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
G = No other effects
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 1
XX
NA
NA
NA
NA
NA
A = Slight glazed appearance
XX (XX.X%)
B = Marked glazing
XX (XX.X%)
C = Glazing with peeling and cracking
XX (XX.X%)
D = Glazing with fissures
XX (XX.X%)
E = Film of dried serous exudates
XX (XX.X%)
F = Small petechial erosions and/or scabs
XX (XX.X%)
G = No other effects
XX (XX.X%)
Week 2
XX
XX
XX
XX
XX
XX
A = Slight glazed appearance
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
…
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Continue for the following study visits, applicable to Cohort 2 only: Week 4, Week 8, and Week 12; put “NA” in the study visit row for Cohort 1 for these visits.
Abbreviations: BID = twice daily; NA = not applicable; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received, study visit, and overall*100. The Week 1 study visit is only applicable to Cohort 1 subjects;
the Week 4 through Week 12 study visits are only applicable to Cohort 2 subjects. These assessments should be done prior to the study drug application in the study site. Subjects not
meeting this condition on baseline visit are completely removed from the table summary. Baseline is the last non-missing measurement taken before the first application of study drug.
Reference Listing: 16.2.9.1


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 165 of 219
Table 14.3.6.2.1
Cohorts 1 and 2: Summary of Subject Local Tolerability Assessment by Study Visit
Safety Population
(Same shell as Table 14.3.6.1.1; use the below footnotes)
Abbreviations: BID = twice daily; NA = not applicable; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. The Week 1 study visit is only applicable to Cohort 1 subjects; the Week 2 through Week 12 study visits are only applicable to Cohort
2 subjects. These assessments should be done 10 - 15 minutes after the application of study drug at the study site. Subjects not meeting this condition on baseline visit are completely
removed from the table summary. Baseline is the first non-missing measurement taken after the first application of study drug. Change from baseline is calculated as result – baseline result.
Reference Listing: 16.2.9.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 166 of 219
Table 14.3.6.2.2
Cohorts 1 and 2: Summary of Subject Local Tolerability Assessment by Study Visit
Categorical Results
Safety Population
Cohort 1
Cohort 2
Study Visit
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Baseline
XX
XX
XX
XX
XX
XX
0 = None (no sensation)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
1 = Mild (slight warm, tingling sensation)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
2 = Moderate (definite warm, tingling
sensation)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
3 = Severe (hot, tingling/stinging
sensation)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 1
XX
NA
NA
NA
NA
NA
0 = None (no sensation)
XX (XX.X%)
1 = Mild (slight warm, tingling sensation)
XX (XX.X%)
2 = Moderate (definite warm, tingling
sensation)
XX (XX.X%)
3 = Severe (hot, tingling/stinging
sensation)
XX (XX.X%)
Week 2
XX
XX
XX
XX
XX
XX
0 = None (no sensation)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
…
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Continue for the following study visits, applicable to Cohort 2 only: Week 4, Week 8, and Week 12; put “NA” in the study visit row for Cohort 1 for these visits.
Abbreviations: BID = twice daily; NA = not applicable; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety Population within treatment received, study visit, and overall*100. The Week 1 study visit is only applicable to Cohort 1 subjects;
the Week 4 through Week 12 study visits are only applicable to Cohort 2 subjects. These assessments should be done 10 - 15 minutes after the application of study drug at the study site.
Subjects not meeting this condition on baseline visit are completely removed from the table summary. Baseline is the first non-missing measurement taken after the first application of study
drug.
Reference Listing: 16.2.9.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 167 of 219
Table 14.3.6.3.1
Cohort 1: Summary of Vital Signs by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.1; study visits include Baseline, Week 1, Week 2, and Week 3; parameters include Temperature (°C), Heart Rate (bpm), Systolic Blood Pressure (mmHg),
Diastolic Blood Pressure (mmHg), Height (cm), Weight (kg), and Body Mass Index (kg/m2) [1]; use the below footnotes)
Abbreviation: QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is
calculated as result – baseline result.
[1] Body Mass Index (BMI) = weight (kg) / [height (m)]2.
Reference Listing: 16.2.9.3
Table 14.3.6.3.2
Cohort 2: Summary of Vital Signs by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.2; study visits include Baseline, Week 2, Week 4, Week 8, Week 12, and Week 13; parameters include Temperature (°C), Heart Rate (bpm), Systolic Blood
Pressure (mmHg), Diastolic Blood Pressure (mmHg), Height (cm), Weight (kg), and Body Mass Index (kg/m2) [1]; use the below footnotes)
Abbreviations: BID = twice daily; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from baseline is
calculated as result – baseline result.
[1] Body Mass Index (BMI) = weight (kg) / [height (m)]2.
Reference Listing: 16.2.9.3


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 168 of 219
Table 14.3.6.4.1.1
Cohort 1: Summary of 12-Lead Electrocardiogram by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.1; study visits include Baseline and Week 2; parameters include PR Interval (msec), QRS Interval (msec), QT Interval (msec), QTcF Interval (msec), and
Heart Rate (bpm); use the below footnotes)
Abbreviation: QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Baseline is the last non-missing measurement taken before the first application of study drug. Change from baseline is calculated as
result – baseline result.
Reference Listing: 16.2.9.4
Table 14.3.6.4.1.2
Cohort 2: Summary of 12-Lead Electrocardiogram by Study Visit
Safety Population
(Same shell as Table 14.3.5.1.1.2; study visits include Baseline, Week 4, and Week 12; parameters include PR Interval (msec), QRS Interval (msec), QT Interval (msec), QTcF Interval
(msec), and Heart Rate (bpm); use the below footnotes)
Abbreviations: BID = twice daily; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Baseline is the last non-missing measurement taken before the first application of study drug. Change from baseline is calculated as
result – baseline result.
Reference Listing: 16.2.9.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 169 of 219
Table 14.3.6.4.2.1
Cohort 1: Summary of 12-Lead Electrocardiogram Interpretation by Study Visit
Safety Population
Cohort 1
Study Visit
Category
ARQ-252 Cream 0.3%
QD
(N=XX)
Baseline
Normal
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
Missing
XX (XX.X%)
Total
XX (XX.X%)
Week 2
Normal
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
Missing
XX (XX.X%)
Total
XX (XX.X%)
Abbreviation: CS = clinically significant; NCS = not clinically significant;
QD = once daily.
Note: Percentages are n/Number of subjects in the Safety population within treatment
received*100. Baseline is the last non-missing measurement taken before the first
application of study drug.
Reference Listing: 16.2.9.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 170 of 219
Table 14.3.6.4.2.2
Cohort 2: Summary of 12-Lead Electrocardiogram Interpretation by Study Visit
Safety Population
Cohort 2
Study Visit
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Baseline
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 4
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Week 12
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: BID = twice daily; CS = clinically significant; NCS = not clinically significant; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. Baseline is the last non-missing measurement taken before the
first application of study drug.
Reference Listing: 16.2.9.4


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 171 of 219
Table 14.3.6.5.1
Cohort 1: Summary of Physical Examination by Study Visit
Safety Population
Cohort 1
Study Visit
Body System
Category
ARQ-252 Cream 0.3%
QD
(N=XX)
Screening
Skin
Normal
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
Missing
XX (XX.X%)
Total
XX (XX.X%)
Lungs
Normal
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
Missing
XX (XX.X%)
Total
XX (XX.X%)
Heart
Normal
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
Missing
XX (XX.X%)
Total
XX (XX.X%)
Repeat for Baseline, Day 8, Week 2, and Week 3.
Abbreviations: CS = clinically significant; NCS = not clinically significant;
QD = once daily.
Note: Percentages are n/Number of subjects in the Safety population within treatment
received*100. Baseline is the last non-missing measurement taken on or before the day
of first application of study drug.
Reference Listing: 16.2.9.5


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 172 of 219
Table 14.3.6.5.2
Cohort 2: Summary of Physical Examination by Study Visit
Safety Population
Cohort 2
Study Visit
Body System
Category
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Screening
Skin
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Lungs
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Heart
Normal
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (NCS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abnormal (CS)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Missing
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Total
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Repeat for Baseline and Week 12.
Abbreviations: BID = twice daily; CS = clinically significant; NCS = not clinically significant; QD = once daily.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. Baseline is the last non-missing measurement taken on or
before the day of first application of study drug.
Reference Listing: 16.2.9.5


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 173 of 219
Table 14.3.6.6
Cohorts 1 and 2: Summary of Concomitant Medications by ATC Class Level 4 and Preferred Term
Safety Population
Cohort 1
Cohort 2
ATC Class Level 4
Preferred Term
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% QD
(N=XX)
ARQ-252 Cream
0.3% BID
(N=XX)
ARQ-252 Cream
0.1% QD
(N=XX)
Vehicle Cream QD
(N=XX)
Vehicle Cream
BID
(N=XX)
Subjects with at least 1 Concomitant Medication
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
ATC Class 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
ATC Class 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 1
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 2
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Preferred Term 3
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
XX (XX.X%)
Abbreviations: ATC = Anatomic Therapeutic Chemical; BID = twice daily; PT = preferred term; QD = once daily; WHO-DDE = World Health Organization-Drug Dictionary Enhanced.
Note: Percentages are n/Number of subjects in the Safety population within treatment received*100. Medications were coded using WHO-DDE Global B3 version September 2019.
Concomitant medications are all medications that were continuing or starting after first application of study drug. Medications are displayed by alphabetical order of ATC Level 4
classification, then descending frequency of PT within ATC, and then alphabetically by PT. Subjects were counted only once for each ATC and PT.
[1] ATC Level 4 was not definable for these preferred terms due to multiple ingredients that cannot be mapped to an ATC Level 4 term, route of administration and indication that is not
defined in an ATC Level 4 term, or some similar circumstance.
Reference Listing: 16.2.9.7
Programming note: ATC & PT text should be presented as is from the dataset. If medications are coded but are missing ATC Class Level 4, display as “NOT DEFINED [1]” in the ATC Class Level 4
row and include footnote [1]; otherwise remove footnote [1] from the table.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 174 of 219
Table 14.4.1.1
Cohort 1: Summary of Pharmacokinetic Results by Study Visit and Time Point
PK Population
Study Visit
Time Point
Statistic
Cohort 1
ARQ-252 Cream 0.3% QD
(N=XX)
Day 1
Predose
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
1 hour postdose
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
2 hours postdose
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
4 hours post dose
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Repeat for Day 1: 4 hours postdose, 6 hours postdose, and 24 hours postdose; Day 8:
Predose; Week 2: Predose, 1 hour postdose, 2 hours postdose, 4 hours postdose, 6 hours
postdose, and 24 hours postdose.
Abbreviations: QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Results at any predose time points that
occurred after dosing are excluded from this summary.
Reference Listings: 16.2.5.6.1, 16.2.5.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 175 of 219
Table 14.4.1.2
Cohort 2: Summary of Pharmacokinetic Results by Study Visit and Time Point
PK Population
Study Visit
Cohort 2
Time Point
Statistic
ARQ-252 Cream 0.3% QD
(N=XX)
ARQ-252 Cream 0.3% BID
(N=XX)
ARQ-252 Cream 0.1% QD
(N=XX)
Day 1
Predose
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Week 4
Predose
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Week 12
Predose
n
XX
XX
XX
Mean (SD)
XX.X (X.XX)
XX.X (X.XX)
XX.X (X.XX)
Median
XX.X
XX.X
XX.X
Min, Max
XX, XX
XX, XX
XX, XX
Abbreviations: BID = twice daily; QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received. Results at any predose time points that occurred after dosing are excluded from this summary.
Reference Listings: 16.2.5.6.1, 16.2.5.6.2


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 176 of 219
Table 14.4.2
Cohort 1: Summary of Pharmacokinetic Parameters by Study Visit
PK Population
Parameter: XXXXXXXXXXX (unit)
Study Visit
Statistic
Cohort 1
ARQ-252 Cream 0.3% QD
(N=XX)
Day 1
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Week 2
n
XX
Mean (SD)
XX.X (X.XX)
Median
XX.X
Min, Max
XX, XX
Abbreviations: QD = once daily; SD = standard deviation.
Note: Subjects are summarized by treatment received.
Reference Listing: 16.2.5.7


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 177 of 219
14.3.
Planned Listing Shells


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 178 of 219
Listing 16.2.1.1
Subject Disposition
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
Did Subject
Complete
Study?
Date of
Completion/
Early Termination
(Study Day)
Reason for Early
Termination
Date of Death/
Cause of Death
Early Termination
due to COVID-19
Disruption
Date of Last
Dose
(Study Day)
XXXX
XXXXX
Yes
DDMMMYYYY
(XX)
XX
DDMMMYYYY
(XX)
XXXX
XXXXX
Yes
DDMMMYYYY
(XX)
XX
DDMMMYYYY
(XX)
XXXX
XXXXX
Yes
DDMMMYYYY
(XX)
XX
DDMMMYYYY
(XX)
XXXX
XXXXX
Ongoing
XXXX
XXXXX
No
DDMMMYYYY
(XX)
XXXXXX
DDMMMYYYY /
XXXXXXX
XX
DDMMMYYYY
(XX)
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
Programming note: If reason for early termination is Other, concatenate the specify text as follows: “Other: XXXXXXXXX”.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 179 of 219
Listing 16.2.1.2
Subject Visits
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Was Visit
Performed?
Study Visit
Visit Date
(Study Day)
If Visit not Performed, COVID-
19 Disruption Contributed to
Missed Visit
XXXXXX
XXXXXX
Yes
XXXXXXX
DDMMMYYYY (XX)
Yes
XXXXXX
DDMMMYYYY (XX)
Yes
XXXXXXXXX
DDMMMYYYY (XX)
No
XXXXXXX
Yes
XXXXXX
XXXXXX
Yes
XXXXXXX
DDMMMYYYY (XX)
Yes
XXXXXX
DDMMMYYYY (XX)
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 180 of 219
Listing 16.2.2.1
Inclusion and Exclusion Criteria
All Subjects
Cohort: Cohort x
Subject Screen Failed
Date/Time (Study Day) of:
All Inclusion
Criteria Met?
[2]
Any Exclusion
Criteria Met?
[3]
Subject ID
due to COVID-19
Disruption
Treatment [1]
Screening
Informed Consent
XXXXXX
XX
XXXXXX
DDMMMYYYY
(-X)
DDMMMYYYY/hh:mm
(-X)
Yes
No
XXXXXX
XX
DDMMMYYYY
DDMMMYYYY/hh:mm
No: 02, 10
No
XXXXXX
XX
DDMMMYYYY
DDMMMYYYY/hh:mm
No: 01
No
XXXXXX
XXX
XXXXXX
DDMMMYYYY
(-X)
DDMMMYYYY/hh:mm
(-X)
Yes
Yes: 03
XXXXXX
XX
XXXXXX
DDMMMYYYY
(-X)
DDMMMYYYY
(-X)
Yes
No
XXXXXX
XX
XXXXXX
DDMMMYYYY
(-X)
DDMMMYYYY
(-X)
Yes
No
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] 01 = Participants legally competent to sign and give informed consent; 02 = Males and females 18 years of age and older (inclusive) at the time of consent;
10 = Subjects are considered reliable and capable of adhering to the Protocol and visit schedule according to the Investigator judgment.
[3] 03 = Subjects with any presence or history of psoriasis.
Programming note: If more than 1 inclusion or exclusion criterion number exists, concatenate with a comma as shown above. Decode any relevant criteria in the footnotes as shown in the example. If
no criteria are present for a column, remove the [2] and/or [3] from the column header. Time is only collected for informed consent. If time is missing, display as shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 181 of 219
Listing 16.2.2.2
Protocol Deviations
All Subjects
Cohort: Cohort x
Subject ID
Treatment
[1]
Event Type
Violation Level [2] Description
COVID-19 Related
COVID-19 Infection
Action/Resolution
XXXXXX
XXXXXX
XXXXXXXXXXX
XXXXXX
XXXXXXX
XXX
XXX
XXXXXXX
XXXXXXXXXXXXX
X
XXXXXX *
XXXXXXXXXXXXXXX
XXXX
XXXX
XXXXXXX
XXXXXX
XXXXXX
XXXXXXXXXXXX
XXXXXX
XXXXXXXXXXXXXXXXXXX
XXXX
XXXX
XXXXXXX
XXXXXXXXXXXXX
XX
XXXXXX
XXXXXXXXXXX
XXXX
XXXX
XXXXXXX
XXXXXX
XXXXXX
XXXXXXXXXXXX
XXXXXX
XXXXXXXXXXXXXXXXXXXX
XXXX
XXXX
XXXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
[1] Treatment received for both cohorts.
[2] * = led to exclusion from Per Protocol population.
Programming note: The structure of this listing may change depending on the information in the protocol deviations file. If a PD is responsible for exclusion from PP population, concatenate violation
level with a * as shown above.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 182 of 219
Listing 16.2.3.1
Subject Randomization
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Randomization
Randomized
Treatment
Date/Time
Number
Stratification ID
XXXXXX
XXXXXX
XXXXX
DDMMMYYY/
hh:mm
XXXX
XXXX
XXXXXX
XXXXXXX
XXXXX
DDMMMYYY/
hh:mm
XXXX
XXXX
XXXXXX
Abbreviation: BID = twice daily; QD = once daily.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 183 of 219
Listing 16.2.3.2
Analysis Populations
All Subjects
Cohort: Cohort x
Subject ID
Treatment
[1]
Safety
[2]
All
Treated
[3]
ITT
[4]
PP
[5]
PRU4
[6]
PNRS4
[7]
PNRS3
[8]
PNRS2
[9]
ND
[10]
PK
[11]
Primary Reason(s) for Exclusion [12]
XXXXXX
XXXXXX
Yes
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXXXXX
XXXXXXX
Yes
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXXXXX
No
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
Subject did not receive at least 1 dose of IP.
Abbreviations: BID = twice daily; ITT = intent-to-treat; IP = investigational product; NA = not applicable; ND = nail dystrophy; NRS = Numeric Rating Scale; PK = pharmacokinetic; PRU4 = Subjects with
WI-NRS Pruritus Score ≥4 at Baseline; PNRS2 = Subjects with Pain NRS Score ≥2 at Baseline; PNRS3 = Subjects with Pain NRS Score ≥3 at Baseline; PNRS4 = Subjects with Pain NRS Score ≥4 at Baseline;
QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
[1] Treatment received for both cohorts.
[2] The Safety Population includes all subjects who are enrolled and received at least 1 confirmed dose of IP.
[3] The All Treated Population includes all subjects in the Safety population in Cohort 1.
[4] The ITT Population includes all subjects who are randomized to Cohort 2.
[5] The PP population includes all subjects in the Safety population in Cohort 2, who were at least 80% compliant with study medication application, and showed no important deviations from the study protocol
that would affect the interpretation of efficacy.
[6] The PRU4 population is a subset of the ITT population and includes subjects with WI-NRS pruritus score ≥4 at Baseline. This population is used for the analyses of achievement of a 4-point reduction in
WI-NRS pruritus score as compared to Baseline.
[7] The PNRS4 population is a subset of the ITT population and includes subjects with Pain NRS score ≥4 at Baseline. This population is used for the analyses of achievement of a 4-point reduction in Pain NRS
pruritus score as compared to Baseline.
[8] The PNRS3 population is a subset of the ITT population and includes subjects with Pain NRS score ≥3 at Baseline. This population is used for the analyses of achievement of a 3-point reduction in Pain NRS
pruritus score as compared to Baseline.
[9] The PNRS2 population is a subset of the ITT population and includes subjects with Pain NRS score ≥2 at Baseline. This population is used for the analyses of achievement of a 2-point reduction in Pain NRS
pruritus score as compared to Baseline.
[10] The ND population is a subset of the ITT population and includes subjects with nail dystrophy at Baseline. This population is used for the analyses of nail dystrophy as compared to Baseline.
[11] The PK population includes all subjects receiving the active drug with sufficient plasma concentrations of ARQ-254 to define a profile, as determined by the pharmacokineticist.
[12] Applies to the Safety, ITT, and PP populations only.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 184 of 219
Listing 16.2.4.1.1
Subject Demographics
All Subjects
Cohort: Cohort x
Child-Bearing
Potential? If
Yes, Specify
Contraception
Year of
Birth
Age
(years)
Was
Photography
Consent
Obtained?
Photography
Consent Date
Subject
ID
Treatment
[1]
Sex
Is Subject Post
Menopausal?
Ethnicity
Race
XXXXX
X
XXXXXX
XXXXX
No
Yes
YYYY
XX
XXXXX
X
XXXXX
X
Yes
DDMMMYYYY
XXXXX
X
XXXXXX
XXXXX
No
Yes
YYYY
XX
XXXXX
X
XXXXX
X
Yes
DDMMMYYYY
XXXXX
X
XXXXXX
XXXX
YYYY
XX
XXXXX
X
XXXXX
X
No
XXXXX
X
XXXXXX
XXXX
YYYY
XX
XXXXX
X
XXXXX
Yes
DDMMMYYYY
XXXXX
X
XXXXXX
XXXXX
No
Yes
YYYY
XX
XXXXX
X
XXXXX
X
Yes
DDMMMYYYY
XXXXX
X
XXXXXX
XXXXX
Yes:
XXXXXXX;
XXXX
No
YYYY
XX
XXXXX
X
XXXXX
X
XXX
DDMMMYYYY
Abbreviations: BID = twice daily; QD = once daily.
Note: Age at Screening.
[1] Treatment received for both cohorts.
Programming note: If subject has multiple races, concatenate them. If child-bearing potential is Yes, concatenate type of contraception with “:” as shown in the shell. Concatenate method of
contraception and type of barrier method if answered, as shown in the shell with “;”.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 185 of 219
Listing 16.2.4.1.2
Baseline Characteristics
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Height (cm)
Weight (kg)
Total
Hand BSA
(%)
IGA [2]
WI-NRS [3]
Pain NRS [3]
HECSI Total
Score [2]
QOLHEQ Total
Score [2]
Nail with Worst
Dystrophy [2]
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX
XX
XX
XX
XX
XXXXX
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX *
XX
XX
XX
XX
XXXX
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX
XX
XX
XX
XX
XXXX
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX
XX
XX
XX
XX
XXXXX
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX
XX
XX
XX
XX
XXXXX
XXXXXX
XXXXXX
XX.X
XX.X
XX.X
X = XXXXX
XX
XX
XX
XX
XXXX
Abbreviations: BID = twice daily; BSA = body surface area; HECSI = Hand Eczema Severity Index; IGA = investigator global assessment; N/A = not applicable; NRS = Numeric Rating Scale;
QD = once daily; QOLHEQ = Quality of Life in Hand Eczema Questionnaire; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: % BSA affected by disease are the values at Screening. Height and Weight are the values at Baseline Day 1.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] Baseline result, where baseline is the last non-missing measurement taken on or before the day of first application of study drug. * = Screening visit was used as baseline.
[3] Baseline result, where baseline is the last non-missing measurement taken before the day of first application of study drug.
Programming note: For efficacy scores, if VISIT is not Baseline Day 1 for the record where ABLFL=Y, then add a * to the end of the concatenated numeric + text result, as shown in the
shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 186 of 219
Listing 16.2.4.2.1
Medical History
All Subjects
Cohort: Cohort x
Subject ID
Treatment
[1]
System Organ Class/
Preferred Term/
Verbatim Term
Start Date (Study Day)/
End Date (Study Day)
XXXXXX
XXXXXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY (X)/
DDMMMYYYY (X)
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY (X)/
DDMMMYYYY (X)
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY (X)/
DDMMMYYYY (X)
XXXXXX
XXXXXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY (X)/
Ongoing
Abbreviations: BID = twice daily; MedDRA = Medical Dictionary for Regulatory Activities; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. Medical history was coded
using MedDRA version 23.0. Only subjects with medical history recorded are listed.
[1] Treatment received for both cohorts.
Programming note: SOC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 187 of 219
Listing 16.2.4.2.2
Chronic Hand Eczema Medical History
All Subjects
Cohort: Cohort x
Subject
Patch Tested
Anytime?
Date of Patch
Test (within past
3 years of
Baseline)/
Result
Distribution
Subject
ID
Treatment
[1]
Morphologic
Subtype of
Hand Eczema
Patch Test
Result
Surface of
Hand
Left Hand
Right Hand
XXXXX
X
XXXXXX
XXXXX
Yes
XXXXXX
DDMMMYYYY
/
Negative
Palmar [2]
XXXXXX
XXXXXX
Dorsal
XXXXXX
XXXXXX
Interdigital
XXXXXX
XXXXXX
Pulpitis
XXXXXX
XXXXXX
XXXXX
X
XXXXXX
XXXXX
Yes
XXXX:
XXX
DDMMMYYYY
/
Negative
Palmar [2]
XXXXXX
XXXXXX
Dorsal
XXXXXX
XXXXXX
Interdigital
XXXXXX
XXXXXX
Pulpitis
XXXXXX
XXXXXX
XXXXX
X
XXXXXX
XXXX
Yes
XXXXXX
DDMMMYYYY
/
Negative
Palmar [2]
XXXXXX
XXXXXX
Dorsal
XXXXXX
XXXXXX
Interdigital
XXXXXX
XXXXXX
Pulpitis
XXXXXX
XXXXXX
Abbreviations: BID = twice daily; QD = once daily.
[1] Treatment received for both cohorts.
[2] Including lateral aspects of fingers.
Programming note: If subject was patch tested anytime and the result is positive, concatenate the specify result “:” as shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 188 of 219
Listing 16.2.5.1
Study Drug Application at the Study Site
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Was Study
Drug
Application
Performed at
Study Site?
COVID-19
Caused Delay/
Missed IP
Application
Study
Visit
Date/Time of
Application (Study Day)
Pre-Application Tube Weight
(g)/
Post-Application Tube
Weight (g) Measurement
Applied
Dose (g)
Reason Pre-
and/or Post-
Application Tube
Weight
Measurement not
Performed
Kit/Lot Number/
Tube ID
XXXX
XXXXXX
Yes
Yes/
No
XXXX
DDMMMYYYY/HH:M
M (X)
XX
XX
XX/
XX
Yes/
No
XXXX
DDMMMYYYY/HH:M
M (X)
XX.X
XX.X
XX/
XX
No/
No
XXXX
DDMMMYYYY/HH:M
M (X)
XX
XX
XX/
XX
No:
XXXXXX
Yes/
Yes
XXXX
XXXX
XXXXXX
Yes
Yes/
No
XXXX
DDMMMYYYY/HH:M
M (X)
XX
XX
XX/
XX
Yes/
No
XXXX
DDMMMYYYY/HH:M
M (X)
XX
XX.X
XX/
XX
Yes/
No
XXXX
DDMMMYYYY/HH:M
M (X)
Not Done
XXXXXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
Programming note: If there is delay or missed IP application due to COVID-19, display as shown in the shell. Concatenate reason not done with “:” as shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 189 of 219
Listing 16.2.5.2
Study Drug Accountability
All Subjects
Cohort: Cohort x
Subject ID
Treatment
[1]
Lot/Kit Number/
Tube ID
Tube Dispensed?
Reason if No
Date Dispensed
(Study Day)
Dispense
Weight (g)
Tube Returned?
Reason if No
Date Returned
(Study Day)
Return
Weight (g)
XXXXX
XXXXXX
XXXXX/
XX
Yes
DDMMMYYYY (X)
XX.X
Yes
DDMMMYYYY (X)
XX.X
XXXXX/
XX
Yes
DDMMMYYYY (X)
XX.X
Yes
DDMMMYYYY (X)
XX.X
XXXXX/
XX
Yes
DDMMMYYYY (X)
ND
Yes
DDMMMYYYY (X)
ND
XXXXX
XXXXXX
XXXXX
No: XXXXX
No: XXXXX
Abbreviations: BID = twice daily; ND = not done; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
Programming note: Within subject, sort by dispense date, return date, lot number and Tube ID.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 190 of 219
Listing 16.2.5.3
Diary Dispensation
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Diary
Dispensation
Visit
Diary
Dispensed?
Date Dispensed
(Study Day)
Diary Returned
Visit
Diary Returned
and Reviewed?
Reason Diary
not Returned
Date Returned
(Study Day)
Date of Last Dose
XXXXX
XXXXXX
XXXXXX
Yes
DDMMMYYYY (X)
XXXXXX
Yes
DDMMMYYYY (X) DDMMMYYYY (X)
XXXXXX
Yes
DDMMMYYYY (X)
XXXXXX
Yes
DDMMMYYYY (X) DDMMMYYYY (X)
XXXXXX
Yes
DDMMMYYYY (X)
XXXXXX
No
XXXXXXXXXX
XXXXX
XXXXXX
XXXXX
No
XXXXXX
No
XXXXXXXXX
DDMMMYYYY (X)
Abbreviations: BID = twice daily; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 191 of 219
Listing 16.2.5.4
Compliance (CRF)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Study Visit [2]
Subject Compliant with
Medication? [2]
Non-Compliance due to
COVID-19? [2]
Date of Compliance Check
(Study Day) [2]
Compliance [2]
Overall Compliance
[3]
Was Subject Retrained if not
Compliant with Medication
[2]
XXXXXX
XXXXXX
XXXXXX
XXX
XXX
DDMMMYYYY (X)
XX.X %
XX.X %
XXXXXX
XXX
XX
DDMMMYYYY (X)
XX.X %
XXXXXX
XXX
XX
DDMMMYYYY (X)
XX.X %
XXXXXX
XXXXXX
XXXXXX
XXX
XXX
DDMMMYYYY (X)
XX.X %
XX.X%
XXXXXX
XXX
XX
DDMMMYYYY (X)
XX.X %
XXXXXX
XX
XX
XXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; CRF = case report form; IP = investigational product; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
[2] This data comes from CRF page and was only collected for subjects in Cohort 2.
[3] Overall compliance will be calculated based on number of applications divided by the expected number of IP applications for each subject. For BID dosing, the expected number of IP applications for each
subject is 30 (Cohort 1) or 170 (Cohort 2 BID) for subjects who completed the study or number of days between first and last application of IP, derived as 2 * (last treatment date - first treatment date + 1), for
subjects who discontinued early from the study. For QD dosing, the expected number of IP applications for each subject is 85 (Cohort 2 QD) for subjects who completed the study or number of days between
first and last application of IP, derived as (last treatment date - first treatment date + 1), for subjects who discontinued early from the study. Number of IP applications is calculated as number of expected IP
applications – missed IP applications as collected in the CRF.
Programming note: Populate overall compliance only for the first visit.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 192 of 219
Listing 16.2.5.5.1
Study Drug Interruption (QD)
All Subjects
Subject ID
Treatment [1]
Study Visit
Date of
Missed Dose (Study Day)
Missed Dose due to
COVID-19 Disruption?
Reason for Missed Dose
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY (X)
No
XXXXXXXXXXXXXX
XXXXXX
DDMMMYYYY (X)
No
XXXXXXXXXXXXXX
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY (X)
Yes
XXXXXXXXXXXXXX
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY (X)
No
XXXXXXXXXXXXXX
XXXXXX
DDMMMYYYY (X)
No
XXXXXXXXXXXXXX
Abbreviations: COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. Study Visit corresponds to the visit where the missed dose was
recorded in the case report form.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 193 of 219
Listing 16.2.5.5.2
Study Drug Interruption (BID)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Study Visit
Date/Time of
Missed Dose (Study Day)
Missed Dose
Timing
Missed Dose due to
COVID-19 Disruption?
Reason for Missed Dose
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY/HH:MM (X)
AM
No
XXXXXXXXXXXXXX
XXXXXX
DDMMMYYYY/HH:MM (X)
PM
No
XXXXXXXXXXXXXX
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY/HH:MM (X)
AM
Yes
XXXXXXXXXXXXXX
XXXXXX
XXXXXX
XXXXXX
DDMMMYYYY/HH:MM (X)
AM
No
XXXXXXXXXXXXXX
XXXXXX
DDMMMYYYY/HH:MM (X)
PM
No
XXXXXXXXXXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19.
Note: Study day is calculated relative to the date of first application of study drug. Study Visit corresponds to the visit where the missed dose was recorded in the case report
form.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 194 of 219
Listing 16.2.5.6.1
Cohort 1: Pharmacokinetic Sample Collection
PK Population
Cohort: Cohort x
Subject
ID
Treatment
[1]
Study Visit
PK
Collection
Time Point
PK Sample
Collected
Pre-Dose
PK Sample
collected?
Reason if No
If Assessment
Performed, COVID-19
Contributed to Delay in
Assessment
Date/Time of
Assessment
(Study Day)
Date/Time of Last
IP Application [2]
(Study Day)
Accession
Number
ARQ-252
Concentration
(unit)
XXXX
X
XXXXX
XXXXXX
XXXXXX
XXX
XXX
XXX
DDMMMYYY/
HH:MM (X)
DDMMMYYY/
HH:MM (X)
XXXXX
XX.X
XXXXXX
XXX
XXX
XXX
DDMMMYYY/
DDMMMYYY/
XXXXX
XX.X
XXXXXX
XXX
XXX
XXX
HH:MM (X)
HH:MM (X)
XXXXX
XX.X
XXXXXX
XX
XX: COVID-19
Disruption
XXX
XXXXXX
XX
XX: XXXXXX
XXX
Abbreviations: BID = twice daily; BLQ = Below the limit of quantification; COVID-19 = novel coronavirus disease-19; IP = investigational product; PK = pharmacokinetic; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for Cohort 1.
[2] Prior to the PK collection.
Programming note: Only cohort 1 subjects are presented in this listing. If the subject missed PK sample collection due to COVID or any other reason, concatenate reason not done as shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 195 of 219
Listing 16.2.5.6.2
Cohort 2: Pharmacokinetic Sample Collection
PK Population
(Same shell as Listing 16.2.5.6.2; use the below footnotes)
Abbreviations: BID = twice daily; BLQ = Below the limit of quantification; COVID-19 = novel coronavirus disease-19; IP = investigational product; PK = pharmacokinetic; QD = once
daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for Cohort 2.
Programming note: Only cohort 2 subjects are presented in this listing. If the subject missed PK sample collection due to COVID or any other reason, concatenate reason not done as
shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 196 of 219
Listing 16.2.5.7
Cohort 1: Pharmacokinetic Calculated Parameters
PK Population
Subject ID
Treatment [1]
Study Visit
Analyte
AUC0-t
(unit)
Tmax
(unit)
Cmax
(unit)
XXXXX
XXXXXX
XXXXXX
XXXXXX
XX
XX
XX
XXXXXX
XX
XX
XX
XXXXXX
XX
XX
XX
XXXXXX
XXXXXX
XX
XX
XX
Abbreviations: BID = twice daily; PK = pharmacokinetic.
[1] Treatment received.
Programming note: The above parameters are expected. However the final parameters provided by the pharmacokineticist will be listed and
may be different than shown.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 197 of 219
Listing 16.2.6.1
Investigator Global Assessment (IGA)
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
Was Assessment
Completed?
Study Visit
Date of
Assessment
(Study Day)
Result
Text Result
Change from
Baseline
IGA Score of
“Clear” or
“Almost Clear”
[2]
IGA Success
[3]
XXXX
XXXXXX
Yes
XXXX
DDMMMYYYY (X)
X
XXXXXX
Yes
XXXX
DDMMMYYYY (X)
X
XXXXXX
X
No
No
Yes: COVID-19
Disruption
Caused/Contributed to
Delay in IGA Collection
XXXX
DDMMMYYYY (X)
X
XXXXXX
X
No
No
Yes
XXXX
DDMMMYYYY (X)
X
XXXXXX
X
Yes
Yes
XXXX
XXXXXX
No: COVID-19
Disruption
Caused/Contributed to
Missed IGA Collection
XXXX
DDMMMYYYY (X)
X
XXXXXX
No: XXXXXXXX
XXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
Change from baseline is calculated as result – baseline result.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] IGA Score of “Clear” or “Almost Clear” (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear”; “No” otherwise.
[3] IGA Success (“Yes”) is defined as an IGA score of “Clear” or “Almost Clear” plus a ≥2-grade improvement from baseline; “No” otherwise.
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or contribute to a delay in IGA Collection?” is “Yes”,
then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in IGA Collection”; if answer to COVID-19 question is “No”, only display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed IGA Collection?” is “Yes”, then display
“No: COVID-19 Disruption Caused/Contributed to Missed IGA Collection”; if reason IGA not completed is non-missing, concatenate that reason with the response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed IGA Collection; XXXXXXXXXX”
“No: XXXXXXXXXXXX’


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 198 of 219
Listing 16.2.6.2
Worst Itch Numerical Rating Scale (WI-NRS)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Was Assessment
Completed?
Study Week
Date of
Assessment
(Study Day)
Result
Change
from
Baseline
WI-NRS
Success
(Baseline ≥4)
[2]
XXXXXX
XXXXXX
Yes
Baseline
DDMMMYYYY (-1)
X
Yes
Week 1
DDMMMYYYY (1)
X
X
Yes
DDMMMYYYY (2)
X
X
Yes
DDMMMYYYY (3)
X
X
Yes
DDMMMYYYY (4)
X
X
Yes
DDMMMYYYY (5)
X
X
Yes
DDMMMYYYY (6)
X
X
Yes
DDMMMYYYY (7)
X
X
…
Yes
Week 2
DDMMMYYYY (14)
X
X
Average Weekly Score: X [3]
X
Yes
Yes
Week X
DDMMMYYYY (X)
X
X
No: COVID-19
Disruption
DDMMMYYYY (X)
X
X
XXXXXX
XXXXXX
Yes
XXXX
DDMMMYYYY (X)
X
No: XXXXXX
XXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily; WI-NRS = Worst Itch – Numeric Rating Scale.
Note: Study day is calculated relative to the date of first application of study drug. Subjects rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10
(worst itch imaginable). Higher score indicates greater itch intensity. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
Change from baseline is calculated as result – baseline result.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] WI-NRS Success is defined as achievement of a 4-point reduction in WI-NRS pruritus score at each study week compared to baseline, calculated only for subjects with a
pruritus score of ≥4 at baseline.
[3] Average of the WI-NRS pruritus daily diary scores for each study week. If at least 1 WI-NRS pruritus score in present in this time period, the average weekly WI-NRS pruritus
score was calculated.
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or contribute to a missed WI-NRS
Collection?” is “Yes”, then only display “Yes”.
For “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed WI-NRS Collection?” is “Yes”,
then display “No: COVID-19 Disruption Caused/Contributed to Missed WI-NRS Collection”; if reason WI-NRS not completed is non-missing, concatenate that reason with the
response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed WI-NRS Collection; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 199 of 219
Listing 16.2.6.3
Hand Eczema Severity Index (HECSI)
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Was
Assessment
Completed?
Study Visit
Date of
Assessment
(Study Day)
Location
Clinical Signs
Numeric
Result
Text
Result
Change
from
Baseline
% Change
from
Baseline
XXXX
XXXXXX
Yes
XXXXXXX
DDMMMYYY
Y (XX)
Fingertips
Affected Area
XX
XXXX
X
Erythema
XX
XXXX
X
Infiltration/papulation
XX
XXXX
X
Vesicles
XX
XXXX
X
Fissures
XX
XXXX
X
Scale
XX
XXXX
X
Oedema
XX
XXXX
X
Fingertips Subscore [2]
XX
Fingers (except tips)
Affected Area
XX
XXXX
X
…
XX
XXXX
X
Fingers (except tips) Subscore
[2]
XX
Palm of Hands
Affected Area
XX
XXXX
X
…
XX
XXXX
X
Palm of Hands Subscore [2]
XX
Back of Hands
Affected Area
XX
XXXX
X
…
XX
XXXX
X
Back of Hands Subscore [2]
XX
Wrists
Affected Area
XX
XXXX
X
…
XX
XXXX
X
Wrists Subscore [2]
XX
Total Score [3]
XX


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 200 of 219
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; HECSI = Hand Eczema Severity Index; QD = once daily.
Note: Study day is calculated relative to the date of the first application of study drug. The HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the
extent of the lesions on each of 5 hand areas by use of standard scales. Baseline is the last non-missing measurement taken on or before the day of first application of study drug. Change from
baseline is calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] Subscores are calculated as the sum of erythema, infiltration/papulation, vesicles, fissures, scale, and oedema, respectively, scored on a scale of 0 to 3 (none to severe) time is estimated area of
skin involved, graded on a scale of 0 to 4, within a location. The range for each subscore is 0 to 72. Lower scores indicate better outcomes.
[3] The total score is calculated as the sum of all subscores. The range for the total score is 0 to 360. Lower scores indicate better outcomes.
Programming note: Continue for all visits. Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or
contribute to a delay in HECSI Collection?” is “Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in HECSI Collection”; if answer to COVID-19 question is “No”, only
display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed HECSI Collection?” is “Yes”, then
display “No: COVID-19 Disruption Caused/Contributed to Missed HECSI Collection”; if reason HECSI not completed is non-missing, concatenate that reason with the response to “No”, as
follows:
“No: COVID-19 Disruption Caused/Contributed to Missed HECSI Collection; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 201 of 219
Listing 16.2.6.4
Pain Numeric Rating Scale (NRS)
All Subjects
(Same shell as Listing 16.2.6.2; change all instances of WI-NRS to Pain NRS; use the below footnotes)
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; NRS = Numeric Rating Scale; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. Subjects rate the worst pain intensity on an 11-point scale ranging from 0 (no pain) to 10
(worst possible pain). Higher score indicates greater pain intensity. Baseline is the last non-missing measurement taken on or before the day of first application of study drug.
Change from baseline is calculated as result – baseline result.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] Pain NRS success is defined as 4-point reduction in Pain NRS score at Weeks 2, 4, 8, or 12 compared to baseline, calculated only for subjects with a Pain NRS score of
≥4 at baseline.
[3] Average of the Pain NRS daily diary scores for each study week. If at least 1 Pain NRS score in present in this time period, the average weekly Pain NRS score was calculated.
Programming note: For “Was Assessment Completed?” column, if answer is Yes, then only display “Yes”.
For “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed NRS Collection?” is “Yes”,
then display “No: COVID-19 Disruption Caused/Contributed to Missed Pain NRS Collection”; if reason WI-NRS not completed is non-missing, concatenate that reason with the
response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed Pain NRS Collection; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 202 of 219
Listing 16.2.6.5
Quality of Life in Hand Eczema Questionnaire (QOLHEQ)
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Was
Assessment
Completed?
Study Visit
Date of
Assessment
(Study Day)
Question [2]
Result
Text Result
Change
from
Baseline
XXXX
XXXXXX
Yes
XXXX
DDMMMYYYY/
(XX)
1. Being painful
0
Never
2. Restricting/impairing me in my job
1
Rarely
3. Restricting/impairing me in doing
everyday home duties
2
Sometimes
4. Because I have to wear gloves
3
Often
5. Making me feel frustrated
0
All the time
6. Itching
1
Several days
7. Because treatment is time consuming
2
More than half the days
----
30. making me feel nervous
3
Nearly every day
Symptoms Subscore [3]
XX
Emotions Subscore [4]
XX
Limitations in Functioning Subscore [5]
XX
Treatment and Prevention Subscore [6]
XX
Total Score [7]
XX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily; QOLHEQ = Quality of Life in Hand Eczema Questionnaire.
Note: Study day is calculated relative to the date of the first application of study drug. Baseline is the last non-missing measurement taken on or before the day of first application of study
drug. Change from baseline is calculated as result – baseline result.
[1] Randomized treatment for Cohort 2.
[2] These questions are based on the “Over the last 7 days, how often have you been bothered by any of the skin conditions of my hand?” prompt.
[3] The range for Symptoms subscore is 0 to 27, where lower scores indicate better outcomes.
[4] The range for Emotions subscore is 0 to 31, where lower scores indicate better outcomes.
[5] The range for Limitations in Functioning subscore is 0 to 32, where lower scores indicate better outcomes.
[6] The range for Treatment and Prevention subscore is 0 to 27, where lower scores indicate better outcomes
[7] The QOLHEQ total score is calculated as sum of all 30 questions. The range for Total score is 0 to 117, where lower scores indicate better outcomes.
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “If Yes, did COVID-19 disruption cause or contribute to a delay in QOLHEQ
Collection?” is “Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in QOLHEQ Collection”; similarly, if the answer to the question “If Yes, did QOLHEQ
assessment occur via telemedicine?” is “Yes”, set to “Yes: QOLHEQ assessment occurred via telemedicine”; if both are answered “Yes” concatenate them with a semicolon; if answers to
both COVID-19 questions are “No”, only display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed QOLHEQ Collection?” is
“Yes”, then display “No: COVID-19 Disruption Caused/Contributed to Missed QOLHEQ Collection”; if reason QOLHEQ not completed is non-missing, concatenate that reason with the
response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed QOLHEQ Collection; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 203 of 219
Listing 16.2.6.6
% Body Surface Area (BSA)
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
Was
Assessment
Performed?
Study Visit
Date of
Assessment
(Study Day)
Surface of Hand
Result
Change from
Baseline
% Change from
Baseline
XXXX
XXXXXX
XXX
XXXX
DDMMMYYYY
(XX)
Dorsal % BSA (Left Hand)
XX %
Dorsal % BSA (Right Hand)
XX %
Palmar % BSA (Left Hand)
XX %
Palmar % BSA (Right Hand)
XX.X %
Total Hand % BSA [2]
XX.X %
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of the first application of study drug. Baseline is the last non-missing measurement taken on or before the day of first application of study
drug. Change from baseline is calculated as result – baseline result. Percent change from baseline is calculated as (change from baseline/baseline)*100.
[1] Treatment received for Cohort 1 and randomized treatment for Cohort 2.
[2] Total Hand % BSA is calculated as the sum of dorsal % BSA (left hand), dorsal % BSA (right hand), palmar % BSA (left hand), and palmar % BSA (right hand).
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or contribute to a delay in BSA Collection?” is “Yes”,
then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in BSA Collection”; if answer to COVID-19 question is “No”, only display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed BSA Collection?” is “Yes”, then display
“No: COVID-19 Disruption Caused/Contributed to Missed BSA Collection”; if reason BSA not completed is non-missing, concatenate that reason with the response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed BSA Collection; XXXXXXXXXX”
“No: XXXXXXXXXXXX’


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 204 of 219
Listing 16.2.6.7
Nail Dystrophy Assessment
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
Was
Assessment
Performed?
Study Visit
Date of Assessment
(Study Day)
Subject has at least
One Nail with
Significant
Dystrophy
If Yes, Is there
Normal
Appearing
Nail Distal to
the Cuticle
Result (mm)
XXXX
XXXXXX
XXX
XXXX
DDMMMYYYY
(XX)
Yes: Left
XXXX
DDMMMYYYY
(XX)
Yes
XX
XXXX
DDMMMYYYY
(XX)
Yes
XX
XXXX
DDMMMYYYY
(XX)
No
XXXX
XXXXXX
XXX
XXXX
DDMMMYYYY
(XX)
No
XXXX
XXXXXX
No:
XXXXXXX
XXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of the first application of study drug.
[1] Randomized treatment for Cohort 2.
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or
contribute to a delay in Nail Dystrophy Assessment?” is “Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in Nail
Dystrophy Assessment”; if answer to COVID-19 question is “No”, only display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to
missed Nail Dystrophy Assessment?” is “Yes”, then display “No: COVID-19 Disruption Caused/Contributed to Missed Nail Dystrophy Assessment”;
if reason Nail Dystrophy Assessment not completed is non-missing, concatenate that reason with the response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed Nail Dystrophy Assessment; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 205 of 219
Listing 16.2.7.1
Adverse Events
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
TEAE?
System Organ Class/
Preferred Term/
Verbatim Term
Start Date/Time (Study Day)/
End Date/Time (Study Day)
CTCAE Toxicity Grade/
Relationship
Outcome/
Action Taken/
Other Action Taken
Serious?
AE Lead to Study
D/C?
XXXXX
XXXXXX
XXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXXX
XXXXXXXXXX
DDMMMYYYY/hh:mm (X)/
DDMMMYYYY/ hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XX
XX
XXXXX
XXXXXX
XXX
XXXXXXXXXXXXXX/
XXXXXXXXXXXX
XXXXXXXXXXXXX
DDMMMYYYY/ hh:mm (X)/
DDMONYYYY/ hh:mm (X)
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XX
XX
XX
XXXXXXXXXXXXXX/
XXXXXXXXXXXXX
XXXXXXXXXXXXX
DDMONYYYY/ hh:mm (X)/
Ongoing
XXXXXXXXX/
XXXXXXXXXX
XXXXXXXXX/
XXXXXXXXXX/
XXXXXXXXXX
XXX
XXX
Abbreviations: BID = twice daily; CTCAE = Common Terminology Criteria for Adverse Events; D/C = discontinuation; MedDRA = Medical Dictionary for Regulatory Activities;
QD = once daily; TEAE = treatment emergent adverse event.
Note: Study day is calculated relative to the date of first application of study drug. AEs were coded using MedDRA version 23.0. All AEs with an onset on or after the day of study treatment
through study completion are considered as TEAEs.
[1] Treatment received for both cohorts.
Programming note: If time missing, display “- -:- -”. “Other Action Taken” will be either None, Concomitant Medication, Non-drug Therapy, Hospitalization or Prolongation of Hospitalization,
Discontinued Study or Other; if specify text is needed, concatenate “Concomitant Medication:” or “Other:” with the text. If no events meet the criteria for display, present “No events are reported.”
SOC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 206 of 219
Listing 16.2.8.1.1
Clinical Laboratory Data: Clinical Chemistry
All Subjects
Cohort: Cohort x
Subject
ID
Study
Visit
Date/Time of
Assessment
(Study Day)
Standard
Results
Reference
Range
[2]
Treatment
[1]
Parameter (unit)
Reference
Range
Flag
Result
Interpretation;
Specify CS
Finding
Accession
Number
Comments/
Reason not Done
XXXXX
XXXXX
Alanine
Aminotransferase (U/L)
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
High
Normal
XXXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
Abnormal, NCS
XXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
Low
Normal
XXXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
Normal
XXXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
Abnormal, CS;
XXXXXXX
XXXXX
Alkaline
Phosphatase (U/L)
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
Low
XXXXX
XXXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
XXXXX
XXXXX
XXXXX
ND
XXXXXXX
XXXXX
DDMMMYYYY/hh:mm
(XX)
XX
XX – YY
High
XXXXXX
XXXXX
Abbreviations: BID = twice daily; CS = clinically significant; NCS = not clinically significant; ND = not done; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. Time is collected in the ACM data.
[1] Treatment received for both cohorts.
[2] Reference range is used to identify potentially clinically significant laboratory values.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 207 of 219
Listing 16.2.8.1.2
Clinical Laboratory Data: Hematology
All Subjects
(Same shell as Listing 16.2.8.1.1)
Listing 16.2.8.1.3
Clinical Laboratory Data: Urinalysis
All Subjects
(Same shell as Listing 16.2.8.1.1)
Listing 16.2.8.1.4
Clinical Laboratory Data: TSH/T4
All Subjects
(Same shell as Listing 16.2.8.1.1)


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 208 of 219
Listing 16.2.8.1.5
Clinical Laboratory Data: Serum and Urine Pregnancy Test
Female Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Was Pregnancy Test
Performed? Reason if
No
Study Visit
Type of Test
Date/Time Performed
(Study Day)
Result
XXXXX
XXXXXX
Yes
XXXXXX
Serum
DDMMMYYYY (XX)
XXXXXXXX
Urine
DDMMMYYYY/hh:mm (XX) XXXXXXXXX
XXXXXX
Urine
DDMMMYYYY/hh:mm (XX) XXXXXXXXX
XXXXX
XXXXXX
Yes
XXXXXX
Serum
DDMMMYYYY (XX)
XXXXXXXXX
No:
XXXXXXXXXX
XXXXXX
Urine
Abbreviations: BID = twice daily; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
Programming note: If time is missing, display it as --:--.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 209 of 219
Listing 16.2.8.1.6
Follicle Stimulating Hormone Test
Female Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Was Assessment
Performed? Reason if
No
Study Visit
Date of Assessment
(Study Day)
Result
XXXXX
XXXXXX
Yes
XXXXXX
DDMMMYYYY (XX)
XXXXX
DDMMMYYYY (XX)
XXXXX
XXXXXX
DDMMMYYYY (XX)
XXXXX
XXXXX
XXXXXX
Yes
XXXXXX
DDMMMYYYY (XX)
XXXXX
No:
XXXXXXXXXX
XXXXXX
Abbreviations: BID = twice daily; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 210 of 219
Listing 16.2.9.1
Investigator Local Tolerability Assessments
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Tolerability
Assessment Performed?
Study Visit
Date/Time of Assessment
(Study Day)
Dermal Response
Other Effects
XXXXX
X
XXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
XXXXX
X
XXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
XXXXX
X
XXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
X = XXXXXXXXX
X = XXXXXXXXX
No: COVID-19
Disruption
XXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; IP = investigational product; QD = once daily.
Note: Study day is calculated relative to the date of the first application of study drug. This assessment will be conducted by the investigator prior to the application of IP in
the study site.
[1] Treatment received for both cohorts.
Programming note: For “Tolerability Assessment Performed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or contribute to a
delay in assessment collection?” is “Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in Assessment Collection”; if answer to COVID-19
question is “No”, only display “Yes”.
Similarly, for “Tolerability Assessment Performed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed
assessment collection?” is “Yes”, then display “No: COVID-19 Disruption Caused/Contributed to Missed Assessment Collection”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 211 of 219
Listing 16.2.9.2
Subject Local Tolerability Assessments
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Tolerability
Assessment
Performed?
Study Visit
Date/Time of Assessment
(Study Day)
Grade
Sensation Following the Application of IP
XXXXX
X
XXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
0 = None
No sensation
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
1 = Mild
Slight warm, tingling sensation; not really bothersome
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
2 = Moderate
Definite warm, tingling sensation that is somewhat
bothersome
XXXXX
X
XXXXXX
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
0 = None
No sensation
Yes
XXXXXX
DDMMMYYYY/hh:mm
(XX)
3 = Severe
Hot tingling/stinging sensation that has caused definite
discomfort
No: COVID-19
Disruption
XXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; IP = investigational product; QD = once daily.
Note: Study day is calculated relative to the date of the first application of study drug. This assessment was performed at baseline visit 10 to 15 minutes after the application of IP in the
study site.
[1] Treatment received for both cohorts.
Programming note: For “Tolerability Assessment Performed?” column, if answer is Yes and answer to question “If Yes, did COVID-19 disruption cause or contribute to a delay in
assessment collection?” is “Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in Assessment Collection”; similarly, if the answer to the question “If Yes, did
assessment occur via telemedicine?” is “Yes”, set to “Yes: Assessment occurred via telemedicine”; if both are answered “Yes” concatenate them with a semicolon; if answers to both
COVID-19 questions are “No”, only display “Yes”.
Similarly, for “Tolerability Assessment Performed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed assessment
collection?” is “Yes”, then display “No: COVID-19 Disruption Caused/Contributed to Missed Assessment Collection”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 212 of 219
Listing 16.2.9.3
Vital Signs
All Subjects
Cohort: Cohort x
Subject
ID
Treatment
[1]
Vital Signs
Collected?
Reason if
No
Study
Visit
Date of
Assessment
(Study Day)
Temp
(°C)
Heart
Rate
(bpm)
Position
Blood
Pressure (mmHg)
Height
(cm)
Abnormal Findings/
Systolic
Diastolic
Weight
(kg)
BMI
(kg/m2)
Clinically Significant/
Description of Finding
XXXX
XXXX
Yes
XXXXX
DDMMMYYYY
(X)
XX.X
XX
XXXX
XX
XX
XXX
XX.X
XX.X
XX
Yes
XXXXX
DDMMMYYYY
(X)
XX.X
XX
XXXXX
XX
XX
XX.X
No:
XXXXXX
XXXXX
Yes
XXXXX
DDMMMYYYY
(X)
XX.X
XX
XXXXX
XX
XX
XX.X
XX.X
XXX/
XXX/
XXXXXXX
Abbreviations: BID = twice daily; BMI = body mass index; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
[2] BMI is derived as (weight in kg)/[(height in cm/100)2].


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 213 of 219
Listing 16.2.9.4
12-Lead Electrocardiogram (ECG)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
ECG
Performed?
Reason if No
Study
Visit
Date/Time of
Assessment
(Study Day)
Heart Rate
(beats/min)
PR
(msec)
QRS
Interval
(msec)
QT
Interval
(msec)
QTcF
(msec)
Findings/
Comments
XXXX
XXXX
Yes
XXXXX
DDMMMYYYY/
hh:mm (X)
XX.X
XX
XXXX
XXX
XX.X
XX
Yes
XXXXX
DDMMMYYYY/
hh:mm (X)
XX.X
XX
XXXXX
XX.X
No: XXXXXX
XXXXX
Yes
XXXXX
DDMMMYYYY/
hh:mm (X)
XX.X
XX
XXXXX
XX.X
XXX/
XXXXXXX
Abbreviations: BID = twice daily; CS = clinically significant; ECG = electrocardiogram; NCS = not clinically significant; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 214 of 219
Listing 16.2.9.5
Physical Examination
All Subjects
Cohort: Cohort x
Physical
Examination
Date of
Subject ID
Treatment [1]
Performed?
Reason if No
Study Visit
Assessment (Study
Day)
Body System
Result
Abnormal Findings
Clinically Significant?
XXXXXX
XXXXXXX
Yes
XXXXXXX
DDMMMYYYY
(-X)
Skin
Normal
Lungs
Abnormal
XXXXXXXX
No
Heart
Normal
Yes
XXXXXXX
DDMMMYYYY
(-X)
Skin
Normal
Lungs
Abnormal
XXXXXXXX
No
Heart
Normal
No: XXXXXXX
XXXXXXX
Abbreviations: BID = twice daily; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
Programming note: Concatenate reason not done as shown in the shell.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 215 of 219
Listing 16.2.9.6
Medical Photography
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Photography Performed?
Study Visit
Date of Assessment
(Study Day)
XXXXXX
XXXXXX
Yes
XXXXXX
DDMMMYYYY (XX)
Yes
XXXXXX
DDMMMYYYY (XX)
Yes
XXXXXX
DDMMMYYYY (XX)
Yes
XXXXXX
DDMMMYYYY (XX)
No: XXXXXX
XXXXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
Programming note: For “Photography Performed?” column, if answer is Yes and answer to question “Yes, did COVID-19
disruption cause or contribute to a delay in assessment collection?” is “Yes”, then display “Yes: COVID-19 Disruption
Caused/Contributed to Delay in Assessment Collection”; if answer to COVID-19 question is “No”, only display “Yes”.
Similarly, for “Photography Performed?” column, if answer is No and answer to question “If No, and Photograph consent given
please specify reason photographs not collected” is “COVID-19 Disruption”, then display “No: COVID-19 Disruption
Caused/Contributed to Missed Assessment Collection”; if reason assessment collection not completed is non-missing, concatenate
that reason with the response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed Assessment Collection; XXXXXXXXXX” or “No: XXXXXXXXXXXX”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 216 of 219
Listing 16.2.9.7
Prior and Concomitant Medications
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Prior/
Concomitant
[2]
Indication
ATC Class (Level 4)/
Preferred Term/
Verbatim Term
Start Date (Study Day)/
End Date (Study Day)
Dose (unit)
Route/
Frequency
XXXXXX
XXXXXX
Prior
XXXXXXXX
XXXXXXXXXXXXXXXXX/
XXXXXXXXXXXXXX/
XXXXXXXXXXXXX
DDMMMYYYY (X)/
DDMMMYYYY (X)
XXX (XXX)
XXXXXXXX/
XXXXXXX
Both
XXXXXXXX
XXXXXXXXX/
XXXXXXXXXXXXXXX/
XXXXXXXXXXX
DDMMMYYYY (X)/
Ongoing
XXX (XXX)
XXXXXXXX/
XXXXXXX
Concomitant
XXXXXXX
XXXXXXXXX/
XXXXXXXXXXXXXX/
XXXXXXXXXXXXX
DDMMMYYYY (X)/
DDMMMYYYY (X)
XXX (XXX)
XXXXXXXX/
XXXXXXX
Abbreviations: ATC = anatomic therapeutic chemical; BID = twice daily; NA = Not applicable; QD = once daily; WHO-DDE = World Health Organization-Drug Dictionary
Enhanced.
Note: Study day is calculated relative to the date of first application of study drug. Medications were coded using WHO-DDE Global B3 version September 2019.
[1] Treatment received in both cohorts.
[2] Prior indicates medication that was started and stopped prior to dosing of study drug. Concomitant indicates medication that started during the treatment period. Both
indicates medication that was started prior to dosing of study drug and continued during the treatment period.
Programming note: If Dose unit, Route or Frequency is Other, display other specify text only (i.e., do not display “Other: XXXXXX” but just “XXXXXX “). Sort by subject, start date, end date,
ATC level 4 & PT. ATC & PT text should be presented as is from the dataset.


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 217 of 219
Listing 16.2.9.8.1
Hand Washing/Hand Sanitizer Use (QD Dosing)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Cleansing Performed?
[2]
Study Visit
Date of Cleansing
(Study Day)
Type of Hand Cleansing
Time of First Hand Cleansing
Post Study Drug
Application
XXXXXX
XXXXXX
Yes
XXXXXX
DDMMMYYYY (XX)
Hand Washing
XXXXXXXX
DDMMMYYYY (XX)
Hand Washing
XXXXXXXX
DDMMMYYYY (XX)
Hand Sanitizer
XXXXXXXX
XXXXXX
DDMMMYYYY (XX)
Hand Sanitizer
XXXXXXXX
No
XXXXXX
Abbreviations: QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
[2] This question is based on the prompt “did any handwashing or hand sanitizer use occur within 4 hours of study drug application since last visit?”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
|
AD-PR-109.02 Effective date: 17-Aug-2020
Page 218 of 219
Listing 16.2.9.8.2
Hand Washing/Hand Sanitizer Use (BID Dosing)
All Subjects
Cohort: Cohort x
Subject ID
Treatment [1]
Cleansing
Performed?
Study Visit
Date of Cleansing
(Study Day)
AM/PM Dose
Type of Hand Cleansing
Time of First Hand Cleansing
Post Study Drug
Application
XXXXXX
XXXXXX
XXX
XXXXXX
DDMMMYYYY (XX)
XX
Hand Washing
XXXXXXXX
DDMMMYYYY (XX)
XX
Hand Washing
XXXXXXXX
DDMMMYYYY (XX)
XX
Hand Sanitizer
XXXXXXXX
XXXXXX
DDMMMYYYY (XX)
XX
Hand Sanitizer
XXXXXXXX
DDMMMYYYY (XX)
XX
Hand Sanitizer
XXXXXXXX
Abbreviations: BID = twice daily.
Note: Study day is calculated relative to the date of first application of study drug.
[1] Treatment received for both cohorts.
[2] This question is based on the prompt “did any handwashing or hand sanitizer use occur within 4 hours of study drug application since last visit?”


Statistical Analysis Plan,
Sponsor Arcutis Biotherapeutics, Inc.
Protocol Number ARQ-252-205
PCN Number ARCU211360
AD-ST-33.06 Effective date: 12-Nov-2020
Version Final 1.0
|
Date 09-Apr-2021
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AD-PR-109.02 Effective date: 17-Aug-2020
Page 219 of 219
Listing 16.2.9.9
Modified Total Lesion Symptom Score (mTLSS)
All Subjects
Cohort: Cohort x
Subject
ID
Treatment [1]
Was Assessment Completed?
Study Visit
Date of
Assessment
(Study Day)
Item
Result
XXXX
XXXXXX
Yes: COVID-19 Disruption Caused/Contributed
to Delay in mTLSS Collection
XXXX
DDMMMYYYY (X)
Erythema
X = XXXXXXXXXXX
Scaling
X = XXXXXXXXXXX
Lichenification/hyperkeratosis
X = XXXXXXXXXXX
Vesiculation
X = XXXXXXXXXXX
Edema
X = XXXXXXXXXXX
Fissures
X = XXXXXXXXXXX
Pruritus/Pain
X = XXXXXXXXXXX
Yes
XXXX
DDMMMYYYY (X)
Erythema
X = XXXXXXXXXXX
…
XXXX
XXXXXX
No: COVID-19 Disruption Caused/Contributed
to Missed mTLSS Collection
XXXX
DDMMMYYYY (X)
No: XXXXXXXX
XXXX
Abbreviations: BID = twice daily; COVID-19 = novel coronavirus disease-19; QD = once daily.
Note: Study day is calculated relative to the date of first application of study drug. The mTLSS was removed from the protocol as of amendment 1 (11May2020), thus not all subjects and visits
will be present.
[1] Treatment received for both cohorts.
Programming note: For “Was Assessment Completed?” column, if answer is Yes and answer to question “Yes, did COVID-19 disruption cause or contribute to a delay in mTLSS Collection?” is
“Yes”, then display “Yes: COVID-19 Disruption Caused/Contributed to Delay in mTLSS Collection”; if answer to COVID-19 question is “No”, only display “Yes”.
Similarly, for “Was Assessment Completed?” column, if answer is No and answer to question “If No, did COVID-19 disruption cause or contribute to missed mTLSS Collection?” is “Yes”, then display
“No: COVID-19 Disruption Caused/Contributed to Missed mTLSS Collection”; if reason mTLSS not completed is non-missing, concatenate that reason with the response to “No”, as follows:
“No: COVID-19 Disruption Caused/Contributed to Missed mTLSS Collection; XXXXXXXXXX”
“No: XXXXXXXXXXXX’