Clinical trial NCT05028582
Conditions: Scalp Psoriasis
Sponsor: Arcutis Biotherapeutics, Inc.
Start date: 2021-08-24; Completion date: 2022-06-03
Enrollment: 432 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This was a parallel group, double blind, vehicle-controlled study to assess the safety and efficacy of roflumilast (ARQ-154) 0.3% foam vs vehicle foam applied once daily (qd) for 8 weeks by participants with plaque psoriasis of the scalp and body.

Detailed description:

Arms: arm 1: Participants with plaque psoriasis of the scalp and body applied roflumilast foam 0.3% once daily (qd) for 8 weeks. arm 2: Participants with plaque psoriasis of the scalp and body applied vehicle foam qd for 8 weeks.
Interventions: intervention 1: Roflumilast Foam 0.3% intervention 2: Vehicle Foam
Intervention descriptions: intervention 1: Roflumilast foam 0.3% intervention 2: Vehicle foam matched to roflumilast 0.3% foam.

Protocol documents:
Prot_000.pdf: 


Protocol ARQ-154-309 
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SITE INVESTIGATOR SIGNATURE PAGE 
 
ARQ-154-309 
A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study of the Safety and 
Efficacy of ARQ-154 Foam 0.3% Administered QD in Subjects with Scalp and Body Psoriasis 
 
SPONSOR: 
Arcutis Biotherapeutics, Inc. 
3027 Townsgate Road, Suite 300 
Westlake Village, CA 91361 
 
ISSUE DATE: 
12 MAY 2022 
 
 
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-154 foam 0.3% 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. 




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TABLE OF CONTENTS 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
1.1. 
Synopsis ......................................................................................................................11 
1.2. 
Study Schema .............................................................................................................19 
1.3. 
Schedule of Visits and Assessments ...........................................................................20 
2. 
BACKGROUND AND RATIONALE .......................................................................22 
2.1. 
Introduction .................................................................................................................22 
2.2. 
Conclusions on Toxicity Findings ..............................................................................23 
2.3. 
Clinical Studies ...........................................................................................................24 
2.3.1. 
Scalp and Body Psoriasis Phase 2b ............................................................................24 
2.4. 
Rationale for Development .........................................................................................25 
2.4.1. 
Dose Selection ............................................................................................................25 
2.4.2. 
Risks and/or Benefits to Subjects ...............................................................................25 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................26 
3.1. 
Study Objectives .........................................................................................................26 
3.1.1. 
Primary Objective .......................................................................................................26 
3.2. 
Study Endpoints ..........................................................................................................26 
3.2.1. 
Co-Primary Endpoints ................................................................................................26 
3.2.2. 
Secondary Endpoints ..................................................................................................26 
4. 
INVESTIGATIONAL PLAN .....................................................................................27 
4.1. 
Overall Study Design and Plan ...................................................................................27 
4.2. 
Number of Sites and Subjects .....................................................................................27 
4.3. 
Subject Participation ...................................................................................................27 
4.4. 
Subject Identification Number Assignment ................................................................27 
4.5. 
Selection of Study Population ....................................................................................28 
4.5.1. 
Inclusion Criteria ........................................................................................................28 
4.5.2. 
Exclusion Criteria .......................................................................................................29 
4.6. 
Randomization ............................................................................................................30 
4.7. 
Prohibitions and Concomitant Therapy ......................................................................31 
4.8. 
Treatment ....................................................................................................................32 
4.8.1. 
IP Supplies, Packaging, and Labeling ........................................................................32 


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4.8.2. 
Treatment Administration ...........................................................................................33 
4.8.3. 
Treatment Compliance ................................................................................................33 
4.8.4. 
Blinding ......................................................................................................................34 
4.8.5. 
Breaking Treatment Codes .........................................................................................34 
4.8.6. 
Removal of Subjects from Investigational Product ....................................................34 
4.8.7. 
Removal of Subjects from the Study ..........................................................................35 
5. 
STUDY PROCEDURES ............................................................................................35 
5.1. 
Safety Assessments .....................................................................................................35 
5.1.1. 
Screening ....................................................................................................................36 
5.1.2. 
Contraception Requirements ......................................................................................37 
5.1.3. 
Baseline .......................................................................................................................37 
5.1.4. 
Physical Examination .................................................................................................37 
5.1.5. 
Vital Signs, Height and Weight ..................................................................................38 
5.1.6. 
Laboratory Tests .........................................................................................................38 
5.1.7. 
Patient Health Questionnaire Depression Scale (PHQ-8) ..........................................39 
5.1.8. 
Patient Health Questionnaire Depression Scale (Modified PHQ-A) ..........................40 
5.1.9. 
Columbia-Suicide Severity Rating Scale (C-SSRS) ...................................................40 
5.1.10. 
Local Tolerability Assessment ...................................................................................41 
5.1.11. 
Adverse Events ...........................................................................................................42 
5.2. 
Efficacy Evaluations ...................................................................................................42 
5.2.1. 
Scalp (S-IGA) and Body (B-IGA) Investigator Global Assessments ........................42 
5.2.1.1. 
Scalp - Investigator Global Assessment of Disease (S-IGA) .....................................43 
5.2.1.2. 
Body - Investigator Global Assessment of Disease (B-IGA, i.e. non-scalp) .............44 
5.2.2. 
Extent of Scalp Involvement ......................................................................................44 
5.2.3. 
Body Surface Area (BSA) ..........................................................................................44 
5.2.4. 
Psoriasis Scalp Severity Index (PSSI) ........................................................................45 
5.2.5. 
Psoriasis Area and Severity Index (PASI) ..................................................................45 
5.2.6. 
Scalp Itch-NRS (SI-NRS) ...........................................................................................46 
5.2.7. 
Worst Itch-Numerical Rating Scale (WI-NRS) ..........................................................47 
5.2.8. 
Psoriasis Symptom Diary (PSD) ................................................................................47 
5.2.9. 
Scalpdex ......................................................................................................................47 


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5.2.10. 
Dermatology Life Quality Index (DLQI) and Children’s Dermatology Life 
Quality Index (CDLQI) ..............................................................................................48 
5.3. 
Other Evaluations .......................................................................................................48 
5.3.1. 
Pharmacokinetics Assessment ....................................................................................48 
5.3.2. 
Dermal Imaging ..........................................................................................................48 
5.4. 
Final Study Visit .........................................................................................................48 
5.5. 
Early Termination Visit ..............................................................................................48 
5.6. 
Unscheduled Visit .......................................................................................................49 
5.7. 
Adverse Events ...........................................................................................................49 
5.7.1. 
Adverse Event Definition ...........................................................................................49 
5.7.2. 
Serious Adverse Event ................................................................................................49 
5.7.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) .....................................51 
5.7.4. 
Safety Review with Subject ........................................................................................51 
5.7.5. 
Adverse Event Reporting ............................................................................................51 
5.8. 
Reporting Pregnancy ..................................................................................................53 
5.9. 
Treatment Stopping Rules ..........................................................................................53 
6. 
DATA ANALYSIS ....................................................................................................54 
6.1. 
Statistical Methods ......................................................................................................54 
6.1.1. 
Determination of Sample Size ....................................................................................55 
6.1.2. 
Interim Analysis ..........................................................................................................55 
6.1.3. 
Background and Demographic Characteristics ..........................................................55 
6.1.4. 
Study Disposition........................................................................................................55 
6.1.5. 
Protocol Deviations and Eligibility Deviations ..........................................................55 
6.1.6. 
Investigational Product Application Compliance .......................................................55 
6.1.7. 
Pharmacokinetics Analysis .........................................................................................56 
6.2. 
Safety Analysis ...........................................................................................................56 
6.2.1. 
Adverse Events ...........................................................................................................56 
6.2.2. 
Clinical Laboratory Results ........................................................................................56 
6.2.3. 
Vital Signs ..................................................................................................................56 
6.2.4. 
Local Tolerance Assessments .....................................................................................56 
6.2.5. 
Medical History and Physical Examinations ..............................................................56 
6.3. 
Efficacy Evaluation ....................................................................................................56 


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6.3.1. 
Co-Primary Endpoints ................................................................................................57 
6.3.2. 
Secondary Endpoint ....................................................................................................57 
7. 
STUDY ADMINISTRATION ...................................................................................59 
7.1. 
Ethics ..........................................................................................................................59 
7.1.1. 
Ethics Review Board ..................................................................................................59 
7.1.2. 
Ethical Conduct of the Study ......................................................................................60 
7.1.3. 
Subject Information and Consent/Assent ...................................................................60 
7.2. 
Study Completion and Termination ............................................................................60 
7.2.1. 
Study Completion .......................................................................................................60 
7.2.2. 
Study Termination ......................................................................................................60 
7.3. 
Study Monitoring ........................................................................................................61 
7.4. 
Data Quality Assurance ..............................................................................................61 
7.5. 
Data Handling and Record Keeping ...........................................................................61 
7.6. 
Protocol Amendments and Deviations .......................................................................62 
7.7. 
Confidentiality and Privacy ........................................................................................62 
7.8. 
Conflict of Interest ......................................................................................................63 
7.9. 
Report Format .............................................................................................................63 
7.10. 
Publication Policy .......................................................................................................63 
8. 
REFERENCES ...........................................................................................................64 
9. 
APPENDICES ............................................................................................................65 
APPENDIX 1. BODY & SCALP DIAGRAM ...........................................................................65 
APPENDIX 2. PATIENT HEALTH QUESTIONNAIRE DEPRESSION SCALE 
(PHQ-8) ......................................................................................................................67 
APPENDIX 3. MODIFIED PATIENT HEALTH QUESTIONNAIRE DEPRESSION 
SCALE (PHQ-A) ........................................................................................................68 
APPENDIX 4. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C--SSRS) 
BASELINE/SCREENING VERSION .......................................................................69 
APPENDIX 5. COLUMBIA-SUICIDE SEVERITY RATING SCALE (C-SSRS) 
SINCE LAST VISIT VERSION ................................................................................72 
APPENDIX 6. PSORIASIS SYMPTOM DIARY ......................................................................75 
APPENDIX 7. SCALPDEX .......................................................................................................78 
APPENDIX 8. DERMATOLOGY LIFE QUALITY INDEX (DLQI) ......................................79 
APPENDIX 9. CHILDREN’S DERMATOLOGY LIFE QUALITY INDEX (CDLQI) ...........81 


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APPENDIX 10. COVID-19 STUDY SITE GUIDANCE ..........................................................83 
 
LIST OF TABLES 
Table 1: 
Excluded Medications and Treatments .......................................................................31 
Table 2: 
Laboratory Tests .........................................................................................................38 
 
 
LIST OF FIGURES 
Figure 1: 
Contraception Requirements for Female Subjects .....................................................37 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
Adverse Event 
AMP 
Adenosine Monophosphate 
B-IGA  
Body-Investigator Global Assessment of Disease 
BSA 
Body Surface Area 
Cmax 
Maximum Concentration 
CDLQI 
Children's Dermatology Life Quality Index 
CFB 
Change from Baseline 
COPD 
Chronic Obstructive Pulmonary Disease 
eCRF 
Case Report Form 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLQI 
Dermatology Life Quality Index 
EDC 
Electronic Data Capture  
ERB 
Ethics Review Board 
FDA 
U.S. Food and Drug Administration 
FOCBP 
Female of Childbearing Potential 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practices 
HC 
Health Canada 
IB 
Investigational Brochure 
IC50 
Half Maximal Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation 
ID 
Identification  
IGA 
Investigator Global Assessment 
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
kg 
Kilogram 
LED 
Light Emitting Device 


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Abbreviation 
Definition 
µg 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
Min 
Minute 
mITT 
Modified Intent to Treat 
mL 
Milliliter 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
NOAEL 
No Observed Adverse Effect Level 
NRS 
Numeric Rating Score 
P-450 
Cytochrome P450 
PASI 
Psoriasis Area and Severity Index 
PASI-75 
Psoriasis Area and Severity Index-75; subjects who achieve a 75% 
reduction in PASI from Baseline 
PDE-4 
Phosphodiesterase 4 
PHQ-8 
Patient Health Questionnaire  
PHQ-A 
Modified Patient Health Questionnaire for Adolescents 
PI 
Principal Investigator  
PK 
Pharmacokinetics 
PSD 
Psoriasis Symptoms Diary 
PSSI 
Psoriasis Scalp Severity Index 
PSSI-75 
Psoriasis Scalp Severity Index-75; subjects who achieve a 75% 
reduction in PSSI from Baseline 
QD 
Once Daily ("quaque die") 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation  
S-IGA 
Scalp-Investigator Global Assessment of Disease  
SI-NRS 
Scalp Itch-Numeric Rating Scale 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
ULN 
Upper Limit of Normal 
WI-NRS 
Worst Itch-Numeric Rating Scale 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Name of Sponsor/Company: Arcutis Biotherapeutics, Inc. 
Protocol Number:  
ARQ-154-309 
Phase: 3 
IND: 142047 
Protocol Title: A Phase 3, 8-Week, Parallel Group, Double Blind, Vehicle-Controlled Study 
of the Safety and Efficacy of ARQ-154 Foam 0.3% Administered QD in Subjects with Scalp 
and Body Psoriasis 
Clinical Indication: Scalp and Body Psoriasis  
Investigational Product: ARQ-154 foam investigational product (IP) will be supplied as 
ARQ-154 foam 0.3%. The active ingredient in ARQ-154 foam is roflumilast, a 
phosphodiesterase 4 (PDE-4) inhibitor. Matching vehicle foam will contain only excipients of 
ARQ-154 foam. 
Subjects will be randomized 2:1 to receive ARQ-154 foam 0.3% or matching vehicle foam 
once daily (QD) applied to all areas of scalp and body psoriasis. Areas of application will be 
all areas affected including face, scalp, trunk, or intertriginous/genital regions, with a 
maximum overall body surface area (BSA) of 25% (including a maximum non-scalp BSA of 
20%). Subjects should continue to apply IP to all treatment areas for the duration of the study 
regardless of whether treatable areas of psoriasis clear. New lesions that appear during the 
treatment period should also be treated. 
Study Design: This is a parallel group, double blind, vehicle-controlled study in which 
ARQ-154 foam 0.3% or vehicle foam is applied QD x 8 weeks to subjects with scalp and body 
psoriasis. Total BSA affected and treated will not exceed 25% (not including palms/soles). 
Primary Objective: The purpose of this study is to assess the safety and efficacy of ARQ-154 
foam 0.3% administered once daily (QD) vs. vehicle foam for 8 weeks in adolescent and adult 
subjects with scalp and body psoriasis.   
Study Sites: Approximately 45 sites in North America 
Number of Subjects (planned): Approximately 420 
Study Population: Subjects will be male and female adolescents (12-17 y/o) and adults 
(≥18 y/o). Subjects will have a minimum Scalp Investigator Global Assessment (S-IGA) = 
‘Moderate’ (3) and a minimum rest of the Body Investigator Global Assessment (B-IGA) = 
‘Mild’ (2) for study entry. Randomization will be stratified by study site, Baseline S-IGA 
(3 vs. 4), and Baseline B-IGA (2 vs. ≥3).   


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Duration of Participation for Subjects: Screening (up to 4 weeks) + Treatment phase 
(8 weeks) for a total of up to approximately 12 weeks. 
Main Criteria for Inclusion:  
1. For adult subjects: Participants legally competent to read, write, and sign and give 
informed consent. For adolescent subjects: Informed consent of a parent(s) or legal 
guardian, and assent by the subjects, as required by local laws. 
2. Males and females ages 12 years and older (inclusive) at the time of consent or assent. 
3. Scalp psoriasis with a Scalp-Investigator Global Assessment of Disease (S-IGA) 
severity of at least Moderate (‘3’) at Baseline. 
4. Extent of scalp psoriasis involving ≥ 10% of the total scalp at Baseline.  
5. A Psoriasis Scalp Severity Index (PSSI) of at least 6 at Baseline.  
6. An IGA of body (i.e., non-scalp) psoriasis (B-IGA) of at least Mild (‘2’) at Baseline. 
7. A PASI score of at least 2 (excluding palms and soles) at Baseline. 
8. Clinical diagnosis of psoriasis vulgaris of at least 6 months duration at Screening as 
determined by the Investigator. Stable disease for the past 4 weeks. 
9. Total overall psoriasis involvement on scalp and non-scalp areas ≤ 25% BSA 
(not including palms/soles) at Baseline.  Total non-scalp BSA should not exceed 20%. 
10. Female subject of childbearing potential (FOCBP) must have a negative serum 
pregnancy test at Screening (Visit 1) and negative urine pregnancy test at Baseline 
(Visit 2). In addition, sexually active FOCBP must agree to use at least one form of 
highly effective contraception or a barrier method of contraception throughout the 
study according to Contraception Requirements (Figure 1).  
11. Females of non-childbearing potential must either be premenarchal, post-menopausal 
with spontaneous amenorrhea for at least 12 months (post-menopausal status will be 
confirmed with FSH testing) or have undergone surgical sterilization according to 
Contraception Requirements. Prepubescent females must agree to be abstinent during 
the study (Figure 1).  
12. Subjects in good health as judged by the Investigator, based on medical history, 
physical examination, vital signs, serum chemistry labs, hematology values, and 
urinalysis. 
13. Subjects are considered reliable and capable of adhering to the Protocol and visit 
schedule according to the Investigator judgment.  




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11. Subjects with PHQ-8 (≥18 years old, inclusive) or modified PHQ-A (adolescents, 
12 to 17 years old, inclusive) score ≥10 at Screening or Baseline visits. 
12. History of severe depression, suicidal ideation or behavior, Baseline/Screening 
C-SSRS (for adolescents and adults 12 years old and older) indicative of suicidal 
ideation or behavior, whether lifetime or recent/current. 
13. Females who are pregnant, wishing to become pregnant during the study, or are 
breast-feeding. 
14. Previous treatment with ARQ-151 or ARQ-154. 
15. Subjects who have received oral roflumilast (Daliresp®, Daxas®), or apremilast 
(Otezla®) within the past 4 weeks prior to Baseline.  
16. Subjects with any serious medical condition or laboratory abnormality that would 
prevent study participation or place the subject at significant risk, as determined by the 
Investigator. 
17. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation 
of the investigational product. 
18. Subjects who had a major surgery within 4 weeks prior to Baseline or have a major 
surgery planned during the study. 
19. Subjects who are unable to communicate, read or understand the local language, or 
who display another condition, which in the Investigator’s opinion, makes them 
unsuitable for clinical study participation.  Parent(s)/legal guardian(s) of adolescent 
subjects who are unable to communicate, read, or understand the local language. 
20. Subjects with a current or a history of cancer within 5 years, with the exception of fully 
treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma or 
carcinoma in situ of the cervix. 
21. Subjects with active infection that required oral or intravenous administration of 
antibiotics, antifungals, or antiviral agents within 7 days of Baseline. 
22. Subjects who are family members of the clinical study site, clinical study staff, or 
sponsor, or family members residing in the same household of enrolled subjects. 
23. Subjects unable to apply product to the scalp (and/or psoriasis elsewhere) due to 
physical limitations. 
24. Any condition that in the Investigator’s assessment would preclude the subject from 
participating in the study. 


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Key Assessments: Safety will be monitored through application site assessments, vital 
signs/weight, physical examinations, safety labs, and Adverse Events (AEs). Safety will also 
be monitored by C-SSRS, and PHQ-8 (in adults) or modified PHQ-A (adolescents 12-17 y/o) 
assessments. 
All AEs that occur after the first application of IP through the end of the study should be 
collected. All SAEs should be collecting starting at Screening. 
Efficacy assessments will be evaluated utilizing: 
• Scalp-IGA (S-IGA) 
• Body-IGA (B-IGA) 
• Psoriasis Scalp Severity Index (PSSI) 
• Extent of Scalp Involvement  
• Body Surface Area (BSA) 
• Psoriasis Area and Severity Index (PASI) 
• Worst Itch-Numeric Rating Scale (WI-NRS) 
• Scalp Itch-Numeric Rating Scale (SI-NRS) 
• Scalpdex 
• Dermatology Life Quality Index (DLQI) in subjects ≥ 17 years old 
• Children's Dermatology Life Quality Index (CDLQI) in subjects 12-16 years old 
• PSD (Psoriasis Symptom Diary) in subjects ≥ 18 years old  
Study Endpoints:  
The co-Primary Efficacy Endpoints will be: 
• S-IGA Success, defined as achievement of Scalp-IGA (S-IGA) score of ‘Clear’ or 
‘Almost Clear’ plus a 2-grade improvement from Baseline 
• B-IGA Success, defined as achievement of Body-IGA (B-IGA) score of ‘Clear’ or 
‘Almost Clear’ plus a 2-grade improvement from Baseline 
The Secondary Efficacy Endpoints will include: 
• For subjects with Baseline Scalp Itch (SI) NRS score ≥4, achievement of ≥4-point 
improvement from Baseline in SI-NRS at Week 8 (“SI-NRS Success at Week 8”) 
• SI-NRS Success at Week 4 
• SI-NRS Success at Week 2 
• SI-NRS Change from Baseline (CFB) at Week 1 
• SI-NRS CFB at 72 hours 




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• SI-NRS Success at Week 8 
• SI-NRS Success at Week 4 
• SI-NRS Success at Week 2 
• SI-NRS CFB at Week 1 
• SI-NRS CFB at 72 hours 
Family 2 (α=0.005): 
• WI-NRS Success at Week 8 
• PASI-75 at Week 8 
• CFB in PSD Items related to Itching, Pain, and Scaling (Questions 1, 9, and 11) 
aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• PSSI-75 at Week 8 
Family 3 (α=0.01): 
• S-IGA score of ‘clear’ at Week 8 
• S-IGA Success at Week 4 
• CFB in PASI at Week 2 
• S-IGA Success at Week 2 
• PSD Total Score = 0 at Week 8 
• SI-NRS CFB at Day 1 
The Fallback Method will be used to pass unused alpha.  The Families will be tested in this 
order:  Family 2, Family 1, Family 3.   Testing will be sequential within Family 2 and Family 
1, with the order of testing within each family as listed above.  Testing within Family 3 will be 
implemented with a Holm’s procedure.   
To start, Family 2 will be tested, sequentially within Family 2, at the α=0.005 level.  Should 
the testing succeed through all seven endpoints in Family 2, the α=0.005 will remain unused, 
and will be passed to Family 1.  
The testing of the five SI-NRS endpoints in Family 1 will be sequential, either at the α=0.01 
level (assumes Family 2 had an unsuccessful test), or the α=0.015 level (assumes all endpoints 
in Family 2 were successful at the α=0.005 level). 




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1.2. 
Study Schema 
 
 
 
 
 
 
 
 
 
Screening (Visit 1) 
Baseline (Visit 2) 
Randomization and Treatment Day 1 
ARQ-154 
Foam 0.3% 
Vehicle 
Foam  
8-Week Treatment Period 
(Visits 3, 4, & 5) 
A Phase 3, 8-Week, Parallel Group, Double Blind, 
Vehicle-Controlled Study of the Safety and Efficacy of ARQ-154 
Foam 0.3% Administered in Subjects with Scalp and Body 
Psoriasis 
 
 
Approximately 420 adolescent and adult subjects with scalp and 
body psoriasis will be randomized 2:1 to receive either: 
• ARQ-154 foam 0.3%, or 
• Vehicle foam 


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1.3. 
Schedule of Visits and Assessments 
Study Procedure 
Screening 
Baseline 
Day 1 
Week 2 
Day 15 
Week 4 
Day 29 
Week 8a 
Day 57 
Visit 
1 
2 
3 
4 
5 
Visit Window 
-4 Weeks 
 
± 3 Days 
± 5 Days 
± 5 Days 
Informed consent/assent 
X 
 
 
 
 
Medical/surgical history, demography 
X 
 
 
 
 
Physical examinationb 
X 
X 
 
 
X 
Fitzpatrick Skin Type 
X 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
Randomization 
 
X 
 
 
 
Hematology, Chemistry, and Urinalysisc 
X 
X 
 
X 
X 
Vital signs, weight, heightd 
X 
X 
X 
X 
X 
S-IGAe, B-IGAe, PSSIe, BSAf, Extent of 
Scalp Involvementg, PASI 
X 
X 
X 
X 
X 
DLQI/CDLQIh, Scalpdexh, PSDh 
X 
X 
X 
X 
X 
Daily SI-NRS and WI-NRSi at home 
(non-clinic) 
Day -7 through Day 57 
Application Site Reaction Assessment/ 
Local Tolerabilityj  
 
X 
X 
X 
X 
C-SSRS, PHQ-8/PHQ-Ak 
X 
X 
 
X 
X 
Medical Photographyl 
 
X 
X 
X 
X 
Follicle Stimulating Hormone (FSH) m 
X 
 
 
 
 
Serum pregnancy testm 
X 
 
 
 
 
Urine pregnancy testn 
 
X 
 
X 
X 
 
 
 
 
 
 
IP application and subject/family trainingp 
 
X 
X 
X 
 
Dispense investigational product kitq 
 
X 
X 
X 
 
Dispense / review dosing diary 
 
X 
X 
X 
X 
Weigh investigational productr 
 
X 
X 
X 
X 
Compliance calculations 
 
 
X 
X 
X 
Adverse event assessmentt 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
 




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Footnotes from table above: 
t. 
All AEs should be collected starting after the first application of the IP through the end of the study. All SAEs 
should be collected starting after the signing of the informed consent through 30 days after the last day of the IP 
application or the end of the study (whichever is later). Any AEs (whether serious or non-serious) and clinically 
significant abnormal laboratory test value(s) will be evaluated by the Investigator and treated and/or followed 
up to 30 days after end of treatment or until symptoms or value(s) return to subject’s Baseline, or acceptable 
level, as judged by the PI. 
2. 
BACKGROUND AND RATIONALE 
2.1. 
Introduction 
Roflumilast is a phosphodiesterase 4 (PDE-4) inhibitor approved globally to reduce the risk of 
exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) associated 
with chronic bronchitis.  Roflumilast and its active metabolite, roflumilast N-oxide, are high 
affinity selective inhibitors of PDE-4 (a major cyclic-3′,5′-adenosine monophosphate 
(cyclic AMP)-metabolizing enzyme), whose activity leads to accumulation of intracellular cyclic 
AMP.  There are four different subtypes of PDE-4: PDE-4a, PDE-4b, PDE-4c, and PDE-4d, each 
with several isoforms (splicing variants).  IC50 values of both roflumilast and roflumilast N-oxide 
for the different PDE-4 isoforms and subtypes are mostly sub-nanomolar and single digit 
nanomolar (Hatzelmann 2010).  The PDE-4 family of enzymes are the most prevalent 
phosphodiesterases in immune cells and inhibition of PDE-4 subtypes has been associated with 
anti-inflammatory effects in many biological systems. 
Psoriasis is a chronic inflammatory skin disease characterized by raised, well-demarcated, 
erythematous oval plaques with adherent silvery scales.  Numerous past reports have suggested a 
deficiency of cyclic AMP-dependent protein kinases in human psoriatic skin (Brion 1986).  More 
recently, various cytokines produced by Th1 and Th17 cells have been shown to play a crucial 
role in the pathogenesis of psoriasis.  It has been postulated that the anti-inflammatory effects of 
PDE-4 inhibitors may provide a beneficial therapeutic intervention in the treatment of chronic 
plaque psoriasis, and Otezla® (apremilast) a PDE-4 inhibitor has been approved for the oral 
treatment of chronic plaque psoriasis. 
The scalp is a common area of psoriasis involvement, and often the first area on the body to be 
affected.  The scalp is considered an underdiagnosed, undertreated, and difficult to manage area 
for psoriasis.  Scalp psoriasis may be associated with pruritus, pain, flaking, and hair loss, and 
may disproportionately impact quality of life relative to psoriasis elsewhere.  Treatment of scalp 
psoriasis is often limited to topical therapy, unless there are sufficient additional non-scalp 
psoriasis to merit systemic treatment.  Intralesional therapy represents another approach.  Current 
treatment options for scalp psoriasis include topical steroids, vitamin D derivatives, tar 
preparations, and salicylic acid products, but considerable unmet need remains for safe and 
effective products (Blakely 2016, Schlager 2016, Wang 2017, Merola 2018, Kivelevitch 2018).  
Given the scalp is a hair-bearing site, choice of formulation is critical, and foams are a favored 
option. 










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• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• PSSI-75 at Week 8  
• S-IGA score of ‘Clear’ at Week 8 
• S-IGA Success at Week 4 
• CFB in PASI at Week 2 
• S-IGA Success at Week 2 
• PSD Total Score = 0 at Week 8 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This is a phase 3, parallel group, double blind, vehicle-controlled study in which ARQ-154 foam 
0.3% or vehicle foam is applied QD x 8 weeks to adolescent and adult subjects with a minimum 
Scalp Investigator Global Assessment (S-IGA) of ‘Moderate’ (3) and a minimum rest of the 
Body Investigator Global Assessment (B-IGA) of ‘Mild’ (2).  
4.2. 
Number of Sites and Subjects 
A total of up to approximately 420 subjects will be enrolled at approximately 45 study sites in 
North America. Additional countries or study sites may be added, as necessary. Subjects will be 
male and female adolescents (12 – 17 y/o) and adults (≥18 y/o). Subjects must have no more than 
25% BSA total across scalp and body psoriasis not including palm/soles (non-scalp BSA must 
not exceed 20%). All lesions on a subject will be treated including the scalp, face, trunk, and 
intertriginous areas. 
4.3. 
Subject Participation 
Subject participation involves a minimum of 5 clinic visits, including Screening, Baseline/Day 1, 
Week 2, Week 4, and Week 8. The interval between Screening and Baseline visits may take up 
to 4 weeks, the anticipated maximum duration of subject participation is approximately 
12 weeks. 
4.4. 
Subject Identification Number Assignment 
All subjects who sign an informed consent or assent (adolescents) form will be assigned a unique 
5-digit subject identification (ID) number by the interactive web response system (IWRS). The 
first 2 digits correspond to the site number (assigned by the Sponsor), the next 3 digits 
(starting with 900) correspond to the sequential order in which the subject is screened for the 


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study (e.g., Subject ID <11900>: Site 11, subject number 900, as the first subject screened by 
that site). The subject ID will remain the same in the event the subject is rescreened. 
The study site is responsible for maintaining a current log of subject ID number assigned to each 
subject. The subject ID number will be used to identify the subject throughout the study and 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.). 
4.5. 
Selection of Study Population 
4.5.1. 
Inclusion Criteria 
Subjects must fulfill all the following inclusion criteria to be eligible for participation in the 
study: 
1. For adult subjects: Participants legally competent to read, write, and sign and give 
informed consent. For adolescent subjects: Informed consent of a parent(s) or legal 
guardian, and assent by the subjects, as required by local laws. 
2. Males and females ages 12 years and older (inclusive) at the time of consent or assent. 
3. Scalp psoriasis with a Scalp-Investigator Global Assessment of Disease severity (S-IGA) 
of at least Moderate (‘3’) at Baseline. 
4. Extent of scalp psoriasis involving ≥ 10% of the total scalp at Baseline.  
5. A Psoriasis Scalp Severity Index (PSSI) of at least 6 at Baseline.  
6. An IGA of body (i.e., non-scalp) psoriasis (B-IGA) of at least Mild (‘2’) at Baseline. 
7. A PASI score of at least 2 (excluding palms and soles) at Baseline. 
8. Clinical diagnosis of psoriasis vulgaris of at least 6 months duration at Screening as 
determined by the Investigator. Stable disease for the past 4 weeks. 
9. Total overall psoriasis involvement on scalp and non-scalp areas ≤ 25% BSA 
(not including palms/soles) at Baseline. Total non-scalp BSA should not exceed 20%. 
10. Female subject of childbearing potential (FOCBP) must have a negative serum pregnancy 
test at Screening (Visit 1) and negative urine pregnancy test at Baseline (Visit 2). In 
addition, sexually active FOCBP must agree to use at least one form of highly effective 
contraception or a barrier method of contraception throughout the study according to 
Contraception Requirements (Figure 1).  
11. Females of non-childbearing potential must either be premenarchal, post-menopausal 
with spontaneous amenorrhea for at least 12 months (post-menopausal status will be 
confirmed with FSH testing) or have undergone surgical sterilization according to 
Contraception Requirements. Prepubescent females must agree to be abstinent during the 
entire course of the study (Figure 1).  
12. Subjects in good health as judged by the Investigator, based on medical history, physical 
examination, vital signs, serum chemistry labs, hematology values, and urinalysis. 


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13. Subjects are considered reliable and capable of adhering to the Protocol and visit 
schedule according to the Investigator judgment. 
4.5.2. 
Exclusion Criteria 
Subjects who meet any of the following exclusion criteria will be excluded from participation in 
the study: 
1. Subjects who cannot discontinue treatment with therapies for the treatment of psoriasis 
vulgaris prior to the Baseline visit and during the study according to Excluded 
Medications and Treatments (Table 1). 
2. Planned excessive exposure to treated area(s) to either natural or artificial sunlight, 
tanning bed, or other LED. 
3. Subjects currently taking lithium or antimalarial drugs. 
4. Planned initiation or changes to concomitant medication that could, in the opinion of the 
Investigator, affect psoriasis vulgaris (e.g., beta blockers or ACE inhibitors if not on 
stable dose for at least 8 weeks). 
5. Current diagnosis of non-plaque forms of psoriasis (e.g., guttate, erythrodermic/ 
exfoliative, palmoplantar only involvement, or pustular psoriasis). Current diagnosis of 
drug-induced psoriasis. 
6. Subjects with any condition on the treatment area which, in the opinion of the 
Investigator, could confound efficacy measurements. 
7. Known allergies or hypersensitivity to component(s) of the investigational product 
 
 
 
 
8. Subjects who cannot discontinue the use of strong systemic P-450 cytochrome inhibitors 
(e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, 
nefazodone, saquinavir, suboxone and telithromycin) for two weeks prior to the Baseline 
visit and during the study period.  
9. Known or suspected:  
a. Known HIV infection 
b. Severe renal insufficiency as evidenced by calculated creatinine clearance 
<30 mL/min or estimated glomerular filtration rate <30mL/min/1.73cm2  
c. Moderate to severe hepatic disorders (Child-Pugh B or C) 
10. Liver functions tests results that exceed: 
 AST or ALT > 2x ULN 
 Total bilirubin: 
  1.5 x ULN or 
 > ULN and ≤ 1.5 x ULN AND direct bilirubin is > 35% of total bilirubin 
 ALP ≥ 2x ULN 


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11. Subjects with PHQ-8 (≥18 years old, inclusive) or modified PHQ-A (adolescents, 
12 to 17 years old, inclusive) score ≥10 at Screening or Baseline visits. 
12. History of severe depression, suicidal ideation or behavior, Baseline/Screening C-SSRS 
(for adolescents and adults 12 years old and older) indicative of suicidal ideation or 
behavior, whether lifetime or recent/current. 
13. Females who are pregnant, wishing to become pregnant during the study, or are 
breast-feeding. 
14. Previous treatment with ARQ-151 or ARQ-154. 
15. Subjects who have received oral roflumilast (Daliresp®, Daxas®), or apremilast 
(Otezla®) within the past 4 weeks prior to Baseline.  
16. Subjects with any serious medical condition or laboratory abnormality that would prevent 
study participation or place the subject at significant risk, as determined by the 
Investigator. 
17. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of 
the investigational product. 
18. Subject had a major surgery within 4 weeks prior to Baseline or have a major surgery 
planned during the study. 
19. Subjects with who are unable to communicate, read or understand the local language, or 
who display another condition, which in the Investigator’s opinion, makes them 
unsuitable for clinical study participation.  Parent(s)/legal guardian(s) of adolescent 
subjects who are unable to communicate, read, or understand the local language. 
20. Subjects with a current or a history of cancer within 5 years, with the exception of fully 
treated Cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma 
in situ of the cervix. 
21. Subjects with active infection that required oral or intravenous administration of 
antibiotics, antifungals, or antiviral agents within 7 days of Baseline. 
22. Subjects who are family members of the clinical study site, clinical study staff, or 
sponsor, or family members residing in the same household of enrolled subjects. 
23. Subjects unable to apply product to the scalp (and/or psoriasis elsewhere) due to physical 
limitations. 
24. Any condition that in the Investigator’s assessment would preclude the subject from 
participating in the study. 
4.6. 
Randomization 
Randomization will take place at the Baseline (Day 1) visit after the Investigator confirms the 
subject to be fully eligible for participation as outlined in Section 4.5. Subjects will be randomly 
assigned to apply ARQ-154 foam 0.3% QD or vehicle foam QD. Assignment of ARQ-154 or 
vehicle will be made at a 2:1 ratio and will be stratified by study site, Baseline S-IGA (3 vs. 4), 


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and Baseline B-IGA (2 vs. ≥ 3) according to a computer-generated randomization list. Kits 
containing canisters of IP will be assigned to each subject using the IWRS. A subject may 
receive more than one kit for the treatment period. The kits and canisters are blinded and each kit 
is numbered with a unique kit number.  
4.7. 
Prohibitions and Concomitant Therapy 
Prohibited medications and products are detailed in Table 1. 
Generally, the addition of new medications, including nonprescription medications, during 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 
transcribed to Case Report Forms.  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 ‘Excluded Medications and Treatments’ (Table 1). 
Table 1: 
Excluded Medications and Treatments 
Excluded Medications and Treatments 
Wash Out Period Prior to 
Baseline (Day 1) 
Etanercept 
4 weeks 
Adalimumab, infliximab 
8 weeks 
All other Biologics 
12 weeks or 5 half-lives, 
whichever is longer 
Systemic corticosteroids, retinoids, apremilast, roflumilast, 
methotrexate, cyclosporine, fumarates, and other systemic 
immunosuppressants 
4 weeks 
Shampoos containing coal tar, keratolytics including salicylic acid, 
antifungals, zinc pyrithione, selenium sulfide, or medical devices 
1 week 
Topical medications used on the scalp for conditions besides 
psoriasis, e.g., use of topical minoxidil for androgenetic alopecia 
2 weeks 
Topical anti-psoriasis medications (e.g., topical corticosteroids 
including corticosteroid shampoos, vitamin D analogs) 
2 weeks 
Strong systemic P-450 cytochrome inhibitors (e.g. indinavir, 
nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, 
nefazodone, saquinavir, suboxone and telithromycin) 
2 weeks 
PUVA or UVB phototherapy 
4 weeks  


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Table 1: 
Excluded Medications and Treatments (Continued) 
Note:   
1. 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 Screening and are continued at the 
same dose throughout the study. 
2. Non-medicated emollients, moisturizers and sunscreens will be allowed as used normally by the subjects. 
These can be applied to non-treated areas as needed and should not be used within 12 hours of a study visit. 
3. No emollients or moisturizers should be applied on treated areas. 
Only non-medicated shampoos are permitted. Medicated shampoos (e.g., coal tar, keratolytics including salicylic 
acid, antifungals, zinc pyrithione, selenium sulfide, corticosteroids, medical devices) are prohibited.  Subjects should 
not use other hair products for at least an hour before or after application of investigational product.   
4.8. 
Treatment 
4.8.1. 
IP Supplies, Packaging, and Labeling 
ARQ-154 foam 0.3% or vehicle foam will be provided in a canister containing approximately 
60 grams of foam. Two canisters of IP will be packed in kits. The number of kits dispensed to a 
subject will be based on the BSA involvement. The kits and canisters will be labeled with a 
unique number to maintain blinding. 
The Sponsor will supply sufficient quantities of the IP (ARQ-154 foam 0.3%, and matching 
vehicle) to each site to allow for completion of this study. The matching vehicle foam will 
contain only excipients of ARQ-154 foam. 
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 Manual for details on the accountability, 
storage, and management of ARQ-154 and matching vehicle. 
Excluded Medications and Treatments 
Wash Out Period Prior to 
Baseline (Day 1) 
Investigational drugs 
12 weeks (biologics) or  
5 half-lives, whichever is longer; 
5 half-lives (orals);  
2 weeks (topical) 
Sedating antihistamines including over the counter products 
containing sedating antihistamines 
Note: Systemic treatments with nonsedating antihistamines 
(e.g., cetirizine, desloratadine, loratadine) in a stable regimen is 
allowed. 
1 week 


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4.8.2. 
Treatment Administration 
Initial treatment with the IP will occur on Baseline/Day 1. At the randomization visit (Baseline), 
the study staff will demonstrate to the subject/parent(s)/caregiver(s) how to apply ARQ-154 
foam 0.3% or vehicle foam using the first canister from the kit that is assigned to the subject at 
randomization. Study site staff will be trained to ensure a proper amount is dispensed from the 
foam can and applied to psoriasis lesion(s) as a thin film and rubbed in thoroughly but gently, 
until the ‘white’ has disappeared. For scalp lesions, special attention should be given to 
ensuring adequate investigational product is applied to scalp skin and not rubbed off on 
hair. The subject/parent(s)/caregiver(s) will then practice dispensing a similar amount of 
investigational product and applying to scalp and body psoriasis lesion(s). The study staff will 
confirm that the subject’s application technique is correct. 
Subjects/parent(s)/caregiver(s) will be instructed to apply IP QD in the evening (except at 
Baseline and Week 2, in which case IP will be applied at the study site) to areas of scalp and 
body psoriasis lesions identified by the Investigator at Baseline using a Body and Scalp Diagram 
(see Appendix 1). IP will be applied at least 20 minutes before going to bed. 
For Scalp Lesions: IP will be applied when the skin and hair on the scalp is dry. Subjects should 
dispense IP on their fingers, then part hair where there are lesions and rub IP into scalp skin. As 
the IP is applied, the subject should move any hair away to ensure that sufficient foam is applied 
directly to the affected skin on the scalp. Subjects should not use other hair products for at least 
an hour before or after application. 
For Non-scalp Lesions: IP should be applied to affected areas as a thin layer and rubbed in 
thoroughly but gently until the foam has disappeared. 
Subjects should not wash areas (or otherwise expose to water, e.g., swimming) where ARQ-154 
foam or vehicle has been applied until at least 4 hours after IP application and preferably not 
until the following morning. 
Subjects should continue to apply IP to all treatment areas for the duration of the study regardless 
of whether treatable areas of psoriasis clear. New lesions that appear during the treatment period 
should also be treated. Application will be to all areas affected including the face, scalp, and 
intertriginous areas. A Body and Scalp Diagram (see Appendix 1) should be used to record 
existing and new areas of scalp and body psoriasis involvement that are subject to treatment.  
4.8.3. 
Treatment Compliance 
Weight of the IP applied will be measured for reporting purposes. Each IP canister will be 
weighed individually prior to dispensing at the Baseline visit or subsequent visits. IP canisters 
must be returned by subjects at each study visit (both empty and full) and will be weighed 
individually. Record IP canister weight in the source notes and in the eCRF. 
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 or 
reason for missed dose.  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 eCRFs. If a subject misses a scheduled dose, they should be 


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instructed to return to the protocol IP administration schedule (i.e., if subject forgets a dose they 
should wait until that evening 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 entire IP application period (Baseline to Week 8) 
and does not miss more than 3 consecutive doses. 
Compliance will be assessed by review of the dosing diary. Re-training will be conducted at 
subsequent visits as needed, i.e., if the returned canister weighs substantially different than the 
expected weight, the diary shows less than 80% of expected use, or more than 3 consecutive 
doses are missed. 
Compliance will be documented in the source and eCRF. 
4.8.4. 
Blinding 
This is a double-blinded study, therefore neither the subjects nor the Investigator, clinical 
personnel, or Sponsor will be aware of which treatment an individual subject receives. 
4.8.5. 
Breaking Treatment Codes 
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 IWRS system 
for that subject. Refer to the current version of the ARQ-154-309 IWRS 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 eCRF, along with the 
date on which the treatment assignment was obtained. The Investigator is requested to contact 
the Medical Monitor promptly in the event of any treatment unblinding. 
Blinding of study treatment is critical to the integrity of this clinical study 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. 
4.8.6. 
Removal of Subjects from Investigational Product 
A subject may discontinue from receiving the IP for any of the following reasons: 
• Occurrence of any medical condition or circumstance that, in the opinion of the 
Investigator, exposes the subject to substantial risk and/or does not allow the subject 
to adhere to the requirements for IP administration as per the Protocol. 
• Occurrence of or considerable worsening of an AE (described in Section 5.7) that, in 
the opinion of the Investigator in consultation with the Medical Monitor and Sponsor, 
represents an unacceptable risk to the subject if he/she continues in the study.  
The Investigator must follow the subject until the AE resolves or satisfactorily 
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• IP application must be discontinued immediately in the event of a female subject’s 
pregnancy. 
• Subject’s decision to withdraw from receiving IP. 
• Weight loss of >5% from Baseline, if not dieting or intentionally trying to lose 
weight, at the Investigator’s discretion and after consultation with the Medical 
Monitor and Sponsor. 
• C-SSRS indicative of suicidal ideation 
• PHQ-8/PHQ-A score ≥15 if determined by Investigator in consultation with a mental 
health professional. 
• Requirement for use of prohibited concomitant medication (Table 1) after 
consultation with the Sponsor and Medical Monitor. 
• Subjects repeated failure to comply with protocol requirements or study related 
procedures. 
4.8.7. 
Removal of Subjects from the Study 
A subject may be removed from study participation for any of the following reasons: 
• Subject’s decision to withdraw from the study. 
• Subject’s death. 
• 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. 
5. 
STUDY PROCEDURES 
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 Investigator and/or the Sponsor for reasons 
related to subject safety. 
5.1. 
Safety Assessments 
This study assesses the safety and efficacy of ARQ-154 foam 0.3%. Safety will be determined by 
evaluating physical examinations, vital signs/weight, local tolerability assessments, clinical 
laboratory parameters, PHQ-8/PHQ-A, C-SSRS, 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. 


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5.1.1. 
Screening 
Before a subject’s participation in the clinical study, the Investigator is responsible for obtaining 
written informed consent from the subject or written assent from adolescent subjects and consent 
from their parent(s) or legal guardian(s) after adequate explanation of the study design, 
anticipated benefits, and the potential risks. Informed consent must be obtained before 
completion of any non-standard of care study-specific procedures. Procedures that are part of 
standard of care are not considered study-specific and, therefore, may be performed prior to 
obtaining consent and used to confirm eligibility provided they occur within the time allowance 
outlined in the Schedule of Visits and Assessments (Section 1.3). A subject is considered a 
participant of the study once the informed consent form (ICF) (and written assent for an 
adolescent subject) is completely signed. 
The following procedures/assessments will be performed at the Screening Visit (within 4 weeks 
after signing the ICF/assent): 
• Review of medical and surgical history 
• Review of childbearing potential (female subjects) and contraceptive use 
(Section 5.1.2)  
• Collection of demographic data including age, sex, race, ethnicity  
• Limited physical examination of skin (including assessment of Fitzpatrick Skin Type 
at Screening only), lungs, heart 
• Vitals signs including temperature, heart rate, blood pressure 
• Collection of height (cm) and body weight (kg)  
• Laboratory tests: hematology, chemistry, urinalysis, serum pregnancy (for female 
subjects of childbearing potential) and FSH (to confirm post-menopausal status) 
• Scalp and body psoriasis assessments: S-IGA, B-IGA, PSSI, BSA, PASI 
• Completion of DLQI/CDLQI, Scalpdex, PSD 
• C-SSRS, PHQ-8/PHQ-A 
• Collection of prior and concomitant medication 
All screened subjects will receive a subject identification number (see Section 4.4) and be 
entered into the eCRF. Subjects that fail to meet the eligibility criteria will be designated as a 
screen failure and entered in the IWRS and eCRF as such. Subjects who are unable to enroll 
within the screening window will be rescreened.  
Subjects may be re-screened one time. The original assigned subject ID number will be used for 
re-screening. 
Subjects who consent but do not proceed with enrollment will be considered a screen fail. 


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5.1.2. 
Contraception Requirements 
Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at 
Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2), Week 4 (Visit 4) 
and Week 8 (Visit 5). In addition, sexually active FOCBP must agree to use at least one form of 
a highly effective or barrier method of contraception throughout the study according to 
Contraception Requirements for Female Subjects. Prepubescent females must agree to be 
abstinent during the entire course of the study (Figure 1).  
Figure 1: 
Contraception Requirements for Female Subjects 
 
 
5.1.3. 
Baseline 
Each subject will undergo Baseline assessments outline in the Schedule of Visits and 
Assessments (Section 1.3). For subjects <18years, if the Baseline (Day 1) visit occurs within 
3 weeks of Screening, the Screening lab results may be utilized.  
Randomization and IP kit assignment will take place via IWRS after the subject has been found 
to be fully eligible for participation. A subject will be considered enrolled into the study upon the 
first IP application. 
5.1.4. 
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 (including assessment of Fitzpatrick skin 
type at Screening only), lungs, and heart only.  


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Fitzpatrick skin phototype assessment will be rated as follows: 
I. 
Always burns easily; never tans (sensitive) 
II. 
Always burns easily; tans minimally (sensitive) 
III. 
Burns moderately; tans gradually (light brown) (normal) 
IV. 
Burns minimally; always tans well (moderate brown) (normal) 
V. 
Rarely burns; tans profusely (dark brown) (insensitive) 
VI. 
Never burns; deeply pigmented (insensitive) 
5.1.5. 
Vital Signs, Height and Weight 
Vital signs will be performed according to the Schedule of Visits and Assessments (Section 1.3).  
Blood pressure, heart rate, and temperature will be measured while the subject is sitting/resting 
for at least 5 minutes. 
Height will be collected at Screening and Week 8. 
Subjects should void prior to weight being taken and remove any objects of significant weight 
(i.e., jackets, outerwear, shoes, cell phones, wallet, key chains, etc.). A 5% unintentional weight 
loss from Baseline should be reported to the medical monitor. 
5.1.6. 
Laboratory Tests 
All tests listed in Table 2 will be performed according to the Schedule of Visits and Assessments 
(Section 1.3) unless otherwise noted. For subjects <18 years old, Screening safety lab results 
collected within 3 weeks of the Baseline visit may be utilized as the Baseline safety lab 
assessment. No food restrictions are required for the collection of specimens. In addition, 
laboratory safety tests may be performed at unscheduled time points, if deemed necessary by the 
Investigator. Laboratory samples will be sent to the central lab. Refer to the most current Central 
Laboratory Manual for collection, processing, shipping, and report receipt instructions. 
Table 2: 
Laboratory Tests 
Hematology 
Serum Chemistry 
• Hemoglobin 
• Hematocrit  
• Total and differential leukocyte count 
• Red blood cell count with indices and 
morphology 
• Platelet count 
• Blood Urea Nitrogen 
• Bilirubin (total and direct) 
• Alkaline phosphatase 
• Aspartate aminotransferase 
• Alanine aminotransferase 
• Albumin 
• Sodium 
• Potassium 
• Chloride 
• Glucose 
• Creatinine  


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Table 2: Laboratory Tests (Continued) 
Urinalysis 
Additional Tests 
• pH 
• Specific gravity 
• Protein* 
• Glucose 
• Ketones 
• Bilirubin 
• Blood* 
• Nitrite* 
• Urobilinogen 
• Leukocyte esterase* 
• Urine pregnancy test** 
• (for females of childbearing potential only) 
• Serum pregnancy test (hCG)*** 
• FSH**** 
• Pharmacokinetic (PK) assessments 
* 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. 
** Baseline, Weeks 4, and 8, for FOCBP only  
*** At Screening, for FOCBP only 
****At Screening, for postmenopausal females only  
5.1.7. 
Patient Health Questionnaire Depression Scale (PHQ-8) 
The PHQ-8 Assessment (see Appendix 2) will be completed by adult subjects according to the 
Schedule of Visits and Assessments (Section 1.3). 
PHQ-8 score is the sum of the responses for the 8 questions. 
Five severity categories of depression are defined as follows: 
• None – Minimal depression (1 to 4) 
• Mild depression (5 to 9) 
• Moderate depression (10 to 14) 
• Moderately severe depression (15 to 19) 
• Severe depression (20 to 24) 
Subjects with a PHQ-8 score of 10-14 should be referred to a mental health professional for 
evaluation, regardless of the reason for their change in score. 
Subjects with a PHQ-8 score of ≥15 should be immediately referred to a mental healthcare 
professional and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the investigational product.  


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5.1.8. 
Patient Health Questionnaire Depression Scale (Modified PHQ-A) 
The Modified PHQ-A Assessment (Appendix 3) will be completed by adolescent subjects 
(12-17 years old, inclusive) according to the Schedule of Visits and Assessments (Section 1.3). 
Modified PHQ-A score is the sum of the responses for the 8 questions. 
Five severity categories of depression are defined as follows: 
• None - Minimal depression (0 to 4) 
• Mild depression (5 to 9) 
• Moderate depression (10 to 14) 
• Moderately severe depression (15 to 19) 
• Severe depression (20 to 24) 
Subjects with a modified PHQ-A score of 10-14 should be referred to a mental health 
professional for evaluation, regardless of the reason for their change in score.  
Subjects with a modified PHQ-A score ≥15 should be immediately referred to a mental health 
professional, and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the investigational product.  
5.1.9. 
Columbia-Suicide Severity Rating Scale (C-SSRS) 
C-SSRS Assessments will be performed according to the Schedule of Visits and Assessments 
(Section 1.3). 
The administration schedule of the C-SSRS will be: 
• The Baseline-Screening version (Appendix 4) will be used at Screening to provide a 
pre-treatment assessment Baseline. The timeframe for the Baseline-Screening version 
is the past 6 months for suicidal ideation and past 5 years for suicidal behavior. 
• On all subsequent visits, the Since Last Visit version (Appendix 5) will be used.  
• A score greater than 0 at the Screening or Baseline visit in suicidal ideation may 
indicate the need for mental health intervention. The Investigator should not enroll 
the subject in the study. 
• Any score greater than 0 in the suicidal ideation score may indicate the need for 
mental health intervention. The Investigator should give consideration for the subject 
to discontinue from the IP and prompt referral to a mental health professional and/or 
possibly the emergency room. The Medical Monitor should be contacted. 
The C-SSRS administrator will be trained via C-SSRS training video. A training certificate for 
the administrator(s) will be on file in the trial master file at the site. 
The Investigator must review the completed C-SSRS. A qualified mental health care provider 
must be available, immediately if needed, to refer the subject for further evaluation. 




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5.1.11. 
Adverse Events 
Adverse events (AEs) will be collected and assessed throughout the study according to the 
Schedule of Visits and Assessments (Section 1.3). The Investigator is responsible for ensuring 
that all adverse events observed by the clinical staff or reported by the subject that occur after the 
first application of investigational product and treated and/or followed up for up to 30 days after 
end of treatment or until the symptoms or value(s) return to the subject’s Baseline value, or 
acceptable levels, as judged by the Investigator, are recorded in the subject’s medical record and 
the eCRF. 
The Investigator is responsible for ensuring that all serious adverse events observed by the 
clinical staff or reported by the subject that occur after signing of the informed consent through 
30 days after the last day of the application of the investigational product or the end of study 
(whichever is later) are recorded in the subject’s medical record and are submitted per SAE 
reporting requirements (Section 5.7.2). 
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the Investigator and treated and/or followed up for up to 30 days after end of 
treatment or until the symptoms or value(s) return to the subject’s Baseline value, or acceptable 
levels, as judged by the Investigator. 
Refer to Section 5.7 for further details on Adverse Events. 
5.2. 
Efficacy Evaluations 
Investigators will be trained in the administration of rating scales. A training certificate is issued 
upon successful completion of the training and will be valid for 12 months, unless compliance 
issues are identified that warrant retraining. 
Note: Palms and soles may be treated with the IP in this study, but will not be counted towards 
IGA, PASI or BSA assessments. 
5.2.1. 
Scalp (S-IGA) and Body (B-IGA) Investigator Global Assessments 
Investigator Global Assessments (S-IGA and B-IGA) will be performed according to the 
Schedule of Visits and Assessments (Section 1.3). The S-IGAs should be completed prior to any 
other physician assessments. The B-IGA will be the second efficacy assessment performed at 
clinic visits (after the S-IGA).   
The IGAs are static evaluations of qualitative overall psoriasis severity. The global assessment 
scales are ordinal scales with five severity grades (reported only in integers of 0 to 4). Each grade 
is defined by a distinct and clinically relevant morphologic description that minimizes 
inter-observer variability. 
Every effort must be made for the same Evaluator to complete the S-IGA and B-IGA for 
the subject at every study visit, particularly for Baseline and Week 8. 


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5.2.1.1. 
Scalp - Investigator Global Assessment of Disease (S-IGA) 
The Scalp-IGA (S-IGA) will be the first efficacy assessment performed at clinic visits.  As 
with other efficacy assessments, the S-IGA should be performed prior to the application of 
any Investigational Product. 
Scale 
Grade 
Description 
0 
Clear  
Plaque thickening = no elevation or thickening over normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red coloration but post-inflammatory 
hyperpigmentation may be present) 
1 
Almost 
Clear 
Plaque thickening = none or possible thickening but difficult to ascertain if 
there is a slight elevation above normal skin level 
Scaling = none or residual surface drying and scaling 
Erythema = light pink coloration 
2 
Mild  
Plaque thickening = slight but definite elevation 
Scaling = fine scales partially or mostly covering the lesions 
Erythema = light red coloration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = most lesions at least partially covered 
Erythema = definite red coloration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale, covering most or all of 
lesions 
Erythema = very bright red coloration; extreme red coloration; deep red 
coloration  


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5.2.1.2. 
Body - Investigator Global Assessment of Disease (B-IGA, i.e. non-scalp) 
The Body-IGA (B-IGA) will be the second efficacy assessment performed at clinic visits 
(after the S-IGA).  As with other efficacy assessments, the B-IGA should be performed 
prior to the application of any Investigational Product.  In assessing B-IGA, the scalp, 
palms, and soles should not be considered. 
Scale 
Grade 
Description 
0 
Clear  
Plaque thickening = no elevation or thickening over normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red coloration but post-inflammatory 
hyperpigmentation may be present) 
1 
Almost 
Clear 
Plaque thickening = none or possible thickening but difficult to ascertain if 
there is a slight elevation above normal skin level 
Scaling = none or residual surface drying and scaling 
Erythema = light pink coloration 
2 
Mild  
Plaque thickening = slight but definite elevation 
Scaling = fine scales partially or mostly covering the lesions 
Erythema = light red coloration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = most lesions at least partially covered 
Erythema = definite red coloration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale, covering most or all of 
lesions 
Erythema = very bright red coloration; extreme red coloration; deep red 
coloration  
5.2.2. 
Extent of Scalp Involvement 
The extent of scalp involvement assessments will be performed according to the Schedule of 
Visits and Assessments (Section 1.3).  
The extent of scalp involvement will measure the extent of the scalp affected by psoriasis, 
expressed as the percentage of total scalp surface area. For this assessment, the subject’s thumb 
approximates 1% of the total scalp surface area. 
5.2.3. 
Body Surface Area (BSA) 
The BSA assessments will be performed according to the Schedule of Visits and Assessments 
(Section 1.3).  
The BSA affected by psoriasis 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. The 


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BSA assessment includes the scalp, but it does not include the palms and soles. The total scalp 
(ie, 100% of the total scalp surface area) can be considered to be approximately 4% BSA. 
 
5.2.4. 
Psoriasis Scalp Severity Index (PSSI) 
PSSI assessments will be performed at study visits according to the Schedule of Visits and 
Assessments (Section 1.3). 
Every effort must be made for the same Evaluator to complete the PSSI for the subject at 
every study visit. 
The PSSI is used for the measurement of severity of psoriasis.  
PSSI combines the assessment of the severity of scalp lesions and the area of scalp affected into 
a single score in the range 0 (no disease) to 72 (maximal disease). 
The extent of scalp affected is scored based on the following: 
0. 0% of involved area 
1. < 10% of involved area 
2. 10–29% of involved area 
3. 30–49% of involved area 
4. 50–69% of involved area 
5. 70–89% of involved area 
6. 90–100% of involved area 
The severity is estimated by three clinical signs: erythema (‘E’; redness), induration 
(‘T’; thickness) and desquamation (‘S’; scaling). Severity parameters are measured on a scale of 
0 to 4, from none to maximum severity possible: 
0. absent 
1. slight 
2. moderate 
3. severe 
4. severest possible 
To calculate the PSSI, the sum of the severity rating for the three main signs are multiplied with 
the numerical value of the area affected: 
PSSI = Sum of scores for erythema, induration and desquamation x involved area (range 0–72) 
5.2.5. 
Psoriasis Area and Severity Index (PASI) 
Assessments will be performed as single assessments at each timepoint, from which PASI will 
be calculated. 
PASI assessments will be performed at study visits according to the Schedule of Visits and 
Assessments (Section 1.3). 


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Every effort must be made for the same Evaluator to complete the PASI for the subject at 
every study visit. 
Psoriasis Area and Severity Index (PASI) is used for the measurement of severity of psoriasis.  
PASI combines the assessment of the severity of lesions and the area affected into a single score 
in the range 0 (no disease) to 72 (maximal disease). 
The body is divided into four sections (head (h) (10% of a person's skin); arms (a) (20%); 
trunk (t) (30%); legs (l) (40%)). Each of these areas is scored by itself, and then the four scores 
are combined into the final PASI. For each section, the percent of area (A) of skin involved is 
estimated and then transformed into a grade from 0 to 6 (A): 
0. 0% of involved area 
1. < 10% of involved area 
2. 10–29% of involved area 
3. 30–49% of involved area 
4. 50–69% of involved area 
5. 70–89% of involved area 
6. 90–100% of involved area 
Note: Palms and soles may be treated with the IP in this study, but will not be counted towards 
IGA, PASI or BSA assessments. 
Within each area, the severity is estimated by three clinical signs: erythema (‘E’; redness), 
induration (‘T’; thickness) and desquamation (‘S’; scaling). Severity parameters are measured on 
a scale of 0 to 4, from none to maximum severity possible. 
To calculate the PASI, the sum of the severity rating for the three main signs are multiplied with 
the numerical value of the area affected and with the various percentages of the four body areas. 
These values are then added to complete the formula as follows: 
PASI = 0.1 (Eh + Th + Sh) Ah + 0.2 (Ea + Ta + Sa) Aa + 0.3 (Et + Tt + St)  
At + 0.4 (El + Tl + Sl) Al 
5.2.6. 
Scalp Itch-NRS (SI-NRS) 
The Scalp Itch-NRS is a single-item scale to assess the patient-reported severity of their 
symptom at the highest intensity of scalp itching over the past 24 hours. Scalp Itch-NRS will be 
determined by asking the subject’s assessment of worst itching of the scalp over the past 
24 hours. The scale is from ‘0’ to ‘10’ (‘no scalp itch’ to ‘worst scalp itch imaginable’). Subjects 
will complete the Scalp Itch-NRS assessment (Wang 2019). 
SI-NRS Assessment will be performed by subjects daily at home according to the Schedule of 
Visits and Assessments (Section 1.3) starting 7 days prior to the scheduled Baseline/Day 1 visit 
up to the Week 8/Day 57 visit.  
 


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The SI-NRS should be completed first and then WI-NRS. 
 
 
 
5.2.7. 
Worst Itch-Numerical Rating Scale (WI-NRS) 
Given that itch is an important symptom of psoriasis, a WI-NRS assessment is included in the 
present study.  The WI-NRS has been described as optimal for demonstrating a level of clinically 
meaningful improvement in itch severity in other skin conditions, including other forms of 
eczema (Yosipovitch 2019) and psoriasis (Kimball 2016). 
WI-NRS Assessment will be performed by subjects daily at home according to the Schedule of 
Visits and Assessments (Section 1.3) starting 7 days prior to the scheduled Baseline/Day 1 visit 
up to the Week 8/Day 57 visit.  
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”). Subjects will be 
asked on a scale of 0 to 10, with 0 being “no itch” and 10 being “worst itch imaginable”, how 
would you rate your itch at the worst moment during the previous 24 hours? 
 
5.2.8. 
Psoriasis Symptom Diary (PSD) 
The PSD will be performed at study visits according to the Schedule of Visits and Assessments 
(Section 1.3). The PSD includes items related to Itching (question 1), Pain (question 9) and 
Scaling (question 11). 
Only adult subjects will complete the PSD. See Appendix 6 for the PSD. 
5.2.9. 
Scalpdex 
The Scalpdex (Appendix 7) will be performed by subjects according to the Schedule of Visits 
and Assessments (Section 1.3). 




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5.6. 
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. 
The following information will be collected for all subjects: 
• Concomitant medications/procedures 
• AEs 
5.7. 
Adverse Events 
5.7.1. 
Adverse Event Definition 
An AE is defined as 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 an investigational product, whether or not related to the investigational 
product. 
The definition of AEs includes worsening of a pre-existing medical condition.  Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome.  When recording such events, provide 
descriptions that the pre-existing condition has changed (e.g., worsening hypertension for a 
subject with pre-existing hypertension).  A pre-existing condition that has not worsened during 
the study or involves an intervention, such as elective cosmetic surgery or a medical procedure 
while on study, is not considered an AE. 
Progression of treatment indication including new or worsening of anticipated clinical signs or 
symptoms, which are collected as clinical efficacy variables and assessed as unequivocally 
associated with the disease progression and /or lack of efficacy, should NOT be reported as 
adverse events unless the disease progression is greater than anticipated in the natural course of 
the disease.  
In general, abnormal laboratory findings without clinical significance (based on the 
Investigator’s judgment) are not to be recorded as AEs.  However, abnormal laboratory findings 
that result in new or worsening clinical sequelae, or that require therapy or adjustment in current 
therapy, are considered AEs.  Where applicable, clinical sequelae (not the laboratory 
abnormality) are to be recorded as the AE. 
5.7.2. 
Serious Adverse Event 
The definitions and reporting requirements of the Food and Drug Administration (FDA)/ICH 
Guidelines for Clinical Safety Data Management, Definitions and Standards for Expedited 
Reporting, Topic E2A will be adhered to.  Mandatory reporting of all serious unexpected adverse 
drug reactions (SUSARs) to Health Canada [as per C.05.014 (1) of the FDR] will be adhered. If 
any AEs are serious, as defined by ICH Guidelines for Clinical Safety, required procedures will 
be followed. 


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An SAE is defined as any AE that, in the view of either the PI or Sponsor, meets at least 1 of the 
following serious criteria: 
• Fatal 
• Life-threatening (places the subject at immediate risk of death) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant incapacity/disability 
• Congenital anomaly/birth defect 
• Other important medical events that, based upon appropriate medical judgment, may 
jeopardize the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed in the above definition 
Hospitalization does not include the following: 
• Rehabilitation facilities, hospice facilities or respite care (e.g., caregiver relief) 
• Nursing homes or skilled nursing facilities 
• Emergency department 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 Baseline 
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 Investigator Brochure (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 study documentation.  


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5.7.3. 
Suspected Unexpected Serious Adverse Reaction (SUSAR) 
SUSAR 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. 
5.7.4. 
Safety Review with Subject 
At each subsequent clinic visit after the Screening 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. 
5.7.5. 
Adverse Event Reporting 
The Investigator is responsible for recording all adverse events, observed by the clinic staff, or 
reported by the subject that occur after the first application of investigational product through 
30 days after end of treatment are recorded in the subject’s medical record and the eCRF.  
Serious adverse events observed by the clinic staff or reported by the subject after signing the 
informed consent form will be recorded.  
All adverse events that meet the criteria for “serious” (i.e., SAEs) will be reported to the Sponsor 
via fax or e-mail to
.com 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 Institutional Review Board (IRB) will be notified of the Alert Reports as per FDA, ICH and 
the IRB’s policies and procedures. 
The Sponsor, or delegate, will be responsible for reporting SAEs to health authorities per local 
reporting requirements. The Investigator will be responsible for reporting events to their 
respective IRBs/ Ethics Review Board (ERB) in accordance with the IRB/ERB requirements. 
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 for 30 days after end of treatment until 
the symptoms or value(s) return to the subject’s Baseline value, or acceptable levels, as judged 
by the Investigator. Where appropriate, medical test(s) and/or examination(s) will be performed 
to document resolution of event(s).  
The Investigator will review each adverse event and assess its relationship to Investigational 
Product (unrelated, unlikely, possibly, probably, likely). Each sign or symptom reported will be 
graded on the NIH NCI CTCAE 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) of 
each event will be noted. 


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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 an 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. 
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. 
 


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Footnotes from table above: 
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. 
5.8. 
Reporting Pregnancy 
During study participation, 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. 
The Investigator is responsible for reporting all available pregnancy information on the 
pregnancy report to 
 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. In addition, 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. 
Partner pregnancies of a male subject do not need to be reported. 
5.9. 
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 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) laboratory abnormality (confirmed by repeat 
sample) which in the opinion of the Principal Investigator or Medical Monitor 
warrants discontinuation from the study for that subject’s well-being  
A subject with a PHQ-8/PHQ-A score ≥15 should receive immediate referral to a mental health 
care professional, and Investigators in consultation with the mental health professional should 
consider interruption or discontinuation of the investigational product. 


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• Subjects with a PHQ-8 or modified PHQ-A score of 10-14 should be referred to a 
mental health professional for evaluation, regardless of the reason for their change in 
score 
A subject that is experiencing suicidal ideation and behavior should be referred immediately to a 
qualified mental health care provider and consideration given to discontinuation from IP. 
As noted above, IP must be discontinued immediately in the event of a female subject’s 
pregnancy. 
IP 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. 
IP Treatment should be discontinued: 
• If the reaction reoccurs. IP should be discontinued permanently, and the subject 
followed until the reaction resolves. 
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. 
In the event of a medical emergency where unblinding is required to provide medical care to the 
subject, refer to the most current IWRS Plan and Breaking Treatment Codes (Section 4.8.5). 
Contact the Medical Monitor and the Sponsor promptly. 
6. 
DATA ANALYSIS 
Data will be handled and processed according to the Contract Research Organization’s (CRO) 
Standard Operating Procedures, which are written based on the principles of GCP. 
6.1. 
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 or later) unless otherwise 
stated. 
Subjects will be stratified by study site, Baseline S-IGA (3 vs. 4), and Baseline B-IGA (2 vs. ≥3).   


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6.1.1. 
Determination of Sample Size 
A sample size of up to approximately 420 subjects is planned for the study. 
The randomization scheme will be 2:1 (ARQ-154 foam 0.3% QD: matching vehicle QD). 
Approximately 280 subjects will receive ARQ-154 foam 0.3% QD; approximately 140 subjects 
will receive vehicle foam QD.  
This sample size provides more than 99% power to detect an overall 35% difference between 
treatment groups on S-IGA success at Week 8 and an overall 25% difference between treatment 
groups on B-IGA success at Week 8 at α=0.025 using a 2-sided stratified (B-IGA at 
randomization, S-IGA at randomization and study site) Cochran-Mantel-Haenszel test.  The 
results from a recent phase 2 study (ARQ‑154-204) of ARQ-154 foam 0.3% compared to vehicle 
treatment were used to estimate the treatment difference.   
The number of subjects to be enrolled will also provide at least 90% power for most of the 
secondary endpoint analyses.  Additionally, the larger study size is included in order to provide 
additional/sufficient numbers of subjects on ARQ-154 treatment for a safety database. 
6.1.2. 
Interim Analysis 
No interim analyses are planned.  
6.1.3. 
Background and Demographic Characteristics 
Descriptive statistics will be presented for the subject disposition, demographics, Baseline 
characteristics, treatment compliance, efficacy endpoints and safety data collected in the clinical 
study. This includes the number and percentage of subjects for binary endpoints/categorical data, 
and mean, SD, median, Q1, Q3, minimum, and maximum for continuous data.  
6.1.4. 
Study Disposition 
Number of subjects randomized, receiving IP, completing study, and withdrawing prematurely 
(with reason for withdrawal) will be summarized by treatment group. 
6.1.5. 
Protocol Deviations and Eligibility Deviations 
The number of subjects with important protocol deviations and/or eligibility deviations will be 
summarized in categories by treatment group. 
6.1.6. 
Investigational Product Application 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 can weight will be summarized by treatment 
using descriptive statistics. 
IP dose compliance will be calculated based on number of applications divided by the expected 
number (amount) of IP applications for each subject.  Compliance will be summarized 
descriptively by treatment group.  Amount of IP (weight) used will also be summarized. 






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Family 1 (α=0.01 or α = 0.015): 
• For subjects with Baseline Scalp Itch (SI) NRS score ≥4, achievement of ≥4-point 
improvement from Baseline in SI-NRS at Week 8 (“SI-NRS Success at Week 8”) 
• SI-NRS Success at Week 4 
• SI-NRS Success at Week 2 
• SI-NRS Change from Baseline (CFB) at Week 1 
• SI-NRS CFB at 72 hours 
Family 2 (α=0.005): 
• For subjects with Baseline WI-NRS score ≥4, achievement of ≥4-point improvement 
from Baseline in WI-NRS at Week 8 (“WI-NRS Success at Week 8”) 
• PASI-75 at Week 8 
• CFB in PSD Items related to Itching, Pain, and Scaling (Questions 1, 9, and 11) 
aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• PSSI-75 at Week 8 
Family 3 (α=0.01 or 0.015 or 0.025): 
• S-IGA score of ‘clear’ at Week 8 
• S-IGA Success at Week 4 
• CFB in PASI at Week 2 
• S-IGA Success at Week 2 
• PSD Total Score = 0 at Week 8  
• SI-NRS CFB at Day 1 
The Fallback Method will be used to pass unused alpha across the Families.  The Families will 
be tested in this order:  Family 2, Family 1, Family 3.   Testing will be sequential within Family 
2 and Family 1, with the order of testing of each endpoint within each family as listed above.   
Testing within Family 3 will be implemented with Holm’s procedure.   
To start, Family 2 will be tested, sequentially within Family 2, each endpoint at the α=0.005 
level.  Should the testing succeed through all seven endpoints in Family 2, the α=0.005 will 
remain unused, and will be passed to Family 1.  


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The testing of the five SI-NRS endpoints in Family 1 will be sequential, either at the α=0.01 
level (assumes Family 2 had an unsuccessful test), or the α=0.015 level (assumes all endpoints in 
Family 2 were successful at the α=0.005 level). 
Family 3 contains six endpoints.  Family 3 has initially been allocated α=0.01.  This creates three 
possible testing alpha levels for the Family 3 endpoints:   
• If all tests in Family 1 (α=0.01) and Family 2 (α=0.005) are successful, then 
α=0.005+0.01=0.015 is unused, and the α=0.015 will be carried to Family 3, allowing 
Family 3 endpoints to be tested at the full 0.025 level. 
• If the α=0.005 in Family 2 is used, but the subsequent α=0.01 allocated to Family 1 is not 
used, then Family 3 endpoints will be tested at the α=0.01+0.01=0.02 level. 
• If the α=0.01 in Family 1 is used, and the α=0.005 in Family 2 is also used, then Family 3 
endpoints will be tested at α=0.01. 
 
Descriptive statistics will be presented for endpoint and safety data collected in the clinical 
study. This includes the number and percentage of subjects for binary endpoints/categorical data, 
and mean, SD, median, Q1, Q3, minimum, and maximum for continuous data.   
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 by preferred term, system organ class, and treatment 
group 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 and percent 
changes from Baseline in laboratory values and vital signs will also be summarized by visit. In 
addition, changes from Baseline and percent changes from Baseline in weight and laboratory 
values will be summarized using shift tables.  
Descriptive statistics will be calculated for the PHQ-8 (adults) and Modified PHQ-A 
(adolescents). The C-SSRS will be analyzed per the Scoring and Data Analysis Guide from the 
Columbia Lighthouse Project. 
7. 
STUDY ADMINISTRATION 
7.1. 
Ethics 
7.1.1. 
Ethics Review Board 
Before screening of subjects into the study, the current protocol, ICF/assent, and any 
accompanying material to be provided to the subjects will be reviewed and approved by an 
appropriate IRB/ERB, as required by FDA (21 CFR § 56) or Health Canada and ICH GCP 
regulations.  A letter documenting the IRB approval must be received by the Sponsor before the 


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initiation of the study at a study 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. However, the frequency of these reports will depend on IRB requirements. As soon as 
possible after completion or termination of the study, the Investigator will submit a final report to 
the IRB per the IRB requirements, and in compliance with FDA and ICH GCP guidelines. 
The Investigator, Sponsor, or designee shall promptly notify the IRB of any SAEs, SUSARs, or 
any other information that may affect the safe use of the study drug(s) during the study, per the 
IRB local requirements, and in compliance with FDA regulations and ICH GCP guidelines. 
7.1.2. 
Ethical Conduct of the Study 
This research will be conducted in accordance with the protocol, the principles of the 
Tri-Council Policy Statement, the ethical principles set forth in the Declaration of Helsinki, and 
the ICH harmonized tripartite guideline regarding GCP (E6 (R2), December 2016). 
7.1.3. 
Subject Information and Consent/Assent 
The Investigator is responsible for obtaining written informed consent or assent (for adolescents) 
from everyone participating in this study after adequate explanation (in non-technical terms) of 
the aims, methods, objectives, and potential hazards of the study and before undertaking any 
study-related procedures. The Investigator must use the most current IRB or ERB-approved 
consent/assent forms for documenting written informed consent and assent (for adolescents). 
Subjects will be assured that they may withdraw from the study at any time without jeopardizing 
their medical care. Each informed consent (or assent as applicable) will be read, appropriately 
signed, and dated by the subject or the subject’s legally authorized representative and the person 
conducting the consent discussion, and by an impartial witness if required by the IRB/ERB local 
requirements. 
Subjects will be given a copy of their ICF/assent. 
7.2. 
Study Completion and Termination 
7.2.1. 
Study Completion 
The study is considered completed with the last visit of the last subject participating in the study. 
The final data from the study 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. 
7.2.2. 
Study Termination 
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A 
study 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 a study 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 drug development. 
7.3. 
Study Monitoring 
Prior to the initiation of the clinical investigation, Sponsor representatives or designees may visit 
the study site where the investigation is to be conducted.  Sponsor representatives or designees 
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 or designees will also visit the study site at 
appropriate intervals as required to ensure compliance with the protocol and to verify the 
accuracy and completeness of data reported on the eCRFs.  The Study Director or designees shall 
be available for consultation with the Investigator and serve as liaisons between the study 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. 
7.4. 
Data Quality Assurance 
To ensure the collection of adequate, consistent, complete, and reliable data during this clinical 
investigation, Sponsor representatives or designees may conduct audits of participating sites at 
appropriate intervals throughout the study.  The results of these periodic site audits may be 
subject to review by independent auditors at completion of the clinical investigation. 
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. 
7.5. 
Data Handling and Record Keeping 
During the clinical study, the Investigator will maintain adequate source records, including 
medical records, records detailing the progress of the study for each subject, laboratory reports, 
signed informed consent/assent forms, IP disposition records, correspondence with the IRB or 
IEC and Study Monitor/Sponsor, AE reports, and information regarding subject discontinuation 
and completion of the clinical study. 


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All required study data will be recorded on eCRFs. 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 IP.  If this requirement differs from any local regulations, the local 
regulations will take precedence unless the local retention policy is less than 2 years. 
7.6. 
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)/IEC(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/IEC, 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)/IEC(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. 
7.7. 
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. 
The Investigator agrees that all information received from Arcutis Biotherapeutics Inc., including 
but not limited to the IB, this protocol, 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. 


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7.8. 
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. 
Any change to the Investigator’s financial interest during the study and up to one year after study 
completion will be reported to the Sponsor. 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. 
7.9. 
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). 
7.10. 
Publication Policy 
The Sponsor is supportive of publishing clinical study 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. 
 
 


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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. 
Blakely K, Gooderham M. Management of scalp psoriasis: current perspectives. Psoriasis 
(Auckl). 2016;6:33-40. Published 2016 Mar 29. Doi: 10.2147/PTT.S85330. 
Brion DE, Raynaud F, Plet A, et al.  Deficiency of cyclic AMP dependent protein kinases in 
human psoriasis.  Proc. Natl. Acad. Sci. 1986;83:5272-5276. 
DALIRESP (roflumilast) tablets [package insert]. AstraZeneca Pharmaceuticals LP, Wilmington, 
DE USA; 2018. 
DAXAS (roflumilast) film-coated tablets [product monograph]. AstraZeneca Canada, Inc., 
Mississauga, Ontario Canada; 2017. 
Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast – a 
selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary 
disease. Pulm Pharmacol Ther. 2010;23:235–256. 
Investigator’s Brochure, Edition 4.0, 22 January 2021. 
Kimball AB, Naegeli AN, Edson-Heredia E, et al. Psychometric properties of the Itch Numeric 
Rating Scale in patients with moderate-to-severe plaque psoriasis. Br. J. Dermatol. 
2016;175(1):157-162. doi:10.1111/bjd.1446. 
Kivelevitch D, Frieder J, Watson I, et al. Pharmacotherapeutic approaches for treating psoriasis 
in difficult-to-treat areas. Expert Opin Pharmacother. 2018;19(6):561-575. 
Merola JF, Qureshi A, Husni ME. Underdiagnosed and undertreated psoriasis: Nuances of 
treating psoriasis affecting the scalp, face, intertriginous areas, genitals, hands, feet, and nails. 
Dermatol Ther. 2018;31(3):e12589. 
Naegeli AN, 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;54(6):715–22. 
OTEZLA® (apremilast) tablets, for oral use [package insert].  Celgene Corporation, Summit, NJ 
USA; 2017. 
Schlager JG, Rosumeck S, Werner RN, et al. Topical treatments for scalp psoriasis: summary of 
a Cochrane Systematic Review. Br. J. Dermatol. 2016;176(3):604-614. 
Wang TS, Tsai TF. Managing Scalp Psoriasis: An Evidence-Based Review. Am J Clin Dermatol. 
2017;18(1):17-43. 
Wang Y, Coyne K, Sofen H, et al. Qualitative analysis and reproducibility assessment of the 
Scalp Itch Numeric Rating Scale among patients with moderate to severe plaque psoriasis of the 
scalp. Journal of Dermatological Treatment. 2019. DOI: 10.1080/09546634.2019.1577546. 
Yosipovitch, G, et al. Peak Pruritis Numerical Rating Scale: psychometric validation and 
responder definition for assessing itch in moderate-to-severe atopic dermatitis. Br J Dermatol.  
2019;181(4):761-769. doi:10.1111/bjd.17744. 


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9. 
APPENDICES 
APPENDIX 1. BODY & SCALP DIAGRAM 
Site personnel to mark treatable areas identified by the Investigator. 
Reminder: Application will be all areas affected including scalp, face, trunk and/or 
intertriginous/genital regions. Subject should continue to apply even if area(s) clears and treat 
new lesions. 
 
 
 
 
 
 
 


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APPENDIX 2. PATIENT HEALTH QUESTIONNAIRE 
DEPRESSION SCALE (PHQ-8) 
 


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APPENDIX 3. MODIFIED PATIENT HEALTH 
QUESTIONNAIRE DEPRESSION SCALE (PHQ-A) 
 


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APPENDIX 4. COLUMBIA-SUICIDE SEVERITY RATING 
SCALE (C--SSRS) BASELINE/SCREENING VERSION 
 
Please note: The timeframe for the Baseline-Screening version is the past 6 months 
for suicidal ideation and past 5 years for suicidal behavior. 


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APPENDIX 5. COLUMBIA-SUICIDE SEVERITY RATING SCALE 
(C-SSRS) SINCE LAST VISIT VERSION 
 


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APPENDIX 6. PSORIASIS SYMPTOM DIARY 
 
  
 
 Psoriasis Symptom Diary (PSD) 
 
 
 
 
 
 1 Overall, how severe was 
your psoriasis-related 
itching over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
 No itching 
Itching as bad as you  
can imagine 
 
  
 
 
2 Overall, how bothered  
were you by your psoriasis-
related itching over the 
past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 3 Overall, how severe was 
your psoriasis-related 
stinging over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
No stinging 
Stinging as bad as you  
can imagine 
 
  
 
 4 Overall, how bothered  
were you by your psoriasis-
related stinging over the 
past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 5 Overall, how severe was 
your psoriasis-related 
burning over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
No burning 
Burning as bad as you  
can imagine 
 
 
 
 
 
 


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 6 Overall, how bothered  
were you by your psoriasis-
related burning over the 
past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 7 Overall, how severe was 
your psoriasis-affected skin 
cracking over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
 No pain 
Pain as bad as you  
can imagine 
 
  
 
 8 Overall, how bothered  
were you by your psoriasis-
affected skin cracking over 
the past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 9 Overall, how severe was 
your psoriasis-related pain 
over the past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
No pain 
Pain as bad as you  
can imagine 
 
  
 
 10 Overall, how bothered  
were you by your psoriasis-
related pain over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 11 Overall, how severe was 
your psoriasis scaling over 
the past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
No scaling  
Scaling as bad as you  
can imagine 
 
 
 
 
 
 
 
 


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 12 Overall, how bothered were 
you by your psoriasis 
scaling over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not bothered  
at all 
As bothered as you  
can imagine 
 
  
 
 13 Overall, how noticeable did 
you think the color of your 
psoriasis-affected skin was 
over the past 24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Not at all  
noticeable 
As noticeable as you  
can imagine 
 
  
 
 14 Overall, how much did you 
try to hide your psoriasis-
affected skin over the past 
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
Did not try to  
hide at all 
Totally avoided being seen 
by others 
 
  
 
 15 Overall, how much did  
your psoriasis cause you  
to avoid activities with other 
people over the past  
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
You did not avoid  
other people  
Avoided other people as 
much as you ever have 
 
  
 
 16 Overall, how embarrassed 
were you because of your 
psoriasis over the past  
24 hours? 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10   
 
No embarrassment 
As embarrassed as you  
can imagine 
 
  
 
 
 
 
 
 
 
 
 
© Novartis 2018 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 78 of 85 
 
 
  
 
APPENDIX 7. SCALPDEX 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 79 of 85 
 
 
  
 
APPENDIX 8. DERMATOLOGY LIFE QUALITY INDEX (DLQI) 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 80 of 85 
 
 
  
 
 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 81 of 85 
 
 
  
 
APPENDIX 9. CHILDREN’S DERMATOLOGY LIFE QUALITY 
INDEX (CDLQI) 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 82 of 85 
 
 
  
 
 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 83 of 85 
 
 
  
 
APPENDIX 10. COVID-19 STUDY SITE GUIDANCE 
BACKGROUND 
As the impact of coronavirus disease 2019 (COVID-19) continues to develop, Premier Research 
Inc. and Arcutis Biotherapeutics Inc. have collated the following guidelines in response for study 
sites participating in the ARQ-154-309. While it is ideal for subjects to perform all 
protocol-specific assessments at the study site, both Premier and Arcutis are focused on 
prioritizing subject safety and data integrity. Therefore, the following guidelines will identify 
challenges and mitigation strategies while operating clinical trials remotely. 
REMOTE DATA COLLECTION 
In the event subjects are unable to complete protocol-specific assessments onsite, study sites may 
collect data from subjects remotely via telephone and/or by traditional mail or email. The method 
used for data collection must be clearly documented in the source. Whenever possible, sites 
should adhere to the protocol visit window for remote data collection. Screening and Baseline 
(Day 1) visits/assessments must be performed in the clinic and must NOT be completed 
remotely. If necessary, these visits can be delayed ensuring they are conducted in the clinic and 
not remotely. 
Data collection by phone may be performed. Subjects are contacted via telephone and site staff 
will collect data verbally for all critical data points applicable. Subject responses should be 
recorded in the site source documents. Data collected remotely should be entered into the 
Electronic Data Capture (EDC) system (iMedidata Rave). 
Data collection by mail or email may also be performed for applicable assessments. Site staff 
will contact subjects via traditional mail or email to collect data using paper versions of study 
questionnaires. C-SSRS cannot be collected by mail/email as this requires subject interview by 
site staff. 
Investigator assessments and subject questionnaires normally completed during on-site visits 
should be completed on the appropriate paper source documents and entered in the EDC. The 
following subject assessments/questionnaires are approved to be collected via 
telemedicine/remotely: 
• C-SSRS 
• WI-NRS/SI-NRS 
• PHQ-8/PHQ-A 
• Subject Local Tolerability 
• Adverse Events 
• Concomitant medication 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 84 of 85 
 
 
  
 
The following Investigator assessments cannot be completed via telemedicine/remotely: 
• S-IGA  
• B-IGA 
• PASI 
• PSSI 
• BSA 
• Investigator Local Tolerability 
• Subject Weight 
GUIDELINES FOR REMOTE DATA COLLECTION 
1. Highest priorities: the subject safety and preserving integrity of data are critical 
2. 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 IRB and Sponsor (via reporting to your site assigned CRA). All protocol deviations 
which occurred as a result of COVID-19 disruptions (e.g., visits out of window, missed 
assessments, etc.) should be differentiated from other PDs. It is prudent to receive IRB 
guidance or approval if a deviation is known to occur in advance (i.e., extending IP 
application or changing assessment windows, etc.). 
3. If, despite all efforts, a planned clinic visit is absolutely not possible due to a COVID-19 
related issue (e.g., site has closed, subject prohibited from coming to the study site, etc.), 
Sponsor’s strong preference is a delayed clinic visit. If the subject can come to clinic 
within a reasonable amount of time considering the protocol allowed visit window. If a 
delayed clinic visit cannot be completed within 14 days of the protocol specified visit 
window, please contact the Medical Monitor for additional guidance. 
4. It is critical to ensure subjects have enough IP in the event timely clinic visit(s) is/are not 
possible. It is also critical to ensure subjects are instructed to continue to apply IP per 
protocol for the duration of their participation in the study. Subjects should also be 
reminded to complete their daily diaries and IP compliance should be assessed via phone 
if clinic visits are not possible or are delayed. 
5. It is critical for preserving data integrity to make every effort possible to have a subject 
return to clinic for the Week 8 visit. For visits conducted in the clinic, it is critical to 
ensure Rater consistency for all efficacy assessments (e.g., IGA, etc.). If absolutely 
necessary, it is preferred to have several missed visits and a delayed Week 8 visit versus 
having no Week 8 visit. If it is not possible for a subject to return on-site within window 
for the Week 8 visit, sites should: 
a. Ensure the subject has signed the most current IRB approved ICF. 
b. Contact subjects to discuss continue administration of IP and continue to complete 
their dosing diaries per regular IP administration instructions. 


Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
Confidential 
Page 85 of 85 
 
 
  
 
c. Subjects are approved to continue applying IP post Week 8 as long as the following 
have been discussed with the subject: 
− Site should confirm the subject has adequate IP to continue dosing and if not ask 
the subject to return to the site to pick up additional IP or refer to the current IP 
Handling Plan for instructions on shipment of IP from site to subject. 
− Confirm the subject has no AEs that would warrant discontinuation of the IP. 
− Site should discuss any new or ongoing conmed(s) and determine if the use of any 
warrant having the subject stop IP application or not. 
− For any female subject of childbearing potential the site should discuss and 
confirm the subject has continued her methods of ensuring pregnancy does not 
occur. Any deviation from these methods should be discussed further and the site 
should determine if IP should be halted or contact the medical monitor or Arcutis 
if they have any questions.  A urine pregnancy test should be performed at the 
next onsite visit (this is applicable to prior visits being missed due to COVID-19 
as well). 
− Subjects are approved to continue dosing for up to 14 days past their Week 8 visit. 
After this, sites should reach out to the Medical Monitor and/or Arcutis directly 
for approval to have subjects continue dosing. 
− All the above discussions must be documented in the source. 
d. If available, home health nurse visits could be considered for collection of Vital Signs 
and Clinical Labs. 
e. In the event a subject is quarantined, has symptoms, or is confirmed positive for 
COVID-19, it is the Sponsor’s opinion that IP can continue, assuming no other 
contraindications.  
 

SAP_001.pdf: 
 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 1 of 63 
   Statistical Analysis Plan 
Sponsor: 
Arcutis Biotherapeutics, Inc. 
Protocol Title: 
A Phase 3, 8-Week, Parallel Group, Double Blind, 
Vehicle-Controlled Study of the Safety and Efficacy of 
ARQ-154 Foam 0.3% Administered QD in Subjects with 
Scalp and Body Psoriasis (ARRECTOR) 
Protocol Number: 
ARQ-154-309 
Premier Research PCN: 
ARCU214118 
Document Version: 
Final 3.0 
Document Date 
08-Nov-2022 
 
 
 
 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 2 of 63 
APPROVALS 
Role 
Signatures 
Date (dd-Mmm-yyyy) 
Biostatistician 
Print Name 
 
Sign Name: 
 
 
 
 
 
Premier Senior 
Reviewer 
Print Name:  
 
Sign Name: 
 
 
 
 
 
Arcutis 
Biotherapeutics, 
Inc. 
Representative 
Print Name:  
 
Sign Name: 
 
 
 
 
 
 
Arcutis 
Biotherapeutics, 
Inc. 
Representative 
Print Name:  
 
Sign Name: 
 
 
 
 
 
 
 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 3 of 63 
DOCUMENT HISTORY 
 
Final V1.0 
31-May-2022 – Initial version. 
Final V2.0 
11-Aug-2022 –  
1. Synopsis, Sections 2.2.2.2, 6.1.3, 8.2.4, and Table 5:   
a. Replace the change from baseline in PSD total score at Weeks 2, 
4, and 8 in the list of secondary efficacy endpoints within Family 
2 with the endpoints listed below to be consistent with Protocol 
Amendment 3: 
i.  CFB in PSD Items related to Itching, Pain, and Scaling 
(Questions 1, 9, and 11) aggregate score at Week 8 
ii. PSD Item related to Itching (Question 1) = 0 at Week 8 
iii. PSD Item related to Scaling (Question 11) = 0 at Week 8 
iv. PSD Item related to Pain (Question 9) = 0 at Week 8 
b. Add PSD Total score = 0 to the list of endpoints in Family 3 to 
be consistent with changes in Protocol Amendment 3.  
c. Moved SI-NRS CFB at Day 1 from Family 1 to Family 3 to be 
consistent with changes in Protocol Amendment 3  
2. Sections 2.2.2.3 and 8.3:  
a. Remove S-IGA score of Clear or Almost Clear because it would 
be redundant to the definition of S-IGA Success as subjects 
enrolled should have baseline S-IGA score of at least 3 
b. Re-classify change from baseline in PSD total score at Weeks 2, 
4, and 8 as an other efficacy endpoint 
c. Add B-IGA success at Weeks 2 and 4 as an other efficacy 
endpoint 
d. Add additional endpoints related to the new endpoints identified 
in 1.a.i-iv and 1.b above 
e. Add the Scalpdex emotion, function, and symptom scales  
3. Table 6: Added to clarify the analyses completed for each of the other 
efficacy endpoints 
4. Section 6.1.6: Removed “in each strata combination” as it is not 
intended nor feasible to have a subject in each strata combination. 
5. Sections 6.1.2, 6.1.4.1, and 8: Clarify the intention to use S-IGA and B-
IGA strata, not the actual value, used per randomization in the analysis 
models defined in PROC FREQ and PROC MIXED. 
6. Section 6.1.1: Clarified that values collected with the same start date 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
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and time as the start of study drug application can be used as baseline. 
7. Section 6.1.5.2 Table 3: Correct typographical error in Table regarding 
days to use for weekly average baseline score. 
Final V3.0 
This was a post-database lock and post-unblinding update to the SAP.  The 
purpose is to clarify that for subjects who discontinued early from the study due to 
adverse event or lack of efficacy, a subject will be considered as non-responder (for MI 
and nonresponder imputation analyses) or missing (for observed case analyses) for all 
analysis visits (refer to Section 5.4) on or after the associated analysis visit of the 
subject’s last dose day (refer to Section 6.1.5).  This change to the primary estimand 
and multiple imputation procedure was based on recommendations from FDA 
during a pre-NDA meeting for a similar program held on 9/14/2022. 
 
 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 5 of 63 
TABLE OF CONTENTS 
1. 
OVERVIEW ..................................................................................................................... 11 
2. 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 12 
2.1. 
Study Objectives ......................................................................................................... 12 
2.1.1. Primary Objective ....................................................................................................... 12 
2.2. 
Study Endpoints .......................................................................................................... 12 
2.2.1. Safety Endpoints ......................................................................................................... 12 
2.2.2. Efficacy Endpoints ...................................................................................................... 12 
3. 
OVERALL STUDY DESIGN AND PLAN ..................................................................... 15 
3.1. 
Overall Design ............................................................................................................ 15 
3.2. 
Sample Size and Power ............................................................................................... 15 
3.3. 
Study Population ......................................................................................................... 15 
3.4. 
Treatments Administered ............................................................................................ 16 
3.5. 
Method of Assigning Subjects to Treatment Groups .................................................. 16 
3.6. 
Blinding and Unblinding............................................................................................. 16 
3.7. 
Schedule of Events ...................................................................................................... 16 
4. 
STATISTICAL ANALYSIS AND REPORTING ........................................................... 19 
4.1. 
Introduction ................................................................................................................. 19 
4.2. 
Interim Analysis and Data Monitoring ....................................................................... 19 
5. 
ANALYSIS POPULATIONS .......................................................................................... 19 
6. 
GENERAL ISSUES FOR STATISTICAL ANALYSIS .................................................. 20 
6.1. 
Statistical Definitions and Algorithms ........................................................................ 20 
6.1.1. Baseline ....................................................................................................................... 20 
6.1.2. Adjustments for Covariates......................................................................................... 21 
6.1.3. Covariates for this study include the pooled site group (see Section 6.1.6), 
baseline S-IGA randomization strata (S-IGA = 3 vs. S-IGA =4) and baseline B-
IGA randomization strata (B-IGA = 2 vs. B-IGA ≥ 3). Multiple Comparisons ......... 21 
6.1.4. Handling of Dropouts or Missing Data ....................................................................... 22 
6.1.5. Analysis Visit Windows ............................................................................................. 26 
6.1.6. Pooling of Sites ........................................................................................................... 27 
6.1.7. Derived Variables ....................................................................................................... 27 
6.1.8. Data Adjustments/Handling/Conventions .................................................................. 31 
6.2. 
Special Handling for COVID-19 Disruptions............................................................. 32 
7. 
STUDY SUBJECTS AND DEMOGRAPHICS ............................................................... 33 
7.1. 
Disposition of Subjects and Withdrawals ................................................................... 33 
7.2. 
Protocol Deviations ..................................................................................................... 33 
7.3. 
Demographics and Other Baseline Characteristics ..................................................... 33 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 6 of 63 
7.4. 
Exposure and Compliance .......................................................................................... 34 
8. 
EFFICACY ANALYSIS .................................................................................................. 35 
8.1. 
Primary Efficacy Analyses ......................................................................................... 35 
8.1.1. Scalp Investigator Global Assessment (S-IGA) ......................................................... 37 
8.1.2. Body Investigator Global Assessment (B-IGA) ......................................................... 38 
8.1.3. Hypothesis Testing...................................................................................................... 38 
8.1.4. Sensitivity and Supplemental Analyses ...................................................................... 38 
8.1.5. Impact of Site .............................................................................................................. 39 
8.2. 
Secondary Efficacy Analyses ..................................................................................... 39 
8.2.1. Scalp Itch – Numeric Rating Scale (SI-NRS) ............................................................. 39 
8.2.2. Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score................................... 40 
8.2.3. Psoriasis Area and Severity Index (PASI) .................................................................. 40 
8.2.4. Psoriasis Symptoms Diary (PSD) ............................................................................... 41 
8.2.5. Psoriasis Scalp Severity Index (PSSI) ........................................................................ 41 
8.2.6. Scalp Investigator Global Assessment (S-IGA) ......................................................... 42 
8.3. 
Other Efficacy Analyses ............................................................................................. 44 
8.4. 
Subgroup Analyses of Efficacy Variables .................................................................. 48 
9. 
SAFETY AND TOLERABILITY ANALYSIS ............................................................... 48 
9.1. 
Adverse Events ........................................................................................................... 49 
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 49 
9.1.2. Deaths and Serious Adverse Events ........................................................................... 49 
9.2. 
Local Tolerability Assessments .................................................................................. 50 
9.3. 
Clinical Laboratory Evaluations ................................................................................. 50 
9.4. 
Vital Signs ................................................................................................................... 50 
9.5. 
PHQ-8 and Modified PHQ-A ..................................................................................... 50 
9.6. 
C-SSRS ....................................................................................................................... 51 
9.7. 
Concomitant Medication ............................................................................................. 51 
9.8. 
Physical Examination.................................................................................................. 51 
10. 
OTHER PLANNED ANALYSIS ..................................................................................... 51 
10.1. Pharmacokinetic Analysis ........................................................................................... 51 
11. 
CHANGES FROM PLANNED ANALYSIS ................................................................... 52 
11.1. Version 2.0 .................................................................................................................. 52 
11.2. Version 3.0 .................................................................................................................. 52 
12. 
REFERENCES ................................................................................................................. 52 
14. 
TABLES, LISTINGS AND FIGURES ............................................................................ 54 
14.1. Planned Table Descriptions ........................................................................................ 54 
14.2. Planned Figure descriptions ........................................................................................ 61 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 7 of 63 
14.3. Planned Listing Descriptions ...................................................................................... 62 
 
 
 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 8 of 63 
LIST OF TABLES 
Table 1:  Schedule of Events ...................................................................................................... 17 
Table 2: 
Analysis Visit Windows (Study Visit) for Non-diary Assessments ........................... 26 
Table 3: 
Analysis Window for Calculation of Average Weekly SI-NRS and WI-NRS ........... 27 
Table 4: 
S-IGA and B-IGA ....................................................................................................... 36 
Table 5: 
Summary of Primary and Secondary Efficacy Analyses ............................................ 42 
Table 6: 
Summary of Analyses of Other Efficacy Endpoints ................................................... 44 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 9 of 63 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ATC 
Anatomical Therapeutic Chemical 
B-IGA  
Body Investigator Global Assessment of Disease 
BSA 
Body Surface Area 
CDISC 
Clinical Data Interchange Standards Consortium 
CDLQI 
Children's Dermatology Life Quality Index 
CFB 
Change from baseline 
CI 
Confidence Interval 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Novel Coronavirus Disease-19 
eCRF 
Case Report Form 
CSR 
Clinical Study Report 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
DLQI 
Dermatology Life Quality Index 
EMA 
European Medicines Agency 
EDC 
Electronic Data Capture  
FDA 
U.S. Food and Drug Administration 
ICH 
International Conference on Harmonisation 
IGA 
Investigator Global Assessment 
IP 
Investigational Product 
ITT 
Intent to Treat 
IWRS 
Interactive Web Response System 
LS-means 
Least squares means 
MCMC 
Markov-Chain Monte-Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
NRS 
Numeric Rating Score 
PASI 
Psoriasis Area and Severity Index 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 10 of 63 
Abbreviation 
Definition 
PASI-75 
Psoriasis Area and Severity Index-75; subjects who achieve a 75% 
reduction in PASI from baseline 
PHQ-8 
Patient Health Questionnaire  
PHQ-A 
Modified Patient Health Questionnaire for Adolescents 
PK 
Pharmacokinetics 
PMM 
Predictive Mean Matching 
PP 
Per Protocol  
PSD 
Psoriasis Symptoms Diary 
PSSI 
Psoriasis Scalp Severity Index 
PSSI-75 
Psoriasis Scalp Severity Index-75; subjects who achieve a 75% reduction 
in PSSI from baseline 
PT 
Prefered Term 
QD 
Once Daily ("quaque die") 
Q1 
First Quartile 
Q3 
Third Quartile 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation  
SE 
Standard Errors 
S-IGA 
Scalp Investigator Global Assessment of Disease  
SI-NRS 
Scalp Itch - Numeric Rating Scale 
SOC 
System Organ Class 
TEAE 
Treatment-emergent Adverse Event 
TESAE 
Treatment-emergent Serious Adverse Event 
TLFs 
Tables, Listings, and Figures 
WI-NRS 
Worst Itch - Numeric Rating Scale 
WHO 
World Health Organization 
 
 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 11 of 63 
1. 
OVERVIEW 
This statistical analysis plan (SAP) describes the planned analysis and reporting for Arcutis 
Biotherapeutics, Inc. protocol number ARQ-154-309 (A Phase 3, 8-Week, Parallel Group, 
Double Blind, Vehicle-Controlled Study of the Safety and Efficacy of ARQ-154 Foam 0.3% 
Administered QD in Subjects with Scalp and Body Psoriasis (ARRECTOR)), dated 29-Jul-2022, 
Amendment 3. Version 1 of the ARQ-154-309 SAP was based on protocol amendment 2 dated 
12-May-2022 and was approved on 31-May-2022.  Protocol Amendment 3, dated 29Jul2022, 
and SAP Version 2.0 (11-Aug-2022) were created to update the multiple testing strategy for 
secondary endpoints to reflect the change in the PSD secondary endpoints and to move SI-NRS 
change from baseline at Day 1 endpoint from Family 1 to Family 3 in the multiple testing 
strategy. The ARQ-154-309 database was locked on 09-Sep-2022 and unblinded on 12-Sep-
2022.  On 9-Sep-2022, FDA provided the following advice in preliminary feedback prior to a 
pre-NDA meeting for a similar program held on 14-Sep-2022. 
For the primary estimand, you proposed a treatment policy strategy to handle all 
intercurrent events, including treatment discontinuation due to adverse event or lack of 
efficacy. For intercurrent events of treatment discontinuation due to adverse events or lack 
of efficacy, we recommend a composite strategy policy where subjects will be defined as 
non-responders, as we consider this to be the appropriate approach for handling such 
events. Your proposal to handle intercurrent events of treatment discontinuation using the 
treatment policy strategy can be used as part of a supportive estimand. 
The purpose of this version of the SAP is to document the change to the primary estimand and 
related multiple imputation strategies. The revised estimand will be the focus of the Clinical 
Study Report and NDA.  Key results based on the original estimand defined in SAP versions 1 
and 2 will be provided as supplemental information for the primary and secondary endpoints 
covered by the multiple testing strategy. 
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 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association3 and the Royal Statistical Society1, 
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. 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 12 of 63 
The statistical plan described hereafter is an a priori plan. It will be submitted to file prior to any 
unblinded inferential or descriptive analysis of data pertaining to Arcutis Biotherapeutics, Inc.’s 
study ARQ-154-309.  
ARQ-154 foam 0.3% will be described as “roflumilast foam 0.3%” throughout this document 
and the tables, listings, and figures (TLFs). 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. Primary Objective 
The primary objective of this study is to assess the safety and efficacy of roflumilast foam 0.3% 
administered once daily (QD) vs. vehicle foam for 8 weeks in adolescent and adult subjects with 
scalp and body psoriasis. 
2.2. 
Study Endpoints 
2.2.1. Safety Endpoints 
The safety endpoints of this study include the following: 
• Adverse events (AEs) 
• Local tolerability assessments 
• Clinical laboratory parameters 
• Vital signs/weight 
• Patient Health Questionnaire depression scale (PHQ-8) and Modified PHQ-Adolescents 
(PHQ-A) 
• Columbia-Suicide Severity Rating Scale (C-SSRS) 
• Physical examinations 
2.2.2. Efficacy Endpoints 
2.2.2.1. 
Co-Primary Efficacy Endpoints 
The co-primary efficacy endpoints of this study are: 
• Scalp Investigator Global Assessment (S-IGA) Success at Week 8, defined as 
achievement of S-IGA score of “Clear” or “Almost Clear” plus at least 2-grade 
improvement from baseline. 
• Body Investigator Global Assessment (B-IGA) Success at Week 8, defined as 
achievement of B-IGA score of “Clear” or “Almost Clear” plus at least 2-grade 
improvement from baseline. 
2.2.2.2. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints of this study include the following:  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
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• For the subjects with Baseline Scalp Itch – Numeric Rating Scale (SI-NRS) score ≥ 4, 
achievement of at least 4-point improvement (reduction) from baseline in SI-NRS at 
Week 8 (SI-NRS Success at Week 8) 
• SI-NRS Success at Week 4  
• SI-NRS Success at Week 2  
• SI-NRS Change from baseline (CFB) at Week 1 
• SI-NRS CFB at 72 hours 
• For the subjects with Baseline Worst Itch – Numeric Rating Scale (WI-NRS) score ≥ 4, 
achievement of at least a 4-point improvement (reduction) from baseline in WI-NRS at 
Week 8 (“WI-NRS Success at Week 8”) 
• Psoriasis Area and Severity Index (PASI)-75 at Week 8 
• CFB in Psoriasis Symptoms Diary (PSD) Items related to Itching, Pain, and Scaling 
(Questions 1, 9, and 11) aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• Psoriasis Scalp Severity Index (PSSI)-75 at Week 8 
• S-IGA score of “Clear” at Week 8 
• S-IGA Success at Week 4 
• CFB in PASI at Week 2 
• S-IGA Success at Week 2 
• PSD Total Score = 0 at Week 8 
• SI-NRS CFB at Day 1 
2.2.2.3. 
Other Efficacy Endpoints 
The efficacy endpoints listed below are not explicitly defined in the protocol but are based on 
other efficacy assessments collected: 
S-IGA 
• S-IGA score of “Clear” at Weeks 2 and 4 
• Change from baseline in S-IGA at Weeks 2, 4, and 8 
B-IGA 
• B-IGA success at Weeks 2 and 4 
• B-IGA score of “Clear” at Weeks 2, 4, and 8 
• B-IGA score of “Clear” or “Almost Clear” at Weeks 2, 4, and 8 
• Change from baseline in B-IGA at Weeks 2, 4, and 8 
SI-NRS 
• SI-NRS Success at Weeks 1, 3, 5, 6, and 7  


 
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• Change and percent change from baseline in SI-NRS at Weeks 2, 3, 4, 5, 6, 7, and 8 
WI-NRS 
• WI-NRS Success at Weeks 1, 3, 5, 6, and 7.  
• Change and percent change from baseline in WI-NRS at Weeks 1, 2, 3, 4, 5, 6, 7, and 8 
PASI 
• PASI-75 at Weeks 2 and 4 
• PASI-50, PASI-90, and PASI-100 at Weeks 2, 4, and 8 
• Change from baseline in PASI at Weeks 4 and 8 
• Percent change from baseline in PASI at Weeks 2, 4, and 8 
PSD 
• Change and percent change from baseline in PSD total score at Weeks 2, 4, and 8 
• Change and percent change from baseline in PSD individual item scores at Week 2, 4, 
and 8  
• Change and percent change from baseline in an aggregate score for a subset of 3 PSD 
individual items at Weeks 2 and 4.  Items addressing Itching, Pain and Scaling (Questions 
1, 9, and 11) will be aggregated into a single score and results of the aggregate (0-30) 
score will be analyzed. 
• Percent change from baseline in PSD Items related to Itching, Pain, and Scaling 
(Questions 1, 9, and 11) aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Weeks 2 and 4 
• PSD Item related to Itching (Question 1) = 0 at Weeks 2 and 4 
• PSD Item related to Pain (Question 9) = 0 at Weeks 2 and 4 
• Achievement of PSD Total Score = 0 at Weeks 2 and 4 
PSSI 
• PSSI-75 at Weeks 2 and 4 
• PSSI-50, PSSI-90, and PSSI-100 at Weeks 2, 4, and 8 
• Change and percent change from baseline in PSSI at Weeks 2, 4, and 8 
 
Scalpdex 
• Change and percent change from baseline in Scalpdex total score as well as the emotions, 
symptoms, and functioning scales at Weeks 2, 4, and 8 
% BSA Affected by Psoriasis 
• Change and percent change from baseline in total body % BSA affected by psoriasis at 
Weeks 2, 4, and 8 
Extent of Scalp Involvement 
• Change and percent change from baseline in percent of scalp affected by psoriasis at 
Weeks 2, 4, and 8 


 
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DLQI/CDLQI 
• Change and percent change from baseline in Dermatology Life Quality Index (DLQI)/ 
Children’s DLQI (CDLQI) total scores at Weeks 2, 4, and 8 
3. 
OVERALL STUDY DESIGN AND PLAN 
3.1. 
Overall Design 
This is a phase 3, parallel group, double blind, vehicle-controlled study in which roflumilast 
foam 0.3% or vehicle foam is applied QD x 8 weeks to adolescent and adult subjects with a 
minimum S-IGA of “Moderate” (3) and a minimum B-IGA of “Mild” (2). 
Approximately 420 subjects will be enrolled.  Subjects will be randomized in a 2:1 ratio to 
roflumilast foam 0.3% QD or matching vehicle foam QD, which will be applied to all areas of 
scalp and body psoriasis (including the face, scalp, trunk, and intertriginous/genital regions; 
palms and soles may be treated but will not be counted towards any measurements of efficacy). 
Screening will be for up to 4 weeks followed by an 8-week Treatment Phase. The anticipated 
maximum duration of subject participation is approximately 12 weeks. 
Subjects will have to apply the study drug once a day in the evening, except for Baseline/Day 1 
and Week 2 (Visit 3) when the study drug is applied at the study site. Participants have to record 
the date and time each dose has been applied with details including missed doses and any 
additional comments.  
3.2. 
Sample Size and Power 
A sample size of up to approximately 420 subjects is planned for the study. Approximately 
280 subjects will receive roflumilast foam 0.3% QD; approximately 140 subjects will receive 
vehicle foam QD.  
This sample size provides more than 99% power to detect an overall 35% difference between 
treatment groups on S-IGA success at Week 8 (11% and 46% success rates in roflumilast and 
vehicle arms corresponding to an odds ratio=6.9).  This sample size also provides more than 99% 
power to detect an overall 25% difference between treatment groups on B-IGA success at Week 
8 (7% and 32% success rates in roflumilast and vehicle arms corresponding to an odds ratio of 
6.4).  Testing will be performed at α=0.025 using a 2-sided stratified (B-IGA at randomization, 
S-IGA at randomization and study site) Cochran-Mantel-Haenszel (CMH) test. The results from 
a recent phase 2 study (ARQ‑154-204) of roflumilast foam 0.3% compared to vehicle treatment 
were used as the basis of the power calculations.   
The number of subjects to be enrolled will also provide at least 90% power for most of the 
secondary endpoint analyses. The study is highly powered in order to provide sufficient numbers 
of subjects on roflumilast foam treatment for a safety database, and to provide robust results due 
to the single pivotal trial nature of this study. 
3.3. 
Study Population 
Study population consists of male and female adolescents (12-17 years old) and adults 
(≥18 years old). Subjects should have a minimum S-IGA of at least “Moderate” (3) and B-IGA 


 
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of at least “Mild” (2) at baseline.  
3.4. 
Treatments Administered 
Subjects who meet the eligibility criteria will be randomized to 1 of the 2 following treatment 
groups in a 2:1 ratio (active: vehicle): 
• Roflumilast foam 0.3% QD 
• Matching vehicle foam QD 
3.5. 
Method of Assigning Subjects to Treatment Groups 
Subjects are randomized and assigned to active treatment or vehicle at the Baseline/Day 1 visit. 
Assignment of roflumilast foam 0.3% QD or vehicle foam QD is made at a 2:1 ratio according to 
a computer-generated randomization list. Randomization is stratified by study site, baseline 
S-IGA (S-IGA = 3 vs. S-IGA = 4), and baseline B-IGA (B-IGA = 2 vs. B-IGA ≥ 3). 
3.6. 
Blinding and Unblinding 
This is a double-blinded study, therefore neither the subjects nor the Investigator, clinical 
personnel, or Sponsor are aware of which treatment an individual subject has received. 
Emergency unblinding will be done using the study internet-based randomization system 
(interactive web-response system; IWRS) system in consultation with the medical monitor. Refer 
to the current IWRS Plan for details on unblinding.   
3.7. 
Schedule of Events 
A detailed schedule of events for the study is provided in Table 1. 


 
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Table 1:  
Schedule of Events 
Study Procedure 
Screening 
Baseline 
Day 1 
Week 2 
Day 15 
Week 4 
Day 29 
Week 8a 
Day 57 
Visit 
1 
2 
3 
4 
5 
Visit Window 
-4 Weeks 
 
± 3 Days 
± 5 Days 
± 5 Days 
Informed consent/assent 
X 
 
 
 
 
Medical/surgical history, demography 
X 
 
 
 
 
Physical examinationb 
X 
X 
 
 
X 
Fitzpatrick Skin Type 
X 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
Randomization 
 
X 
 
 
 
Hematology, Chemistry, and Urinalysisc 
X 
X 
 
X 
X 
Vital signs, weight, heightd 
X 
X 
X 
X 
X 
S-IGAe, B-IGAe, PSSIe, BSAf, Extent of 
Scalp Involvementg, PASI 
X 
X 
X 
X 
X 
DLQI/CDLQIh, Scalpdexh, PSDh  
X 
X 
X 
X 
X 
Daily SI-NRS and WI-NRSi at home 
(non-clinic) 
Day -7 through Day 57 
Application Site Reaction Assessment/ 
Local Tolerabilityj  
 
X 
X 
X 
X 
C-SSRS, PHQ-8/PHQ-Ak 
X 
X 
 
X 
X 
Medical Photographyl 
 
X 
X 
X 
X 
Follicle Stimulating Hormone (FSH)m 
X 
 
 
 
 
Serum pregnancy testm 
X 
 
 
 
 
Urine pregnancy testn 
 
X 
 
X 
X 
PK samplingo 
 
 
 
X 
X 
IP application and subject/family trainingp 
 
X 
X 
X 
 
Dispense investigational product kitq 
 
X 
X 
X 
 
Dispense / review dosing diary 
 
X 
X 
X 
X 
Weigh investigational productr 
 
X 
X 
X 
X 
Compliance calculations 
 
 
X 
X 
X 
Adverse event assessmentt 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
 
 
Footnotes from table above: 


 
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a. 
Subjects that terminate early should return to the study site for the Week 8 assessments. 
b. 
Limited physical examination: skin (including assessment of Fitzpatrick Skin Type at Screening only), lungs, 
and heart only. 
c. 
For subjects <18 years of age, if the Baseline/Day 1 visit occurs within 3 weeks of Screening, the Screening lab 
results may be utilized. 
d. 
Height will be collected at Screening and Week 8. Weight will be collected at all study visits. Subjects should 
void prior to weight being taken and remove any objects of significant weight (i.e., jackets, outerwear, shoes, 
cell phones, wallet, key chains, etc.). A 5% unintentional weight loss from Baseline should be reported to the 
medical monitor. 
e. 
S-IGA will be a 5-point scale ranging from clear (0) to severe (4) and is evaluated for the scalp only. B-IGA 
will use the same scale as S-IGA but will evaluate the entire body (except the scalp, palms, and soles).  PSSI is 
scored on a 0-72 scale and evaluates the scalp only.  PASI assessment should exclude palms and soles.  S-IGA 
and B-IGA should be completed prior to other Investigator assessments and every effort should be made 
for the same evaluator to complete at each study visit. 
f. 
Total BSA affected by scalp and body psoriasis 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. Scalp will be 
included in total BSA measurement, but palms and soles will be excluded. The total scalp (ie, 100% of the total 
scalp surface area) can be considered to be approximately 4% BSA. 
g. 
Extent of scalp involvement will be the extent of psoriasis involved, expressed as a percentage of total scalp. 
h. 
The DLQI will be completed by subjects ≥17 years of age. The CDLQI will be completed for subjects 
12 to 16 years old, inclusive. Scalpdex will be completed by all subjects. PSD will be completed by subjects 
≥ 18 years of age. 
i. 
Subjects/parents/caregivers will complete the SI-NRS and WI-NRS daily at home starting 7 days prior to the 
Baseline/Day 1 visit to Day 57 (Week 8) visit. Daily SI-NRS and WI-NRS will be completed in the evening 
prior to IP application (except at Baseline and Week 2 when IP is applied at the clinic). The SI-NRS should be 
completed first and then WI-NRS. 
j. 
Local tolerability assessments include both investigator and subject assessments.  The Investigator assessment 
of skin irritation (Berger and Bowman skin irritation score) is to be recorded prior to IP application.  
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 
psoriasis. The subject’s “0-3” burning/stinging assessment is to be recorded 10-15 minutes post IP application 
for the subject’s “0-3” burning/stinging assessment.  At Week 8, subjects will provide a recall assessment of 
burning/stinging experienced post IP application on the day prior to the clinic visit. 
k. 
All subjects will complete the C-SSRS. Adults will complete the PHQ-8. Adolescents (ages 12 to 17 inclusive) 
will complete the PHQ-A (PHQ-9 modified). Refer screen failures due to score ≥10 to a mental health 
professional. For Scores 10-14 at all visits, refer subject promptly to a mental health professional. For scores 
≥15 at all visits, refer subject promptly to a mental health professional and consider interruption of IP. 
l. 
Medical photography will be obtained for target lesions by all sites. All efforts will be made to de-identify the 
subjects. 
m. 
A serum pregnancy test will be administered to all females of child-bearing potential at the Screening visit only. 
Follicle Stimulating Hormone (FSH) will be performed at Screening (if indicated) to confirm post-menopausal 
status. 
n. 
A urine pregnancy test will be performed at the Baseline, and Weeks 4 and 8 to all females of child-bearing 
potential. A negative result is required for continued participation in the study, and results must be available at 
each visit prior to dispensing of IP. 
o. 
PK samples (trough) will be collected predose on Day 29 (Week 4) and Day 57 (Week 8). Ensure 
investigational product is not applied in the area where PK will be drawn. 
p. 
Subjects/parents/caregivers to apply assigned IP in the study site at every designated visit.  
q. 
Kits will be dispensed based on % BSA. See IP Handling Plan for details. 
r. 
Each IP canister in the Kit should be weighed and recorded at every visit. See IP Handling Plan for details. 
s. 
Compliance calculation is described Section 6.1.7 and in the IP Handling Plan. 


 
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Footnote from table above: 
t. 
All AEs should be collected starting after the first application of the IP through the end of the study. All SAEs 
should be collected starting after the signing of the informed consent through 30 days after the last day of the IP 
application or the end of the study (whichever is later). Any AEs (whether serious or non-serious) and clinically 
significant abnormal laboratory test value(s) will be evaluated by the Investigator and treated and/or followed 
up to 30 days after end of treatment or until symptoms or value(s) return to subject’s Baseline, or acceptable 
level, as judged by the PI. 
4. 
STATISTICAL ANALYSIS AND REPORTING 
4.1. 
Introduction 
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations, will be performed primarily using SAS (release 9.4 or higher). If the 
use of other software is warranted for analyses conducted by Premier Research, 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 
nonmissing values, mean, standard deviation (SD), median, minimum, maximum, first quartile 
(Q1), and third quartile (Q3).  
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 the treatment group, unless otherwise specified.  
Unless otherwise indicated, all statistical tests will be conducted at the familywise α=0.025 
significance level using 2-tailed tests, and P values will be reported. Corresponding 95% and 
97.5% confidence intervals will be presented for statistical tests. Details for splitting the 
familywise α to control for multiple comparisons will be discussed in Section 6.1.3. 
All data collected in the electronic case report form (eCRF) will be provided in subject listings. 
4.2. 
Interim Analysis and Data Monitoring 
No interim analyses are planned. 
5. 
ANALYSIS POPULATIONS 
The following analysis populations are planned for this study:  
• Safety Population (SAF): The Safety population will include all subjects who are 
randomized and received at least 1 confirmed dose of investigational product (IP). This 
population will be used for all safety analyses. 
• Intent-To-Treat Population (ITT): The ITT population will include all randomized 
subjects. This population will be the primary analysis population for the analysis of 
efficacy endpoints, along with subject disposition.  


 
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• Per Protocol (PP) Population: The PP population will include the subjects in the ITT 
population who were at least 80% compliant with study drug application, have an S-IGA 
and B-IGA assessment at Week 8, and showed no important deviations from the study 
protocol that would affect the interpretation of efficacy. “Important deviations” will result 
from a blinded review at the end of the study and the team will determine the important 
deviations that can impact on efficacy. This population will be used for a supplemental 
analysis for primary efficacy endpoints. 
• Modified Intent-to-Treat Population (mITT): The mITT population includes all 
randomized subjects with the exception of subjects who missed the Week 8 S-IGA or B-
IGA assessment specifically due to COVID-19 disruption. This population will be used 
for sensitivity of the primary endpoints. 
• Scalp Pruritus ITT Population (SPRU4-ITT): The SPRU4-ITT population is a subset 
of the ITT population and includes subjects with average weekly SI-NRS score ≥ 4 at 
baseline. This population will be used for the analysis of achievement of at least 4-point 
reduction in average weekly SI-NRS score as compared to baseline. 
• Pruritus ITT Population (PRU4-ITT): The PRU4-ITT population is a subset of the ITT 
population and includes subjects with average weekly WI-NRS score ≥ 4 at baseline. 
This population will be used for the analysis of achievement of at least 4-point reduction 
in average weekly WI-NRS score as compared to baseline. 
• Pharmacokinetic Population (PK): The PK population will include all subjects who 
received at least one confirmed dose of investigational product (IP) and provided at least 
one PK sample. This population will be used for summary of PK concentration results for 
subjects who applied roflumilast foam 0.3% during this study.   
6. 
GENERAL ISSUES FOR STATISTICAL ANALYSIS 
6.1. 
Statistical Definitions and Algorithms 
6.1.1. Baseline 
In general, for assessments where time was recorded, the last observation recorded at or before 
the time of first application of study drug will be used as the baseline observation for all 
calculations of change from baseline. If the date and time of the assessment is equal to the date 
and time of the start of the first application of study drug, it will be assumed that the assessment 
was completed before study drug application and the value will be used as baseline.  For 
assessments where time was not recorded (excluding SI-NRS and WI-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. If the last non-missing assessment is 
performed on the same date as the first study treatment administration and time is not available, 
it is assumed that the assessment took place prior to IP application, per study site training, and 
the assessment will be considered as baseline, except adverse events (AEs) and medications 
starting on the first study treatment dose administration date which will be considered 
postbaseline.  
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scores reported during the last 7 days prior to treatment if at least 4 of 7 evaluable daily 
questionnaires scores are available. For daily SI-NRS and daily WI-NRS baseline is defined as 
the last non-missing assessment prior to the first study treatment.  
For subject tolerability assessments, baseline is derived as the last non-missing measurement 
taken on the day of first application of study drug. 
6.1.2. Adjustments for Covariates 
Covariates for this study include the pooled site group (see Section 6.1.6), baseline S-IGA 
randomization strata (S-IGA = 3 vs. S-IGA =4) and baseline B-IGA randomization strata (B-
IGA = 2 vs. B-IGA ≥ 3).  
6.1.3. Multiple Comparisons 
Upon demonstration of concurrent statistical significance for S-IGA Success at Week 8 at the 
2.5% level, and statistical significance of B-IGA Success at Week 8 at the 2.5% level, the testing 
scheme described below will be used to test these secondary endpoints. This testing scheme will 
control the overall type 1 error at the 0.025 level. 
The overall α level of 0.025 will be split to test 3 families of secondary endpoints, and the 
Fallback Method will be applied across the families. 
Family 1 (α=0.01 or 0.015): 
• SI-NRS Success at Week 8  
• SI-NRS Success at Week 4 
• SI-NRS Success at Week 2 
• SI-NRS change from baseline (CFB) at Week 1 
• SI-NRS CFB at 72 hours 
 
Family 2 (α=0.005): 
• WI-NRS Success at Week 8 
• PASI-75 at Week 8 
• CFB in PSD Items related to Itching, Pain, and Scaling (Questions 1, 9, and 11) 
aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• PSSI-75 at Week 8  
 
Family 3 (α=0.01 or 0.02 or 0.025): 
• S-IGA score of “Clear” at Week 8 
• S-IGA Success at Week 4 


 
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• CFB in PASI at Week 2 
• S-IGA Success at Week 2 
• PSD Total Score = 0 at Week 8  
• SI-NRS CFB at Day 1 
 
The Fallback Method will be used to pass unused alpha across the Families.  The Families will 
be tested in this order:  Family 2, Family 1, Family 3.   Testing will be sequential within Family 
2 and Family 1, with the order of testing of each endpoint within each family as listed above.   
Testing within Family 3 will be implemented with Holm’s procedure.   
To start, Family 2 will be tested, sequentially within Family 2, each endpoint at the α=0.005 
level.  Should the testing succeed through all seven endpoints in Family 2, the α=0.005 will 
remain unused, and will be passed to Family 1.  
The testing of the five SI-NRS endpoints in Family 1 will be sequential, either at the α=0.01 
level (assumes Family 2 had an unsuccessful test), or the α=0.015 level (assumes all endpoints in 
Family 2 were successful at the α=0.005 level). 
Family 3 contains six endpoints.  Family 3 has initially been allocated α=0.01.  This creates three 
possible testing alpha levels for the Family 3 endpoints:   
• If all tests in Family 1 (α=0.01) and Family 2 (α=0.005) are successful, then 
α=0.005+0.01=0.015 is unused, and the α=0.015 will be carried to Family 3, allowing 
Family 3 endpoints to be tested at the full 0.025 level. 
• If the α=0.005 in Family 2 is used, but the subsequent α=0.01 allocated to Family 1 is not 
used, then Family 3 endpoints will be tested at the α=0.01+0.01=0.02 level. 
• If the α=0.01 in Family 1 is used, and the α=0.005 in Family 2 is also used, then Family 3 
endpoints will be tested at α=0.01. 
6.1.4. Handling of Dropouts or Missing Data  
6.1.4.1. 
Imputation of Missing Data 
6.1.4.1.1 
Imputation for the primary estimand  
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 subjects who discontinue due 
to lack of efficacy or adverse event, the last dose day will be assigned to an analysis window 
similarly as described in Section 6.1.5. To comply with the definition of the primary estimand 
(Section 8.1.1), efficacy data assigned to a pre-specified analysis visit will be removed from the 
source data used for the multiple imputation process for visits on or after the assigned analysis 
visit of the last dose day for these subjects. Similarly, SI-NRS and WI-NRS weekly averages will 
be removed from the source data used for multiple imputation for weeks on or after the assigned 
analysis week of the last dose day for these subjects . This procedure will ensure that the data 
collected after intercurrent events are not used in the imputation process.  


 
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For the co-primary and secondary efficacy endpoints (i.e., S-IGA, B-IGA, weekly average SI-
NRS, weekly average WI-NRS, total PSD score = 0, aggregated PSD score of itching, pain and 
scaling, PSD score of scaling item of 0, PSD score of the itching item of 0, PSD score of pain 
item=0,   PASI, and PSSI), the 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 and Week 8 visits, but missing values for the Week 2 or 4 visits, 
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 66447809. All the endpoints will be considered as 
continuous for this step. To avoid values that could not be observed in practice for 
S-IGA, B-IGA, total PSD score, and PSSI, imputed values will be constrained to be 
integers in the range of the observed endpoint. Since SI-NRS and WI-NRS scores will be 
calculated as average weekly scores and PASI is a derived score that can have 
non-integer results (see Section 6.1.7 for more information), this restriction will not apply 
for those endpoints. Total of 10 imputations are done in the MCMC step. 
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, the outcome at 
previous visits, pooled site, and treatment group using a seed of 90066927. This process 
will be repeated 15 times, resulting in a total of 150 complete analysis datasets. The seed 
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 categorical 
endpoints will be analyzed using the CMH analysis for each of the complete analysis data 
sets stratified by pooled site group, baseline S-IGA category, and baseline B-IGA 
category. The results will be combined into one multiple imputation inference (odds ratio, 
associated CI, and P value) using PROC MIANALYZE as illustrated4. The continuous 
endpoints will be analyzed using descriptive summaries, and an ANCOVA for each of 
the complete analyses data sets with terms for the baseline outcome, pooled site group, 
baseline S-IGA category, and baseline B-IGA category as covariates. The descriptive 
summaries will use the averaged imputed outcomes across all datasets for each subject, 
and the ANCOVA results will be combined into one multiple imputation inference 
(LS means, standard errors [SEs], 95% CIs, 97.5% CIs, and P values) using PROC 
MIANALYZE as illustrated4. 
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 


 
Statistical Analysis Plan  
 
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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 S-IGA and B-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=66447809 nimpute=10 round=1 out=example_1; 
  mcmc impute=monotone; 
  var <baseline score> ………… <visit8 score>; 
run; 
Step 2: 
proc mi data=example_1 seed=90066927 nimpute=15  out=example_2; 
  by <MCMC imputation>; 
  class <treatment> <pooled site>; 
  monotone regpmm(<baseline score> ………… <visit8 score>); 
  var <treatment> <pooled site> <baseline score> ………… <visit8 score>; 
run; 
 
Step 3:  
a) For categorical outcomes, this step involves running a CMH test stratified by pooled site 
group, baseline S-IGA randomization strata, and baseline B-IGA randomization strata on 
each completed dataset and combining the results using PROC MIANALYZE. 
proc freq data=example noprint; 
  by <imputationnumber> <visit> ; 
  tables <pooled site group> * <BL S-IGA randomization strata> * <BL B-IGA 
randomization strata> * <treatment>  
         * <outcome> / cmh commonriskdiff(cl=MH) alpha=0.025; 
  output out=example_stat cmh; 
run; 
In order to apply PROC MIANALYZE for the categorical outcomes, normalizing 
transformations have to be applied to odds ratio. P values are obtained using Wilson 
Hilferty transformation as illustrated by Ratitch et.al.4. 
b) For continuous outcomes, this step involves running an ANCOVA with terms for the 
baseline outcome, pooled site group, baseline S-IGA category, and baseline B-IGA 
category as covariates for each of the completed dataset and combining the results using 
PROC MIANALYZE 
proc mixed data=example; 
  by <imputationnumber> <visit> ; 
  class <pooled site group> <BL S-IGA randomization strata > <BL B-IGA 
randomization strata > <treatment>; 
  model <outcome> = <pooled site group> <BL S-IGA randomization strata> <BL 
B-IGA randomization strata>  
        <treatment> <base> / alpha=0.025; 


 
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  lsmeans <treatment> / alpha=0.025 pdiff cl; 
  ods output lsmeans=lsmeans 
             diffs=diffs; 
run; 
 
*Combines the LS means across the MI datasets; 
proc sort data=lsmeans; 
  by <treatment> <imputationnumber>; 
run: 
 
proc mianalyze data=lsmeans; 
  by <treatment>; 
  modeleffects estimate; 
  stderr stderr; 
run; 
 
*Combines the LS mean differences across the MI datasets; 
proc sort data=diffs; 
  by <treatment> <imputationnumber>; 
run: 
 
proc mianalyze data=diffs; 
  by <treatment>; 
  modeleffects estimate; 
  stderr stderr; 
run; 
 
6.1.4.1.2 
Imputation for supplemental estimand 
The originally pre-specified primary analysis estimand will remain unchanged, but will be re-
labeled as a supplemental estimand and will handle all intercurrent events using a “Treatment 
Policy Strategy” (Section 8.1.1).  Imputation for the supplemental estimand will be similar to the 
process described above for the primary estimand; however, subjects who discontinue due to 
lack of efficacy or adverse event will be treated the same as those who did not discontinue for 
one of those reasons.  All observed data for these subjects will be included in the imputation 
process subject to the analysis visit window strategy described in Section 6.1.5.  
 
6.1.4.2. 
Tipping Point Analysis 
As a sensitivity analysis to the multiple imputation analysis as described in Section 6.1.4.1 for 
the S-IGA and B-IGA co-primary endpoints, a tipping point analysis will be performed in order 
to determine the inflection point at which the inference under the MNAR assumption changes 
substantially. This will be used to check the robustness of the imputation. 
The sensitivity analysis will be performed by using a specified sequence of shift parameters, 
which will adjust the imputed values for observations in both treatment groups. The range of 
shift parameters to be included in this analysis will be 0 to 2 by 0.5 for the active group and -2 to 
0 by 0.5 for the vehicle group. Once the likely point of the shift is determined, the analysis may 
be rerun using a more focused range around the suspected tipping point. Thus, the value at which 
the results of the analysis are shifted from significant (i.e., α ≤ 0.025) to nonsignificant 


 
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(i.e., α > 0.025) will be determined. 
Step 1 and 3 of the analysis will be the same as for the multiple imputation analysis as described 
in Section 6.1.4.1.1 However, Step 2 of the analysis is where the shift parameters will be applied.  
Pseudo-code for Step 2 is as follows: 
proc mi data=example_1 seed=90066927 nimpute=15  out=example_2; 
  by <MCMC imputation>; 
  class <treatment> <pooled site group.; 
  monotone regpmm(<baseline score> ………… <visit8 score>); 
  var <treatment> <pooled site group> <baseline score> ………… <visit8 score>; 
  mnar adjust(<visit2 score> / shift=YY adjustobs=(treatment=‘Roflumilast 
Foam 0.3%’));  
  mnar adjust(<visit4 score> / shift=YY adjustobs=(treatment=‘Roflumilast 
Foam 0.3%’)); 
  mnar adjust(<visit8 score> / shift=YY adjustobs=(treatment=‘Roflumilast 
Foam 0.3%’)); 
  mnar adjust(<visit2 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’));  
  mnar adjust(<visit4 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’)); 
  mnar adjust(<visit8 score> / shift=ZZ adjustobs=(treatment=‘Vehicle 
Foam’)); 
run; 
YY and ZZ will encompass all combinations of the range of shift parameters as 
pre-specified above. 
Imputed values for subjects who discontinue due to lack of efficacy or adverse event will be 
handled as described in Section 6.1.7 to ensure that these subjects are analyzed as non-responders 
at all visits on or after discontinuation of treatment. 
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 2. Visits falling outside of these windows will not 
be windowed (e.g., an unscheduled visit before first application of study drug). The windows 
follow the Schedule of Events in Table 1. Unscheduled/repeated measurements will be listed.  
Table 2: 
Analysis Visit Windows (Study Visit) for Non-diary Assessments 
Visit  
Name 
Visit  
Number  
Target Start  
Day 
Lower  
Limit 
Upper  
Limit 
Week 2 
3 
15 
2 
22 
Week 4 
4 
29 
23 
42 


 
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Visit  
Name 
Visit  
Number  
Target Start  
Day 
Lower  
Limit 
Upper  
Limit 
Week 8 
5 
57 
43 
--- 
6.1.5.2. 
Diary Assessments (WI-NRS, SI-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 3.  
Table 3: 
Analysis Window for Calculation of Average Weekly SI-NRS and WI-NRS 
Study Days for Calculation of average 
weekly WI-NRS 
Week (Derived) 
(-7, -1) or (-6, 1)* 
Baseline 
(2, 7) 
Week 1 
(8, 14) 
Week 2 
(15, 21) 
Week 3 
(22, 28) 
Week 4 
(29, 35) 
Week 5 
(36, 42) 
Week 6 
(43, 49) 
Week 7 
(50, 56)  
Week 8 
* If the Day 1 score is collected after the first treatment application use data from days  (-7, -1), otherwise use data 
from days (-6, 1). If Day 1 time of assessment is unknown, assume that the assessment was obtained prior to the 
first treatment application as prescribed by the protocol. If a subject does not have assessment performed on Day 
1, then (-7, -1) window will be used in determining the average scores. 
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 
Efficacy variable derivations described in this section will be performed with one exception. The 
exception is that subjects who discontinued early from study due to an AE or lack of efficacy 
will be considered as not having response (for MI and non-responder imputation analyses) and 
will be excluded from observed case analyses for all pre-specified analysis visits (refer to Section 


 
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6.1.5)  on or after the associated analysis visit of the subject’s last dose day ). More specifically, 
for MI and non-responder imputation analyses, these subjects will be counted as non-responders 
for categorical variables and set to baseline for continuous variables for all visits on or after the 
associated analysis visit of the subject’s last dose day. 
• Study day is calculated as:  
o observation date – first dose date + 1, if record is collected on or after first dose 
date  
o observation date – first dose date, if record is collected prior to first dose date. 
• S-IGA Success = S-IGA of “Clear” or “Almost Clear” plus at least 2-grade improvement 
from baseline.  
• B-IGA Success = B-IGA of “Clear” or “Almost Clear” plus at least 2-grade improvement 
from baseline.  
• Average Weekly SI-NRS Score = SI-NRS scores will be assigned to a particular study 
week based on the study week window, as shown in Section 6.1.5.2. Average weekly 
baseline SI-NRS is derived as the average of all non-missing scores reported during the 
last 7 days prior to treatment if at least 4 of 7 evaluable daily SI-NRS questionnaires are 
available. Daily baseline SI-NRS is defined as the last non-missing assessment prior to 
the first study treatment. 
If 2 or more observations are present for a single day, the most severe itch score will be 
used as a single daily value before calculating the average weekly score. The average of 
the reported (non-missing) SI-NRS scores assigned to each study week will be calculated. 
If at least 4 SI-NRS scores are present in this time period, the average weekly SI-NRS 
score will be calculated; otherwise, the average weekly score will be missing for that 
week. The derived average score will be rounded to 1 digit. Missing average weekly 
scores will be imputed as described in Section 6.1.4.1.  
• SI-NRS Success = achievement of at least 4-point reduction in average weekly SI-NRS 
score compared to baseline, calculated only for the subjects with SI-NRS ≥ 4 at baseline.   
Day 1 and 72-hour SI-NRS = the Day 1 and 72-hour endpoints are meant to measure the 
response to the first and first 3 treatment applications, respectively.  The relevant 
assessments are the ones reported prior to IP application on study days 2 and 4 where 
study day is calculated as described earlier in this section.  
 
• 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, the most severe itch score will be 
used for that day. The average of the reported (nonmissing) WI-NRS pruritus scores 
assigned to each study week will be calculated. If at least 4 WI-NRS pruritus scores are 
present in this time period, the average weekly WI-NRS pruritus score will be calculated 
similar to SI-NRS; otherwise, the average weekly score will be missing for that week. 
Missing average weekly scores will be imputed as described in Section 6.1.4.1. 


 
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• WI-NRS Success = achievement of at least 4-point reduction in average weekly WI-NRS 
score compared to baseline, calculated only for the subjects with WI-NRS ≥ 4 at baseline.   
• PASI = (0.1×[Eh + Th + Sh]×Ah) + (0.2×[Ea + Ta + Sa]×Aa) + (0.3×[Et + Tt + St]×At) + 
(0.4×[El + Tl + Sl]×Al) 
where E, T, and S are erythema, thickness, and scaling, respectively, scored on a scale of 
0 to 4, A is estimated area of skin involved, graded on a scale of 0 to 6, and h, a, t, and l 
are head, arms, trunk, and legs, respectively (range for total score 0 to 72). If any of the 
component scores are missing, the PASI cannot be calculated. 
• PASI-50, PASI-75, PASI-90, PASI-100 = achievement of a 50%, 75%, 90%, or 100% 
reduction in PASI from baseline, respectively.  
• PSD Total Score = sum of the 16 questions (individual questions scored 0 to 10, where 
higher scores indicate more severe symptoms; range for total score 0 to 160). If 1 or more 
items are missing, the score is not calculated.  
• PSD total score of 0 = achievement of a PSD total score of 0.   
• PSD scaling score of 0 = achievement of a PSD scaling score of 0.  
• PSD pain score of 0 = achievement of a PSD pain score of 0.   
• PSD itch score of 0 = achievement of a PSD itch score of 0.  
• PSD Itching/Pain/Scaling Aggregate Score = sum of these 3 questions (individual 
questions that are scored 0 to 10, where higher scores indicate more severe symptoms; 
range for this score is 0 to 30. If 1 or more items are missing, the score is not calculated.   
• PSSI = (erythema score + induration + desquamation) × extent of scalp affected 
(range 0 to 72). Erythema, induration, and desquamation are scored on a scale of 0 to 4, 
where 0 = absent and 4 = severest possible; extent of scale affected is scored on a scale of 
0 to 6, where 0 = 0% of involved area and 6 = 90-100% of involved area. 
• PSSI-50, PSSI-75, PSSI-90, PSSI-100 = achievement of a 50%, 75%, 90%, or 100%   
reduction in PSSI from baseline, respectively.  
 
• Scalpdex Score Transformation = Scalpdex is rated on a 1 to 5 scale which will be 
transformed to 0 to 100 Scale where 1=0; 2=25; 3=50; 4=75; 5=100. This transformed 
score is used to calculate scale scores. 
• Emotions Scale = average of (Q2, Q4, Q5, Q6, Q7, Q9, Q10, Q11, Q12, Q14, Q16, 
Q17, Q19, Q20, Q22) after transforming to 0 to 100 scale as mentioned above. 
Q refers to question number. Q19 will be reverse scored i.e., 1=100; 2=75; 3=50; 
4=25; 5=0. 
• Symptoms Scale = average of (Q1, Q3, Q8) after transforming to 0 to 100 scale as 
mentioned above. Q refers to question number. 
• Functioning Scale = average of (Q13, Q15, Q18, Q21, Q23) after transforming to 
0 to 100 scale as mentioned above. Q refers to question number. 
• Scalpdex Total Score = calculated as mean of all the 23 scalpdex questions using the 
transformed scale of 0 to 100. Q19 will be reverse scored i.e., 1=100; 2=75; 3=50; 4=25; 
5=0 while calculating the mean. Q refers to question number. 


 
Statistical Analysis Plan  
 
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• DLQI Score (Dermatology Life Quality Index for ages 17+ years) = sum of the 10 
questions (individual questions scored as Very much=3, A lot=2, A little=1, Not at all=0, 
with Not relevant recoded to 0; Question 7: Yes=3, No=0, with Not relevant recoded to 0; 
range for score 0 to 30). If 1 item is missing, that item is scored as 0. If 2 or more items 
are missing, the score should not be calculated. 
• CDLQI Score (Children's Dermatology Life Quality Index for ages 12-16 years) = sum 
of the 10 questions (individual questions scored as Very much=3, Quite a lot=2, Only a 
little=1, Not at all=0; Question 7: if the last week was school time, the question was 
scored as Very much=3, Quite a lot=2, Only a little=1, Not at all=0, with Prevented 
school recoded to 3, and if the last week was vacation, the standard responses apply; 
range for score 0 to 30). If 1 item is missing, that item is scored as 0. If 2 or more items 
are missing, the score should not be calculated. 
• Compliance = number of applications divided by the expected number of 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. 
• Number of Expected IP Applications = calculated as last treatment/interruption 
date – first treatment date + 1. If last treatment date ≥ last interruption date, then the 
last treatment date will be used; otherwise, last interruption date will be used in 
deriving the expected number of IP applications. 
• Number of IP Applications = number of expected IP applications – missed IP 
applications as collected in the eCRF. 
• Number of Days on IP = last treatment date – first treatment date + 1. 
• Body Mass Index (BMI) (kg/m2) = (weight in kg)/[(height in cm/100)2]. For Week 8, 
Week 8 height will be used to derive BMI since height is not collected at all visits. 
• BMI Categories 
• Underweight:  BMI < 18.5 
• Normal:           18.5 ≤ BMI ≤ 24.9 
• Overweight:    25.0 ≤ BMI ≤ 29.9 
• Obese:             BMI ≥ 30.0   
• Age Categories: 
• 12 – 17 years  
• 18 – 64 years 
• ≥ 65 years 
• Change from Baseline = value at current time point – value at baseline.  
• Duration (months) since onset of scalp and/or body psoriasis is derived as: 
• (Randomization date – onset date)/30.4375 
• If day of onset is not available, assume that onset occurred on the 1st of the month. 
• Treatment-emergent AE (TEAE) = any AE with an onset date/time after the first 
application of IP. 


 
Statistical Analysis Plan  
 
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• PHQ-8 = sum of the 8 questions (individual questions scored as Not at all=0, Several 
days=1, More than half the days=2, and Nearly every day=3; range for score 0 to 24). If 
more than 1 item is missing, the score should not be calculated.  If 1 item is missing, the 
score is calculated as (sum of answered items*8)/number of answered items. 
• Modified PHQ-A = sum of the 8 questions (individual questions scored as Not at all=0, 
Several days=1, More than half the days=2, and Nearly every day=3, (range for score 0 to 
24). If 1 item is missing, the score should not be calculated.  If 1 item is missing, the 
score is calculated as (sum of answered items*8)/number of answered items. 
• C-SSRS Suicidal Ideation = A “yes” answer at any time during treatment to any 1 of the 
5 suicidal ideation questions (Categories 1-5: Wish to be Dead, Nonspecific Active 
Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent 
to Act, Active Suicidal Ideation with Some Intent to Act, without Specific Plan, and 
Active Suicidal Ideation with Specific Plan and Intent). 
• C-SSRS Suicidal Behavior = A “yes” answer at any time during treatment to any 1 of 
the 5 suicidal behavior questions (Categories 6-10: Preparatory Acts or Behavior, 
Aborted Attempt, Interrupted Attempt, Actual Attempt (nonfatal), Completed Suicide). 
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. 
6.1.8. Data Adjustments/Handling/Conventions 
All collected data will be presented in Clinical Data Interchange Standards Consortium (CDISC) 
datasets. Data not subject to analysis according to this plan will not appear in any tables or 
graphs but will be included only in the CDISC datasets. 
All P values will be displayed in 4 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 25.0 18 March 2022. 
A treatment-related AE is any AE with a relationship to the study drug of possibly, probably, 
likely, 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. 
• 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. 


 
Statistical Analysis Plan  
 
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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. 
6.2. 
Special Handling for COVID-19 Disruptions 
In the event subjects are unable to complete protocol-specific assessments onsite, study sites may 
collect data from subjects remotely via telephone and/or by traditional mail or email. The method 
used for data collection must be clearly documented in the source. Whenever possible, sites 
should adhere to the protocol visit window for remote data collection. Screening and 
Baseline/Day 1 visits/assessments must be performed in the clinic and must NOT be completed 
remotely. If necessary, these visits can be delayed ensuring they are conducted in the clinic and 
not remotely. 
Investigator assessments and subject questionnaires normally completed during on-site visits 
should be completed on the appropriate paper source documents and entered in the EDC. The 
following subject assessments/questionnaires are approved to be collected via 
telemedicine/remotely: 
• C-SSRS 
• PHQ-8/PHQ-A 
• Subject Local Tolerability 
• Adverse Events 
• Concomitant medication 
The following Investigator assessments cannot be completed via telemedicine/remotely: 
• S-IGA 
• B-IGA 
• PASI 


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
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• PSSI 
• BSA 
• Investigator Local Tolerability 
• Subject Weight 
Subjects who were affected by COVID-19 disruptions by either missing their Week 8 visit or 
being discontinued before having a Week 8 visit due to COVID-19 related disruptions will be 
excluded from the mITT population, as described in Section 5. 
7. 
STUDY SUBJECTS AND DEMOGRAPHICS 
7.1. 
Disposition of Subjects and Withdrawals 
Disposition will include tabulations of the number of the screen subjects, the number of screen 
failures, the number of subjects randomized into each treatment group, the number of subjects 
who received treatment, subjects completing study, tabulated reasons for discontinuation from 
the study, including whether 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 database by treatment group and overall. 
A listing of subject’s disposition will be provided. Information on first screening for subjects who 
were rescreened, will be presented under the first screening subject identifier.  
7.2. 
Protocol Deviations 
A data review will be conducted before database lock by the Medical Monitor and the Sponsor to 
identify protocol deviations as important or non-important.   
The number of subjects with important protocol deviations and/or eligibility will be summarized 
for each deviation category by treatment group and overall for the subjects in the ITT population. 
In addition, all the protocol deviations (including important and non-important) associated with 
COVID-19 will be summarized. 
A listing of all protocol deviations will also be provided.  
7.3. 
Demographics and Other Baseline Characteristics 
Summary statistics for age, age category (12-17, 18-64 and ≥ 65 years old), gender (including 
child-bearing potential), race, ethnicity, height, weight, BMI, Fitzpatrick Score,  and baseline 
disease characteristics (duration of scalp/body psoriasis at baseline, % BSA affected by disease, 
S-IGA, B-IGA, PSSI, SI-NRS, WI-NRS, PSD total score, PASI, Scalpdex, DLQI, and CDLQI) 
will be presented by treatment group and overall, using descriptive statistics (continuous results) 
or counts and percentages (categorical results) as appropriate.    
A summary of treatment history, including history of response, intolerance, or contraindication 
to topical corticosteroids and/or topical vitamin D derivatives, Apremilast (Otezla), systematic 
therapy, phototherapy, and psoriasis involvement on knees and/or elbows, face, and genitalia will 
be provided. 


 
Statistical Analysis Plan  
 
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For ordinal variables such as the S-IGA, B-IGA, SI-NRS (average weekly and daily), and WI-
NRS (average weekly and daily), summary statistics including the mean, median, Q1, Q3, 
minimum, and maximum of the ordinal variable will be presented, as well as frequency counts of 
each level of the ordinal variable.   
These analyses will be conducted for the ITT, and Safety populations, except for treatment 
history summary, which will only be summarized on the Safety population.  
A listing of all demographics, analysis population flag, reason not included in the efficacy 
analysis will be provided. 
Medical history for all subjects will be presented in a by-subject listing. 
7.4. 
Exposure and Compliance 
The number of expected IP applications will be summarized by treatment group.  
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 can weight will be summarized descriptively by 
treatment group using continuous methods.    
The number of days on IP will be summarized descriptively by treatment group.  
A subject will be considered compliant with the dosing regimen if the subject applies at least 
80% of the expected applications during the treatment period and does not miss more than 
3 consecutive doses. 
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% 
A listing of drug exposure, compliance and accountability will also be provided. 


 
Statistical Analysis Plan  
 
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8. 
EFFICACY ANALYSIS 
Efficacy analysis will be based on ITT population unless specified otherwise. The randomized 
treatment arm and strata will be used in the efficacy analysis.  
The efficacy analyses that include the stratification factors (pooled sites, baseline S-IGA and 
baseline B-IGA) will use the strata data as collected in the interactive web response system 
(IWRS).  A table of randomized strata vs. actual strata will be provided if there are any 
differences.  
The order of testing for the co-primary and secondary endpoints is discussed in Section 6.1.3. 
Other secondary efficacy endpoints are not included in the testing strategy. 
Data analyzed using CMH methodology will be based upon the following code: 
proc freq data=example noprint; 
  by <visit> ; 
  tables <pooled site group> * <BL S-IGA randomization strata > * <BL B-IGA 
randomization strata > * <treatment>  
         * <outcome> / cmh commonriskdiff(cl=MH) alpha=<0.025 or 0.05>; 
  output out=example_stat cmh; 
run; 
If a non-estimable odds ratio and associated p-value occur as part of the multiple testing strategy, 
the p-value to be used in the testing strategy will be based on a test of a difference in proportions. 
In cases where the odds ratio and difference in proportion are non-estimable, the stratification 
factors will be removed.  Statistical significance will be concluded at the 2.5% significance level 
(2-sided) or less, as discussed in Section 6.1.3. Odds ratios, 95% CIs, and 97.5% CIs for the odds 
ratios and differences in percent will be provided, whenever possible. 
Data analyzed using ANCOVA will be based upon the following code: 
proc mixed data=example; 
  by <visit>; 
  class <treatment> <pooled site group> <BL S-IGA randomization strata > <BL 
B-IGA randomization strata >; 
  model <outcome> = <treatment> <pooled site group> <BL S-IGA randomization 
strata > <BL B-IGA randomization strata > <baseline value> / alpha=<0.025 or 
0.05>; 
  lsmeans trtn / alpha=<0.025 or 0.05> pdiff cl; 
run; 
quit; 
8.1. 
Primary Efficacy Analyses 
The two co-primary efficacy endpoints of S-IGA Success and B-IGA Success at Week 8 will be 
analyzed using ITT population. 
The S-IGA and B-IGA are ordinal scales with 5 severity grades which are reported only in 
integers. Table 4 illustrates the description of each severity grade.  


 
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Table 4: 
S-IGA and B-IGA 
Score Grade 
Description 
0 
Clear 
Plaque thickening = no elevation or thickening over normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red coloration but post-inflammatory 
hyperpigmentation may be present) 
1 
Almost 
Clear 
Plaque thickening = none or possible thickening but difficult to ascertain 
if there is a slight elevation above normal skin level 
Scaling = none or residual surface drying and scaling 
Erythema = light pink coloration 
2 
Mild 
Plaque thickening = slight but definite elevation 
Scaling = fine scales partially or mostly covering the lesions 
Erythema = light red coloration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = most lesions at least partially covered 
Erythema = definite red coloration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with 
hard or sharp edges 
Scaling = non-tenacious or thick tenacious scale, covering most or all of 
lesions 
Erythema = very bright red coloration; extreme red coloration; deep red 
coloration 
 
The co-primary estimands can be described by the following attributes: 
Population: Subjects with Scalp and Body Psoriasis 
Endpoints: S-IGA Success and B-IGA Success 
Treatments: Roflumilast foam 0.3% vs. matching vehicle foam 
Intercurrent events: Over the 8-week randomized treatment period, subjects may be exposed to 
possible known or unknown inter-current events that could impact the estimates of the estimand, 
such as treatment discontinuation due to a specific adverse effect or a lack of effect. A composite 
strategy will be implemented that handles subjects who discontinue due to lack of efficacy or 
adverse event as missing not at random, differently than all other subjects. Subjects who 
discontinue due to lack of efficacy or adverse event will be considered as non-responders (for MI 
and nonresponder imputation analyses) or missing (for observed case analyses) for all analysis 
visits (refer to Section 5.4) on or after the associated analysis visit of the subject’s last dose day 
(refer to Section 6.1.5) 
 The original primary estimand has been left unchanged but re-labeled as a supplemental 
estimand and will handle all intercurrent events using a “Treatment Policy Strategy”, including 
discontinuation due to lack of efficacy or adverse event.  Multiple imputation procedures are 
described in Section 6.1.4.1.2. 
Population-level summary: For this study, the primary population summary will be the ratio of 


 
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the odds of achieving S-IGA/B-IGA success and also the ratio of the odds for B-IGA success at 
Week 8 week using ARQ-154 (roflumilast foam 0.3%), relative to the odds of success at Week 8 
using the matching vehicle foam. An additional estimand will be the between group difference in 
the proportion of subjects achieving S-IGA success and the proportion of subjects achieving B-
IGA success after receiving 8 weeks of ARQ-154 (roflumilast foam 0.3%) or a matching vehicle 
foam.  
Missing data will be imputed as described in Section 6.1.4.  For each imputation dataset, the 
odds ratio will be obtained from CMH test stratified by the randomization factors (pooled site 
group, baseline S-IGA category (3 vs. 4) and baseline B-IGA category (2 vs. ≥ 3)). The 
proportion differences will also be obtained based on stratification factors of baseline S-IGA, 
baseline B-IGA and pooled site group. SAS® PROC MIANALYZE will be used to combine the 
estimates from the imputation datasets (Section 6.1.4). These approaches produce estimates 
which are the combined odds ratio and the proportion difference resulting from adjusting for the 
possible confounding effects of the three classification factors – pooled site group, baseline S-
IGA category (3 vs. 4) and B-IGA category (2 vs. ≥ 3). Randomized stratification factors will be 
used in the efficacy analysis. S-IGA and BIGA will be tested separately, but each endpoint must 
be statistically significant at the 2.5% level for the study to be considered a success.  
8.1.1. Scalp Investigator Global Assessment (S-IGA) 
Categorical Data Analysis 
The first co-primary efficacy endpoint is success in S-IGA of disease severity, defined as an 
S-IGA of “Clear” or “Almost Clear” plus at least a 2-point improvement from baseline at Week 
8. 
The primary endpoint will be analyzed using a CMH test stratified by pooled site group, baseline 
S-IGA stratum, and baseline B-IGA stratum. Statistical significance will be concluded at the 
2.5% significance level (2-sided) or less, as discussed in Section 6.1.3. Odds ratios, 95% CIs, and 
97.5% CIs for the odds ratios will be provided. Additionally, the 95% and 97.5% CIs for 
proportion of successes in each treatment group will be presented using an extension of Wilson’s 
method proposed by Lott and Reider5. Finally, the proportion difference (using Mantel-Haenzsel 
stratum weights and the Sato variance estimator) and 95% and 97.5% CIs of the risk difference 
between roflumilast foam 0.3% and vehicle will be presented. 
For the primary analysis, missing S-IGA scores will be imputed using multiple imputation as 
described in Section 6.1.4.1. 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).  
A tipping point analysis will be performed as described in Section 6.1.4.2. For the tipping point 
analysis, a table will be provided that displays the P values in the analysis against the range of 
shift parameters; included in this table will be the shift parameters, odds ratios, 97.5% CIs, and P 
values for the range of shift parameters to provide information on where the analysis tips from 
significant to non-significant. 


 
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8.1.2. Body Investigator Global Assessment (B-IGA) 
The scale, grade, and description for the B-IGA, is identical to the S-IGA, as discussed in 
Section 8.1.  This endpoint will be analyzed in the same manner as S-IGA (Section 8.1.1). 
8.1.3. Hypothesis Testing  
Primary hypothesis testing will be performed independently on the two co-primary endpoints. The 
null hypothesis is that S-IGA/B-IGA Success at Week 8 does not differ between roflumilast foam 
0.3% and matching vehicle foam. The alternative hypothesis is that the S-IGA/B-IGA Success at 
Week 8 does differ between roflumilast foam 0.3% and matching vehicle foam. 
 
Null Hypothesis (H0): PR QV / PV QR = 1.0,  
Alternative Hypothesis (HA): PR QV / PV QR  ≠ 1.0, where 
 
PR = the proportion of S-IGA/B-IGA Success in roflumilast foam 0.3% 
PV = the proportion of S-IGA/B-IGA Success in matching vehicle foam  
QR = 1 - PR 
QV = 1 – PV. 
 
Each co-primary endpoint will be tested with using 2-sided alpha value of 0.025. The null 
hypotheses of no difference in S-IGA/B-IGA Success at Week 8 between roflumilast foam 0.3% 
and matching vehicle foam will be rejected if the two individual tests are significant. 
8.1.4. Sensitivity and Supplemental Analyses  
The following sensitivity and supplemental analyses will be performed for S-IGA and B-IGA, 
based on the CMH test as described in Sections 8.1.1 and 8.1.2.  Analyses of observed data will 
utilize the same CMH method but will not require the combination of multiple estimates required 
for the analyses with multiple imputation.: 
• The two co-primary efficacy endpoints analyses repeated on subjects in the PP population 
using observed data.   
• The two co-primary efficacy endpoint analyses repeated on subjects in the mITT 
population using MI data.  
• The two co-primary efficacy endpoints analyses repeated on subjects in the ITT 
population using observed data.  
• The two co-primary efficacy endpoints analyses repeated on subjects in the ITT 
population using a non-responder imputation in which the post baseline missing will be 
imputed as non-responder, meaning no S-IGA or B-IGA success.  
• The tipping point analysis as described in Section 6.1.4.2 
• The co-primary efficacy endpoints analyses repeated on subjects in the ITT population 
using MI imputed data, using the CMH model but excluding site as a stratification factor. 


 
Statistical Analysis Plan  
 
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8.1.5. Impact of Site  
The following supportive analysis will be performed to investigate the impact of site on the co-
primary endpoints.  
• To access the impact of pooled site on the primary analysis endpoint, the proportion of 
subjects achieving S-IGA success within each site will be plotted by treatment groups.   
• An additional analysis to examine the impact of pooled study site will examine the 
changes in p-values that occur after removal of a pooled site from the overall analysis.  
First, remove one pooled site from the MI datasets, recalculate the combined CMH p-
value as described for the primary analysis, and repeat removing a different site for each 
iteration. The p-values from the iterations will be plotted by the pooled site removed. 
8.2. 
Secondary Efficacy Analyses 
All secondary efficacy analyses will be performed using the ITT population, unless otherwise 
specified, on both observed and multiple imputation data. The non-responder imputation analysis 
will also be performed for secondary endpoints.  
8.2.1. Scalp Itch – Numeric Rating Scale (SI-NRS) 
The SI-NRS scale ranges from 0 to 10 with 0 being “no scalp itch” and 10 equaling “worst scalp 
itch imaginable.” This will be determined by asking the subject’s assessment of worst scalp itch 
over the past 24 hours.  
Secondary efficacy endpoints relating to SI-NRS are all based on average weekly SI-NRS unless 
specified otherwise. The SPRU4-ITT population will be used for analyses of SI-NRS success. 
For other SI-NRS related endpoints, the ITT population will be used. 
• For the subjects with baseline SI-NRS ≥ 4, achievement of SI-NRS Success at Week 8 
• For the subjects with baseline SI-NRS ≥ 4, achievement of SI-NRS Success at Week 4  
• For the subjects with baseline SI-NRS ≥ 4, achievement of SI-NRS Success at Week 2  
• SI-NRS CFB at Week 1 
• SI-NRS CFB at 72 hours (daily score) 
• SI-NRS CFB at Day 1(daily score) 
SI-NRS Success Analysis 
The estimand attributes (Section 8.1) can be described similarly to those described for the co-
primary endpoints with the exception that the population of interest is changed to subjects with a 
baseline SI-NRS score ≥4.  This endpoint will be analyzed in the same manner as S-IGA 
(Section 8.1.1). 
Change in SI-NRS Score Analysis 
Change from baseline is the primary population level summary for this estimand, and all other 
attributes are identical to those specified for the co-primary endpoints. Percent change from 


 
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baseline is included as a supplemental summary measure.  As specified in Section 2.2.2.2, 
timepoints of primary interest include Day 1 in daily SI-NRS score, 72 hours in daily SI-NRS 
score, and Week 1 in average weekly SI-NRS score. The analysis will include descriptive 
summaries of observed data as well as analyses based on multiple imputation datasets using the 
ITT population.  ANCOVA with terms for pooled site group, baseline S-IGA category, baseline 
B-IGA category, and baseline SI-NRS score as covariates. The LS means, SEs, 95% CIs, 97.5% 
CIs, and P values will be presented. Refer to Section 6.1.4 for additional details.  
Plots of daily SI-NRS (mean and SE of observed value and percent change from baseline) will be 
provided by treatment groups. 
 
Other efficacy endpoints relating to daily SI-NRS  
• Analysis of change and percent from baseline of SI-NRS daily scalp itch assessment will 
be performed using descriptive summaries. This will be summarized by study day.  
• Similar ANCOVA model will be performed for change and percent change from baseline 
daily SI-NRS every day in the first week, at week 2, 4 and 8  
8.2.2. 
Worst Itch – Numeric Rating Scale (WI-NRS) Pruritus Score 
The WI-NRS scale ranges from 0 to 10 with 0 being “no scalp itch” and 10 equaling “worst 
imaginable itch.” This will be determined by asking the subject’s assessment of worst scalp itch 
over the past 24 hours.  
The secondary efficacy endpoint relating to WI-NRS pruritus score, which is based on average 
weekly WI-NRS unless specified otherwise, is:  
• For the subjects with baseline WI-NRS score ≥ 4, achievement of at least 4-point 
improvement from baseline in WI-NRS at Week 8 (“WI-NRS Success at Week 8”) 
WI-NRS Success Analysis 
The estimand attributes (Section 8.1) can be described similarly to those described for the co-
primary endpoints with the exception that the population of interest is the PRU4-ITT population.  
This endpoint will be analyzed in the same manner as S-IGA (Section 8.1.1). 
8.2.3. Psoriasis Area and Severity Index (PASI) 
Psoriasis Area and Severity Index (PASI) is used for the measurement of severity of psoriasis.  
PASI combines the assessment of the severity of lesions and the area affected into a single score 
in the range 0 (no disease) to 72 (maximal disease). 
The secondary efficacy endpoints relating to PASI score are: 
• PASI-75 at Week 8 
• CFB in PASI at Week 2 
PASI-75 Analysis 


 
Statistical Analysis Plan  
 
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The estimand attributes (Section 8.1) can be described similarly to those described for the co-
primary endpoints.  This endpoint will be analyzed in the same manner as S-IGA (Section 8.1.1). 
Change in PASI Score Analysis 
Change in the PASI total score from baseline to Week 2 will be analyzed in the same way as 
change from baseline in SI-NRS (Section 8.2.1).  
8.2.4. Psoriasis Symptoms Diary (PSD) 
The PSD assesses the severity of symptoms or how bothersome are the symptoms of psoriasis. 
The total score combines the scores of the 16 individual questions into a single score in the range 
of 0 to 72 (individual questions scored 0 to 10, where higher scores indicate more severe 
symptoms). 
The secondary efficacy endpoints relating to PSD score are: 
• CFB in PSD Items related to Itching, Pain, and Scaling (Questions 1, 9, and 11) 
aggregate score at Week 8 
• PSD Item related to Scaling (Question 11) = 0 at Week 8 
• PSD Item related to Itching (Question 1) = 0 at Week 8 
• PSD Item related to Pain (Question 9) = 0 at Week 8 
• PSD Total Score = 0 at Week 8 
Change in Total PSD Score Analysis 
Change in the PSD  score from baseline to Week 2, 4, and 8 will be analyzed in the same way as 
change from baseline in SI-NRS (Section 8.2.1).  
The occurrence of PSD itching, scaling, pain, and total scores of 0 will be analyzed with methods 
previously described for the primary efficacy endpoints (Section 8.1.1).    
8.2.5. Psoriasis Scalp Severity Index (PSSI) 
The PSSI is used to measure the severity of psoriasis, combining the assessment of the severity 
of scalp lesions and the area of scalp affected into a single score ranging from 0 (no disease) to 
72 (maximal disease).  
The secondary efficacy endpoint relating to PSSI score is: 
• PSSI-75 at Week 8 
PSSI-75 Analysis 
The estimand attributes (Section 8.1) can be described similarly to those described for the co-
primary endpoints.  This endpoint will be analyzed in the same manner as S-IGA (Section 8.1.1). 


 
Statistical Analysis Plan  
 
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8.2.6. Scalp Investigator Global Assessment (S-IGA) 
The secondary efficacy endpoints relating to S-IGA score are: 
• S-IGA score of “Clear” at Week 8 
• S-IGA Success at Week 4 
• S-IGA Success at Week 2 
S-IGA Categorical Analysis 
The estimand attributes (Section 8.1) can be described similarly to those described for the co-
primary endpoints.  This endpoint will be analyzed in the same manner as S-IGA (Section 8.1.1). 
A summary of primary and secondary efficacy analyses is shown in Table 5. 
 
Table 5: 
Summary of Primary and Secondary Efficacy Analyses 
Efficacy Endpoint 
Primary Analysis 
Sensitivity or Supplemental Analysis 
Primary (α = 0.025) 
S-IGA Success  
(IGA score of ‘0’ or ‘1’ 
plus at least 2-point 
improvement from 
baseline) at week 8 
ITT, multiple 
imputation (CMH) 
#1 PP, observed data (CMH) 
#2 mITT, multiple imputation (CMH) 
#3 ITT, observed data (CMH) 
#4 ITT, non-responder imputation (CMH) 
#5 ITT, Tipping point 
#6 ITT based on different site pooling 
strategy 
#7 ITT without site stratification 
B-IGA Success  
(IGA score of ‘0’ or ‘1’ 
plus at least 2-point 
improvement from 
baseline) at week 8 
ITT, multiple 
imputation (CMH) 
#1 PP, observed data (CMH) 
#2 mITT, multiple imputation (CMH) 
#3 ITT, observed data (CMH) 
#4 ITT, non-responder imputation (CMH) 
#5 ITT, Tipping point 
#6 ITT based on different site pooling 
strategy 
#7 ITT without site stratification 
Secondary Family 2 (α=0.005) 


 
Statistical Analysis Plan  
 
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Family 1 (α=0.01 or 
0.015): 
Average weekly SI-NRS 
Success (achievement of 
at least a 4-point 
improvement) at Weeks 
2, 4, 8 
SPRU4-ITT 
population, multiple 
imputation (CMH, 
odds ratio) 
#1 SPRU4-ITT, observed data (CMH) 
#2 SPRU4-ITT, non-responder 
imputation (CMH) 
 
Family 1 (α=0.01 or 
0.015): 
• SI-NRS change 
from baseline at 
Week 1 
• SI-NRS change 
from baseline at 
72 hours 
•  
ITT population, 
multiple imputation, 
ANCOVA  
#1 ITT, observed data  
Family 2 (α=0.005): 
Average weekly WI-
NRS Success 
(achievement of at least 
a 4-point improvement) 
at Week 8 
PRU4-ITT, multiple 
imputation (CMH) , 
odds ratio) 
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.005): 
PASI-75 at Week 8 
 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 2 (α=0.005): 
CFB in PSD Items 
related to Itching, Pain, 
and Scaling (Questions 
1, 9, and 11) aggregate 
score at Week 8 
ITT, multiple 
imputation, 
ANCOVA 
#1 ITT, observed data  
 
Family 2 (α=0.005): 
• PSD Item related 
to Scaling 
(Question 11) = 0 
at Week 8 
• PSD Item related 
to Itching 
(Question 1) = 0 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 


 
Statistical Analysis Plan  
 
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at Week 8 
• PSD Item related 
to Pain (Question 
9) = 0 at Week 8 
 
Family 2 (α=0.005): 
PSSI-75 at week 8 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 3 (α=0.01 or 0.02 
or 0.025): 
S-IGA score of ‘Clear’ at 
Week 8 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 3 (α=0.01 or 0.02 
or 0.025): 
S-IGA success at week 
4, 2 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 3 (α=0.01 or 0.02 
or 0.025): 
Change from baseline in 
PASI at week 2 
ITT, multiple 
imputation, 
ANCOVA  
#1 ITT, observed data 
Family 3 (α=0.01 or 0.02 
or 0.025): 
PSD Total Score = 0 at 
Week 8 
ITT, multiple 
imputation (CMH)  
#1 ITT, observed data (CMH) 
#2 ITT, non-responder imputation (CMH) 
Family 3 (α=0.01 or 0.02 
or 0.025): 
SI-NRS change from 
baseline at Day 1 
ITT population, 
multiple imputation, 
ANCOVA  
#1 ITT, observed data  
8.3. 
Other Efficacy Analyses 
Analyses of other secondary efficacy endpoints will be performed for the ITT population.    
Table 6 provides a summary of analyses of other efficacy endpoints that were not included in the 
multiple testing strategy.  
Table 6: 
Summary of Analyses of Other Efficacy Endpoints 
Endpoint 
Missing Data Approach 
Analysis 
Method 
S-IGA  


 
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Endpoint 
Missing Data Approach 
Analysis 
Method 
S-IGA score of “Clear” at Weeks 2 and 4 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change from baseline in S-IGA at Weeks 
2, 4, and 8 (Observed Data) 
Observed Data 
 Summary 
Statistics 
B-IGA 
B-IGA success at Weeks 2 and 4 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
B-IGA score of “Clear” at Weeks 2, 4, 
and 8  
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
B-IGA score of “Clear” or “Almost 
Clear” at Weeks 2, 4, and 8 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change from baseline in B-IGA at Weeks 
2, 4, and 8 (Observed Data) 
Observed Data 
Summary 
Statistics 
SI-NRS 
SI-NRS Success at Weeks 1, 3, 5, 6, and 7 Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change and percent change from baseline 
in SI-NRS at Weeks 2, 3, 4, 5, 6, 7, and 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
WI-NRS 
WI-NRS Success at Weeks 1, 3, 5, 6, and 
7 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change and percent change from baseline 
in WI-NRS at Weeks 1, 2, 3, 4, 5, 6, 7, 
and 8 
Observed Data 
ANCOVA 


 
Statistical Analysis Plan  
 
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Endpoint 
Missing Data Approach 
Analysis 
Method 
PASI 
PASI-75, at Weeks 2 and 4 and PASI-50, 
PASI-90, and PASI-100 at Weeks 2, 4, 
and 8 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change from baseline in PASI at Weeks 4 
and 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
Percent change from baseline in PASI at 
Weeks 2, 4, and 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
PSSI 
PSSI-75 at Weeks 2 and 4 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
PSSI-50, PSSI-90, and PSSI-100 at 
Weeks 2, 4, and 8 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change and percent change from baseline 
in PSSI at Weeks 2, 4, and 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
PSD 
Change and percent change from baseline 
in PSD total score at Weeks 2, 4, and 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
Change and percent change from baseline 
in an aggregate score 3 PSD individual 
items dealing with Itching, Pain, and 
Scaling at Weeks 2 and 4.   
Multiple Imputation and 
Observed Data 
ANCOVA 
Percent change from baseline in an 
aggregate score 3 PSD individual items 
dealing with Itching, Pain, and Scaling at 
Week 8 
Multiple Imputation and 
Observed Data 
ANCOVA 
PSD Item related to Itching (Question 1) 
= 0 at Weeks 2 and 4 
PSD Item related to Scaling (Question 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 


 
Statistical Analysis Plan  
 
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Endpoint 
Missing Data Approach 
Analysis 
Method 
11) = 0 at Weeks 2 and 4 
PSD Item related to Pain (Question 9) = 0 
at Weeks 2 and 4 
Achievement of PSD Total Score=0 at 
Weeks 2 and 4 
Multiple Imputation, 
Observed Data, Non-
responder Imputation 
CMH 
Change and percent change from baseline 
in PSD individual item scores at Week 2, 
4, and 8  
Observed Data 
ANCOVA 
Scalpdex 
Change and percent change from baseline 
in Scalpdex total score as well as the 
emotions, symptoms, and functioning 
scales at Weeks 2, 4, and 8 
Observed Data 
ANCOVA 
DLQI/CDLQI 
Change and percent change from baseline 
in Dermatology Life Quality Index 
(DLQI)/ Children’s DLQI (CDLQI) total 
scores at Weeks 2, 4, and 8 
Observed Data 
ANCOVA 
% BSA Affected by Psoriasis 
Change and percent change from baseline 
in total body % BSA affected by psoriasis 
at Weeks 2, 4, and 8 
Observed Data 
ANCOVA 
Extent of Scalp Involvement 
Change and percent change from baseline 
in percent of scalp affected by psoriasis at 
Weeks 2, 4, and 8 
Observed Data 
Summary 
Statistics 
The other secondary efficacy endpoints are listed in Section 2.2.2.3. Categorical endpoints will 
be analyzed with methods similar to those described for the sensitivity and supplemental 
analyses of S-IGA and B-IGA (Section 8.1. Methods for analyses of change and percent change 
from baseline are described in Section 8.2.3. Table 6 identifies the methods used to handle 
missing data and the analysis method.  The same methods used for the primary and sensitivity 
analyses of the primary endpoints will be used.  For these other efficacy endpoints, p-values will 


 
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be presented outside of the multiple testing paradigm, and therefore should be interpreted with 
caution. 
8.4. 
Subgroup Analyses of Efficacy Variables 
For the co-primary endpoints, S-IGA success at Week 8 and B-IGA success at Week 8, subgroup 
analysis will be performed on the following using the primary estimand: 
• Topical Corticosteroids – Inadequate Response, intolerance, or contraindication (Y/N) 
• Topical Vitamin D derivatives –- Inadequate Response, intolerance, or contraindication 
(Y/N) 
• Age categories (12-17, 18-64, ≥ 65) 
• B-IGA at baseline (2, ≥3 based on data entered in EDC) 
• S-IGA at baseline (3 – Moderate, 4 – Severe based on data entered in EDC) 
• Gender (male, female) 
• Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
• Race (White, Black or African American, Others) 
• Fitzpatrick score of I-III vs IV-VI 
• Subjects with facial involvement 
• Subjects with genitalia involvement 
• Subjects with knee involvement 
• Subjects with elbow involvement 
• Subjects with knee or elbow involvement 
The above subgroup analyses are generated with imputed data only. Methods will be similar to 
those used for the primary analysis of the endpoint. Baseline B-IGA/S-IGA will be removed 
from the CMH model for analyses by the Baseline B-IGA/S-IGA subgroups, respectively. Forest 
plots will be produced for the odds ratio point estimates and associated 95% confidence 
intervals, as well as for the and difference in proportions point estimate and associated 95% 
confidence intervals.  The forest plots will include the overall results (point estimate and 95% 
confidence interval) along with vertical reference lines at 1 (odds ratio) or 0 (difference in 
proportions) as well as another vertical reference line at the point estimate for the overall ITT 
population.  
 
9. 
SAFETY AND TOLERABILITY ANALYSIS 
Safety will be evaluated from reported AEs, physical examinations, local tolerance assessments, 
changes in clinical laboratory values, changes in vital signs/weight, C-SSRS, PHQ-8, and 
modified PHQ-A results. No inferential statistical tests will be performed. 
All safety analyses will be performed on the Safety population. 


 
Statistical Analysis Plan  
 
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9.1. 
Adverse Events 
An overall summary of TEAEs will be provided; this will present number and percent of subjects 
who reported at least 1: TEAE (including all TEAEs, TEAEs by maximum severity, and TEAEs 
by greatest relationship), treatment emergent serious adverse events (TESAEs), TEAE leading to 
discontinuation of the study drug, TEAE leading to study discontinuation, and TEAE resulting in 
death. 
Tables including the number and percentage of subjects will be provided for the following 
categories: 
1. TEAEs by SOC and PT 
2. TEAEs by SOC, PT and Maximum Severity  
3. TEAEs by SOC, PT, and Strongest Relationship to Study Drug (i.e., related vs. unrelated) 
4. TEAEs by PT in descending order 
5. TESAE by SOC and PT 
6. TEAE leading to discontinuation of the study drug by SOC and PT 
7. TEAE leading to study discontinuation by SOC and PT 
In the summaries showing severity and relationship to study medication the event with the 
maximum severity (mild < moderate < severe) or strongest relationship (not related < 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 = likely). 
In the AE data listings, all AEs will be displayed. AEs that are treatment emergent will be 
flagged and AE occurred in the application site will be flagged.  
Most frequent TEAE (≥ 1%) of PT will be plotted by treatment groups along with overall 
incidence of TEAEs and overall incidence of TESAEs.   
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, SOC, and preferred term will be prepared for the Safety 
population. Additionally, this table will be repeated for TEAEs leading to withdrawal from the 
study. No inferential statistical tests will be performed.  
9.1.2. Deaths and Serious Adverse Events 
Any deaths that occur during the study will be flagged in the AE listing. 


 
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9.2. 
Local Tolerability Assessments 
The investigator’s assessment of the application site reaction will be summarized by study visit 
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, change and percent change from baseline values for continuous hematology, 
chemistry, and urinalysis results. Categorical urinalysis results will be summarized using 
frequencies by study visit and treatment. 
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 (shift table). 
Abnormal results will be flagged in the listings.  
9.4. 
Vital Signs 
Descriptive summaries of observed values, changes from baseline, and percent 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 and visit.   
The number of subjects who gain or lose ≥ 5% of their baseline body weight during the course of 
the study, as well as subjects who gain or lose ≥10% of their baseline body weight over the 
course of the study, will be summarized by treatment group. This summary will be repeated by 
intentionality of weight loss (intentional or unintentional, as captured on the eCRF). 
Shift tables for subjects who shift from their baseline BMI category as defined in Section 6.1.7 
(underweight, normal, overweight, obese) to a different BMI category throughout the course of 
the study will be provided by treatment group and visit. This summary will be repeated by 
intentionality of weight loss (intentional or unintentional, as captured on the eCRF). 
9.5. 
PHQ-8 and Modified PHQ-A 
Data for PHQ-8 and modified PHQ-A will be classified using each subject’s total score at a time 
point into a category based on the following scoring system:  
• None – Minimal depression (0 to 4) 
• Mild depression (5 to 9) 
• Moderate depression (10 to 14) 
• Moderately severe depression (15 to 19) 
• Severe depression (20 to 24) 


 
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Shift tables showing the category of severity at each visit by treatment group will be presented. 
9.6. 
C-SSRS 
The C-SSRS is a questionnaire that prospectively assesses Suicidal Ideation and Suicidal 
Behavior. At the Screening study visit, “Baseline/Screening” version of the C-SSRS will be 
used. This version assesses Suicidal Ideation and Suicidal Behavior during the subject’s lifetime 
and during the past 6 months. For the Screening visit, “lifetime” experience of the subject with 
Suicidal Ideation and Suicidal Behavior will be summarized. For baseline visit, the “Since Last 
Visit” version will be used. 
Tables will include results from the Suicidal Ideation and Suicidal Behavior sections of the C-
SSRS. Frequencies and percentages of subjects with a response of “Yes” at any point on the 
Suicidal Ideation and Suicidal Behavior items will be summarized by study visit and treatment 
group. 
9.7. 
Concomitant Medication 
Prior and concomitant medications will be summarized descriptively by treatment, 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 prior to 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. 
Medications will be coded using World Health Organization (WHO) Drug Global B3, version 
March 2022. 
9.8. 
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. 
10. 
OTHER PLANNED ANALYSIS 
10.1. Pharmacokinetic Analysis 
All PK collection information from the eCRF, along with PK concentrations, will be presented in 
a listing. Concentration data will be summarized by study visit and treatment group using 
summary statistics.  Sample values reported below the limit of quantification (BLQ) will be set 
equal to zero for plasma descriptive statistics.  The lower limit of quantification (LLOQ) is 0.100 
ng/mL for roflumilast and the N-oxide metabolite.  For the analysis of the pre-dose plasma 
concentrations only, to allow for the calculation of geometric mean, 0.0001 will be added to all 
concentration values to remove all zero values.  Addition of 0.0001 will only be necessary if 
there are 1 or more values BLQ. 


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
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11. 
CHANGES FROM PLANNED ANALYSIS 
11.1. Version 2.0 
All the exploratory endpoints have been added in the SAP, but they were not specified in the 
protocol. 
The following analysis populations have been added: 
• The SPRU4-ITT population has been added to facilitate interpretation of the SI-NRS 
analysis in addition to the ITT population; and 
• The PRU4-ITT population has been added to facilitate interpretation of the WI-NRS 
analysis in addition to the ITT population.  
These populations are not discussed in the protocol.  
In this SAP, PK population is defined as subjects who received at least one confirmed dose of 
investigational product (IP) and provided at least one PK sample. This population will be used 
for summary of PK concentration results. The definition is different from that in protocol where 
PK population is defined as subjects receiving active drug with sufficient plasma concentrations 
of roflumilast to define a profile, as determined by the pharmacokineticist, which will be used for 
analysis of PK parameters. 
Version 2.0 of the SAP is based on the final version of Amendment 3 for the ARQ-154-309 
protocol dated 29-Jul-2022. At the time of signing this SAP version 2.0, the protocol is approved 
and in the process of being published. 
11.2. Version 3.0 
Section 1 Overview provides a description of the rationale for SAP Version 3.  The purpose of 
the SAP is to document the change to the primary estimand and related multiple imputation 
strategies. The revised estimand will be the focus of the Clinical Study Report and NDA.  Key 
results based on the original estimand defined in SAP versions 1 and 2 will be provided as 
supplemental information for the primary and secondary endpoints covered by the multiple 
testing strategy. This change to the primary estimand and multiple imputation procedure was 
based on recommendations from FDA during a pre-NDA meeting for a similar program held on 
14Sep2022. 
12. 
REFERENCES 
1. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998. 
2. ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2016. http://www.amstat.org/about/ethicalguidelines.cfm 
3. RSS. (2014) The Royal Statistical Society: Code of Conduct, 2014. 
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf. 


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
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4. 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 
5. Lott, A and Reiter, J.P. (2020), “Wilson Confidence Intervals for Binomial Proportions With 
Multiple Imputation for Missing Data,” The American Statistician, 74:2, 109-115  
 
 


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
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14. 
TABLES, LISTINGS AND FIGURES 
All listings, tables, and graphs 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 (listing number).  
14.1. Planned Table Descriptions  
The following are planned summary tables for protocol number ARQ-154-309. The table numbers are place holders 
only and may be changed when the tables are produced.  
 
Table Number  
Population 
Table Title/Summary 
14.1 
Disposition, Baseline Characteristics and Exposure Summary 
14.1.1 
 All Subjects 
Subject Disposition 
14.1.2.1 
ITT  
Demographics and Baseline Characteristics 
14.1.2.1 (cont.) 
ITT  
Demographics and Baseline Characteristics 
 
 
 
14.1.2.1 (cont.) 
ITT  
Demographics and Baseline Characteristics 
14.1.2.1 (cont.) 
ITT  
Demographics and Baseline Characteristics 
14.1.2.1 (cont.) 
ITT  
Demographics and Baseline Characteristics 
14.1.2.1 (cont.) 
ITT  
Demographics and Baseline Characteristics 
14.1.2.2 
Safety  
Demographics and Baseline Characteristics 
14.1.3 
Safety  
Previous Treatment History of Scalp and Body Psoriasis 
14.1.4 
ITT  
Protocol Deviations 
14.1.5 
Safety  
Prior Medications by Anatomic Therapeutic Chemical (ATC) Class Level 4 
and Preferred Term 
14.1.6 
Safety  
Summary of Study Drug Exposure 
14.2 
Efficacy Summary 
14.2.1 
ITT, SPRU4-
ITT, or PRU4-
ITT 
Hypothesis Testing for Primary and Secondary Efficacy Endpoints - 
Multiple Imputation 
14.2.1.1 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Primary Analysis) Categorical Results  
14.2.1.1.s 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Primary Analysis, Supplemental 
Estimand) Categorical Results  
14.2.1.2 
mITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Sensitivity Analysis) Categorical 
Results  
14.2.1.3 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Observed Data (Sensitivity Analysis) Categorical Results  
14.2.1.4 
Per-protocol  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Observed Data  (Supplemental Analysis) Categorical Results  
14.2.1.5 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Non-responder Imputation (Sensitivity Analysis) Categorical 
Results  
14.2.1.6 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success at 
Week 8 – Tipping Point Analysis (Sensitivity Analysis) Categorical Results  


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
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14.2.1.7 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit – Multiple Imputation, without Site Stratification (Sensitivity 
Analysis) Categorical Results 
14.2.1.8.1 
ITT  
Scalp Investigator Global Assessment (S-IGA) Success at Week 8 – 
Multiple Imputation, Impact of Site (Supporting Analysis) 
14.2.1.8.2 
ITT  
Scalp Investigator Global Assessment (S-IGA) Success at Week 8 by Site – 
Observed Data (Supporting Analysis) 
14.2.1.9.1 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Response to Topical Corticosteroids – Multiple Imputation 
(Subgroup Analysis) 
14.2.1.9.2 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Age Group – Multiple Imputation (Subgroup Analysis) 
14.2.1.9.3 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Baseline S-IGA Disease Severity – Multiple Imputation 
(Subgroup Analysis) 
14.2.1.9.4 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit by Study Visit and Baseline B-IGA Disease Severity – Multiple 
Imputation (Subgroup Analysis) 
14.2.1.9.5 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Gender – Multiple Imputation (Subgroup Analysis) 
14.2.1.9.6 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Ethnicity – Multiple Imputation (Subgroup Analysis) 
14.2.1.9.7 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Race – Multiple Imputation (Subgroup Analysis) 
14.2.1.9.8 
ITT  
Scalp Investigator Global Assessment (S-IGA)  Grades and Success by 
Study Visit and Fitzpatrick Score – Multiple Imputation (Subgroup 
Analysis) 
14.2.1.9.9 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Facial Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.1.9.10 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Genitalia Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.1.9.11 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Knee Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.1.9.12 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Elbow Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.1.9.13 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Knee or Elbow Involvement – Multiple Imputation 
(Subgroup Analysis) 
14.2.1.9.14 
ITT  
Scalp Investigator Global Assessment (S-IGA) Grades and Success by 
Study Visit and Response to Topical Vitamin D Derivatives – Multiple 
Imputation (Subgroup Analysis) 
14.2.1.10  
ITT  
Summary, Change, and Percent Change from Baseline in Scalp Investigator 
Global Assessment (S-IGA) by Study Visit – Observed 
Data                                                                                                                     
14.2.2.1 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Primary Analysis) Categorical Results 
14.2.2.1.s 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Primary Analysis, Supplemental 
Estimand) Categorical Results  


 
Statistical Analysis Plan  
 
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Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
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14.2.2.2 
mITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Multiple Imputation (Sensitivity Analysis) Categorical 
Results 
14.2.2.3 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit– Observed Data(Sensitivity Analysis) Categorical Results 
14.2.2.4 
Per-Protocol  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Observed Data (Supplemental Analysis) Categorical Results 
14.2.2.5 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Non-responder Imputation (Sensitivity Analysis) Categorical 
Results 
14.2.2.6 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success at 
Week 8 – Tipping Point Analysis (Sensitivity Analysis) Categorical Results 
14.2.2.7 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit – Multiple Imputation, without Site Stratification (Sensitivity 
Analysis) Categorical Results 
14.2.2.8.1 
ITT  
Body Investigator Global Assessment (B-IGA) Success at Week 8 – 
Multiple Imputation, Impact of Site (Supporting Analysis) 
14.2.2.8.2 
ITT  
Body Investigator Global Assessment (B-IGA) Success at Week 8 by Site – 
Observed Data (Supporting Analysis) 
14.2.2.9.1 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Response to Topical Corticosteroids – Multiple Imputation 
(Subgroup Analysis) 
14.2.2.9.2 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit by Study Visit and Age Group – Multiple Imputation 
(Subgroup Analysis) 
14.2.2.9.3 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Baseline S-IGA Disease Severity – Multiple Imputation 
(Subgroup Analysis) 
14.2.2.9.4 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Baseline B-IGA Disease Severity – Multiple Imputation 
(Subgroup Analysis) 
14.2.2.9.5 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Gender – Multiple Imputation (Subgroup Analysis) 
14.2.2.9.6 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Ethnicity – Multiple Imputation (Subgroup Analysis) 
14.2.2.9.7 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Race – Multiple Imputation (Subgroup Analysis) 
14.2.2.9.8 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Fitzpatrick Score – Multiple Imputation (Subgroup 
Analysis) 
14.2.2.9.9 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Facial Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.2.9.10 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Genitalia Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.2.9.11 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Knee Involvement – Multiple Imputation (Subgroup 
Analysis) 
14.2.2.9.12 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Elbow Involvement – Multiple Imputation (Subgroup 
Analysis) 


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 57 of 63 
14.2.2.9.13 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Knee or Elbow Involvement – Multiple Imputation 
(Subgroup Analysis) 
14.2.2.9.14 
ITT  
Body Investigator Global Assessment (B-IGA) Grades and Success by 
Study Visit and Response to Topical Vitamin D Derivatives – Multiple 
Imputation (Subgroup Analysis) 
14.2.2.10 
ITT  
Summary, Change, and Percent Change from Baseline in Body Investigator 
Global Assessment (B-IGA) by Study Visit – Observed Data 
 
 
 
 
 
 
14.2.3.1 
SPRU4-ITT  
Average Weekly Scalp Itch–Numeric Rating Scale (SI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis)  
14.2.3.1.s 
SPRU4-ITT  
Average Weekly Scalp Itch–Numeric Rating Scale (SI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis, Supplemental 
Estimand)  
14.2.3.2 
SPRU4-ITT  
Average Weekly Scalp Itch–Numeric Rating Scale (SI-NRS) Success by 
Study Visit – Observed Data (Sensitivity Analysis) 
14.2.3.3 
SPRU4-ITT  
Average Weekly Scalp Itch–Numeric Rating Scale (SI-NRS) Success by 
Study Visit - Non-responder Imputation (Sensitivity Analysis)  
14.2.3.4 
ITT  
Average Weekly Scalp Itch-Numeric Rating Scale (SI-NRS) by Study Visit 
– Multiple Imputation (ANCOVA)  
14.2.3.5 
ITT  
Summary, Change, and Percent Change of Average Weekly Scalp Itch-
Numeric Rating Scale (SI-NRS) by Study Visit – Multiple Imputation  
14.2.3.6 
ITT  
Average Weekly Scalp Itch-Numeric Rating Scale (SI-NRS) by Study Visit 
– Observed Data (ANCOVA)  
14.2.3.7 
ITT  
Summary, Change, and Percent Change of Average Weekly Scalp Itch-
Numeric Rating Scale (SI-NRS) by Study Visit – Observed Data  
14.2.3.8 
ITT  
Daily Scalp Itch-Numeric Rating Scale (SI-NRS) for Day 1 (24-hour) and 
72-hour Endpoints – Multiple Imputation (ANCOVA)   
14.2.3.9 
ITT  
Summary, Change, and Percent Change of Daily Scalp Itch-Numeric 
Rating Scale (SI-NRS) by Study Day – Multiple Imputation  
14.2.4.1 
PRU4-ITT  
Average Weekly Worst Itch–Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis)  
14.2.4.1.s 
PRU4-ITT  
Average Weekly Worst Itch–Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Multiple Imputation (Primary Analysis, Supplemental 
Estimand)  
14.2.4.2 
PRU4-ITT  
Average Weekly Worst Itch–Numeric Rating Scale (WI-NRS) Success by 
Study Visit – Observed Data (Sensitivity Analysis)  
14.2.4.3 
PRU4-ITT  
Average Weekly Worst Itch–Numeric Rating Scale (WI-NRS) Success by 
Study Visit - Non-responder Imputation (Sensitivity Analysis)  
14.2.4.4 
ITT  
Summary, Change, and Percent Change of Average Weekly Worst Itch-
Numeric Rating Scale (WI-NRS) by Study Visit – Observed Data  
14.2.4.5 
ITT  
Summary, Change, and Percent Change of Daily Worst Itch-Numeric 
Rating Scale (WI-NRS) by Study Day – Observed Data  
14.2.4.6 
ITT  
Average Weekly Worst Itch-Numeric Rating Scale (WI-NRS) by Study 
Visit– Observed Data (ANCOVA)  
14.2.4.7 
ITT  
Daily Worst Itch-Numeric Rating Scale (WI-NRS) by Study Day – 
Observed Data (ANCOVA)  
14.2.5.1 
ITT  
Achievement of Psoriasis Area and Severity Index (PASI-75, PASI-90, 
PASI-50, PASI-100) by Study Visit – Visit–Multiple Imputation  
14.2.5.2 
ITT  
Achievement of Psoriasis Area and Severity Index (PASI-75, PASI-90, 
PASI-50) by Study Visit – Observed Data  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 58 of 63 
14.2.5.3 
ITT  
Achievement of Psoriasis Area and Severity Index (PASI-75, PASI-90, 
PASI-50) by Study Visit – Non-responder Imputation (Sensitivity 
Analysis) Categorical Results  
14.2.5.4 
ITT  
Summary of Psoriasis Area and Severity Index (PASI) by Study Visit – 
Multiple Imputation (ANCOVA)  
14.2.5.5 
ITT  
Summary, Change and Percent Change from Baseline in Psoriasis Area and 
Severity Index (PASI) by Study Visit - Multiple Imputation  
14.2.5.6 
ITT  
Summary of Psoriasis Area and Severity Index (PASI) by Study Visit – 
Observed Data (ANCOVA)  
14.2.5.7 
ITT  
Summary, Change and Percent Change from Baseline in Psoriasis Area and 
Severity Index (PASI) by Study Visit – Observed Data  
14.2.6.1 
ITT  
Achievement of Psoriasis Scalp Severity Index (PSSI-75, PSSI-50, PSSI-
90, PSSI-100) by Study Visit – Multiple Imputation  
14.2.6.1.s 
ITT  
Achievement of Psoriasis Scalp Severity Index (PSSI-75, PSSI-50, PSSI-
90, PSSI-100) by Study Visit – Multiple Imputation (Secondary Analysis, 
Supplemental Estimand)   
14.2.6.2 
ITT  
Achievement of Psoriasis Scalp Severity Index (PSSI-75, PSSI-50, PSSI-
90, PSSI-100) by Study Visit – Observed Data  
14.2.6.3 
ITT  
Achievement of Psoriasis Scalp Severity Index (PSSI-75, PSSI-90, PSSI-
50, PSSI-100) by Study Visit – Non-responder Imputation (Sensitivity 
Analysis) Categorical Results  
14.2.6.4 
ITT  
Summary of Psoriasis Scalp Severity Index (PSSI) by Study Visit – 
Multiple Imputation (ANCOVA)  
14.2.6.5 
ITT  
Summary, Change and Percent Change from Baseline in Psoriasis Scalp 
Severity Index (PSSI) by Study Visit - Multiple Imputation  
14.2.6.6 
ITT  
Summary of Psoriasis Scalp Severity Index (PSSI) by Study Visit – 
Observed Data (ANCOVA)  
14.2.6.7 
ITT  
Summary, Change and Percent Change from Baseline in Psoriasis Scalp 
Severity Index (PSSI) by Study Visit – Observed Data  
14.2.7.1.1 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) Aggregate Score of 
Itching/Pain/Scaling by Study Visit – Multiple Imputation (ANCOVA)  
14.2.7.1.1.s 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) Aggregate Score of 
Itching/Pain/Scaling by Study Visit – Multiple Imputation (ANCOVA) 
(Secondary Analysis, Supplemental Estimand) 
14.2.7.1.2 
ITT  - Patients 
with Age ≥18 
years 
Summary, Change, and Percent Change from Baseline in Psoriasis 
Symptoms Diary (PSD) Aggregate Score of Itching/Pain/Scaling by Study 
Visit – Multiple Imputation  
14.2.7.1.3 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) Aggregate Score of 
Itching/Pain/Scaling by Study Visit – Observed Data (ANCOVA)  
14.2.7.1.4 
ITT  - Patients 
with Age ≥18 
years 
Summary, Change, and Percent Change from Baseline in Psoriasis 
Symptoms Diary (PSD) Aggregate Score of Itching/Pain/Scaling by Study 
Visit – Observed Data  
14.2.7.2.1 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Scaling by Study Visit – Multiple Imputation   
14.2.7.2.1.s 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Scaling by Study Visit – Multiple Imputation (Secondary 
Analysis, Supplemental Estimand)  
14.2.7.2.2 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Scaling by Study Visit – Observed Data (Sensitivity Analysis)  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 59 of 63 
14.2.7.2.3 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Scaling by Study Visit – Non-responder Imputation (Sensitivity 
Analysis)  
14.2.7.3.1 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Itching by Study Visit – Multiple Imputation   
14.2.7.3.1.s 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Itching by Study Visit – Multiple Imputation (Secondary 
Analysis, Supplemental Estimand)   
14.2.7.3.2 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Itching by Study Visit – Observed Data (Sensitivity Analysis)  
14.2.7.3.3 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Itching by Study Visit – Non-responder Imputation (Sensitivity 
Analysis)  
14.2.7.4.1 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Pain by Study Visit – Multiple Imputation   
14.2.7.4.1.s 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Pain by Study Visit – Multiple Imputation (Secondary Analysis, 
Supplemental Estimand)  
14.2.7.4.2 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Pain by Study Visit – Observed Data (Sensitivity Analysis)  
14.2.7.4.3 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Item 
Related to Pain by Study Visit – Non-responder Imputation (Sensitivity 
Analysis)  
14.2.7.5.1 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Total 
Score by Study Visit – Multiple Imputation   
14.2.7.5.1.s 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Total 
Score by Study Visit – Multiple Imputation (Secondary Analysis, 
Supplemental Estimand)  
14.2.7.5.2 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Total 
Score by Study Visit – Observed Data (Sensitivity Analysis)  
14.2.7.5.3 
ITT  - Patients 
with Age ≥18 
years 
Achievement of Score of 0 for Psoriasis Symptoms Diary (PSD) Total 
Score by Study Visit – Non-responder Imputation (Sensitivity Analysis)  
14.2.7.6.1 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) by Study Visit – Multiple 
Imputation (ANCOVA)  
14.2.7.6.2 
ITT  - Patients 
with Age ≥18 
years 
Summary, Change and Percent Change from Baseline in Psoriasis 
Symptoms Diary (PSD) by Study Visit – Multiple Imputation  
14.2.7.6.3 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) by Study Visit – Observed 
Data (ANCOVA)  
14.2.7.6.4 
ITT  - Patients 
with Age ≥18 
years 
Summary, Change and Percent Change from Baseline in Psoriasis 
Symptoms Diary (PSD) by Study Visit – Observed Data  
14.2.7.7.1 
ITT  - Patients 
with Age ≥18 
years 
Summary, Change, and Percent Change from Baseline in Psoriasis 
Symptoms Diary (PSD) Individual Item Scores by Study Visit – Observed 
Data  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 60 of 63 
14.2.7.7.2 
ITT  - Patients 
with Age ≥18 
years 
Summary of Psoriasis Symptoms Diary (PSD) Individual Item Scores by 
Study Visit – Observed Data (ANCOVA)  
14.2.8.1 
ITT  
Summary, Change and Percent Change from Baseline in Scalpdex Total 
Score by Study Visit - Observed Data 
14.2.8.2 
ITT  
Summary of Scalpdex Total Score by Study Visit - Observed Data 
(ANCOVA)  
14.2.8.3 
ITT  
Scalpdex Individual Questionnaire Responses by Study Visit (Categorical) 
14.2.8.4 
ITT  
Scalpdex Individual Questionnaire Responses by Study Visit (Continuous) 
14.2.8.5.1 
ITT  
Summary, Change and Percent Change from Baseline in Scalpdex Score - 
Emotions Scale by Study Visit - Observed Data  
14.2.8.5.2 
ITT  
Summary of Scalpdex Score - Emotions Scale by Study Visit - Observed 
Data (ANCOVA)  
14.2.8.6.1 
ITT  
Summary, Change, and Percent Change from Baseline in Scalpdex Score - 
Symptoms Scale by Study Visit - Observed Data  
14.2.8.6.2 
ITT  
Summary of Scalpdex Score - Symptoms Scale by Study Visit - Observed 
Data (ANCOVA)  
14.2.8.7.1 
ITT  
Summary, Change, and Percent Change from Baseline in Scalpdex Score - 
Functioning Scale by Study Visit -Observed Data  
14.2.8.7.2 
ITT  
Summary of Scalpdex Score - Functioning Scale by Study Visit - Observed 
Data (ANCOVA)  
14.2.9.1 
 ITT  - Patients 
with Age ≥17 
years 
Summary, Change and Percent Change from Baseline in Dermatology Life 
Quality Index (DLQI) by Study Visit - Observed Data  
14.2.9.2 
 ITT  - Patients 
with Age ≥17 
years 
Summary of Dermatology Life Quality Index (DLQI) by Study Visit - 
Observed Data (ANCOVA)  
14.2.9.3 
ITT  - Patients 
with Age 12-16 
years 
Summary, Change and Percent Change from Baseline in Children’s 
Dermatology Life Quality Index (CDLQI) by Study Visit - Observed Data   
14.2.10.1 
ITT  
Summary, Change, and Percent Change from Baseline in Body Surface 
Area (%) by Study Visit - Observed Data  
14.2.10.2 
ITT  
Summary of Body Surface Area (%) by Study Visit - Observed Data 
(ANCOVA)  
14.2.11.1 
ITT  
Summary, Change, and Percent Change from Baseline in Extent of Scalp 
Involvement by Study Visit - Observed Data 
14.3 
Safety Summary 
14.3.1.1 
Safety  
Overall Summary of Treatment Emergent Adverse Events   
14.3.1.2 
Safety  
Treatment Emergent Adverse Events by System Organ Class and Preferred 
Term  
14.3.1.3 
Safety  
Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Maximum Severity  
14.3.1.4 
Safety  
Treatment Emergent Adverse Events by System Organ Class, Preferred 
Term, and Relationship to Study Drug  
14.3.1.5 
Safety  
Treatment Emergent Adverse Events by Preferred Term  
14.3.1.6 
Safety  
Treatment Emergent Serious Adverse Events by System Organ Class and 
Preferred Term  
14.3.1.7 
Safety  
Treatment Emergent Adverse Events Leading to Study Drug 
Discontinuation by System Organ Class and Preferred Term  
14.3.1.8 
Safety  
Treatment Emergent Adverse Events Leading to Study Discontinuation by 
System Organ Class and Preferred Term  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 61 of 63 
14.3.2.1 
Safety  
Quantitative Summary of Investigator Local Tolerability Assessment 
(Dermal Response) by Study Visit   
14.3.2.2 
Safety  
Categorical Summary of Investigator Local Tolerability Assessment 
(Dermal Response) by Study Visit   
14.3.2.3 
Safety  
Categorical Summary of Investigator Local Tolerability Assessment (Other 
Effects) by Study Visit   
14.3.2.4 
Safety  
Quantitative Summary of Subject Local Tolerability Assessment by Study 
Visit   
14.3.2.5 
Safety  
Categorical Summary of Subject Local Tolerability Assessment by Study 
Visit  Categorical Results  
14.3.3.1 
Safety  
Summary of Clinical Chemistry Laboratory Results (Standard Units) by 
Study Visit  
14.3.3.2 
Safety  
Shift from Baseline in Clinical Chemistry Laboratory Results (Standard 
Units) by Study Visit   
14.3.3.3 
Safety  
Summary of Hematology Laboratory Results (Standard Units) by Study 
Visit   
14.3.3.4 
Safety  
Shift from Baseline in Hematology Laboratory Results (Standard Units) by 
Study Visit   
14.3.3.5 
Safety  
Summary of Quantitative Urinalysis Laboratory Results (Standard Units) 
by Study Visit   
14.3.3.6 
Safety  
Shift from Baseline in Quantitative Urinalysis Laboratory Results 
(Standard Units) by Study Visit   
14.3.3.7 
Safety  
Summary of Qualitative Urinalysis Laboratory Results by Study Visit   
14.3.4.1 
Safety  
Summary of Vital Signs by Study Visit  
14.3.4.2 
Safety  
Change in Weight from Baseline by Study Visit   
14.3.4.3 
Safety  
Change in Weight from Baseline by Study Visit and Weight Loss 
Intentional/Non-Intentional Categories  
14.3.4.4 
Safety  
Shift from Baseline in BMI by Study Visit   
14.3.4.5 
Safety  
Shift from Baseline in BMI by Study Visit and Weight Loss 
Intentional/Non-Intentional Categories  
14.3.5  
Safety  
Shift from Baseline in Patient Health Questionnaire Depression Scale 
(PHQ-8)/Modified PHQ-Adolescents by Study Visit  
14.3.6  
Safety  
Summary of Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal 
Ideation and Suicidal Behavior by Study Visit  
14.3.7 
Safety  
Summary of Physical Examination by Study Visit  
14.3.8 
Safety  
Summary of Concomitant Medications by Anatomic Therapeutic Chemical 
(ATC) Class Level 4 and Preferred Term  
14.4 
Pharmacokinetic Data 
14.4.1 
PK  
Summary of Pharmacokinetic Concentration Results by Study Visit  
 
14.2. Planned Figure descriptions 
The following are planned summary figures for protocol ARQ-154-309. The figure numbers are 
place holders only and may be changed when figures are produced. 
 
Figure 
Number  
Populatio
n 
Figure Title/Summary 
14.2.1.11 
ITT  
Forest Plot of S-IGA Success at Week 8 - Multiple Imputation (Subgroup Analysis)  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 62 of 63 
14.2.1.12 
ITT  
Plot of Proportion (97.5 CI%) of Scalp Investigator Global Assessment (S-IGA) 
Success at Week 8 by Site - Observed Data (Supporting Analysis) ITT Population 
14.2.1.13 
ITT  
Plot of Proportion (97.5 CI%) of Scalp Investigator Global Assessment (S-IGA) 
Success at Week 8 - Multiple Imputation, Impact of Site (Supporting Analysis) 
14.2.2.11 
ITT  
Forest Plot of B-IGA Success at Week 8 - Multiple Imputation (Subgroup Analysis) 
ITT Population 
14.2.2.12 
ITT  
Plot of Proportion (97.5 CI%) of Body Investigator Global Assessment (B-IGA) 
Success at Week 8 by Site - Observed Data (Supporting Analysis) ITT Population 
14.2.2.13 
ITT  
Plot of Proportion (97.5 CI%) of Body Investigator Global Assessment (B-IGA) 
Success at Week 8 - Multiple Imputation, Impact of Site (Supporting Analysis) 
14.2.3.6 
ITT  
Plot of Mean (+/-SE) Change, and Percent Change from Baseline of Daily Scalp 
Itch-Numeric Rating Scale (SI-NRS) by Treatment Group over Time ITT Population 
14.3.1.9 
Safety  
Plot of Most Frequent (≥1.0%) Treatment Emergent Adverse Events by Preferred 
Term and Treatment Group  
 
 
 
 
 
14.3. Planned Listing Descriptions 
The following are planned data and patient/subject data listings for protocol number ARQ-154-309.  
 
In general, all listings will be sorted by site, and subject number. Screen failures will only be presented in listing 
16.1.1.  
 
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.  
 
Listing 
Number  
Population 
Listing Title/Summary 
16.2.1  
Screened 
Subjects 
Subject Disposition 
16.2.2.1 
ITT  
Protocol Deviations  
16.1.7  
ITT  
Randomization  
16.2.4.1 
ITT  
Demographics and Analysis Population 
16.2.4.2 
ITT  
Subject Baseline Characteristics  
16.2.4.3 
Safety  
Medical History 
16.2.5.1 
Safety  
Study Drug Application at the Study Site  
16.2.5.2  
PK  
Pharmacokinetic Blood Collection Dates and Times and Drug Concentrations 
16.2.6.1 
ITT  
Efficacy Endpoints  
16.2.6.2 
ITT  
Daily Scalp Itch and Worst Itch Numerical Rating Scale (SI-NRS and WI-NRS) 
16.2.7  
Safety  
Adverse Events 
16.2.8.1 
Safety  
Abnormal Clinical Laboratory Data: Clinical Chemistry  


 
Statistical Analysis Plan  
 
Sponsor Arcutis Biotherapeutics, Inc. 
 
Protocol Number ARQ-154-309  
 
PCN Number ARCU214118 
AD-ST-33.05  Effective date: 22-Jan-2018 
Version Final 2.0    |    11-Aug-2022    |    AD-PR-109.01  Effective date: 26-Jun-2017 
 Page 63 of 63 
16.2.8.2 
Safety  
Abnormal Clinical Laboratory Data: Hematology  
16.2.8.3 
Safety  
Abnormal Clinical Laboratory Data: Urinalysis 
16.2.9.1 
Safety  
Abnormal Vital Signs