A Randomized tRial Employing topiCal roflumilasT Foam to Treat Scalp Psoriasis (ARRECTOR)
Phase: PHASE3
Conditions: Scalp Psoriasis
Sponsor: Arcutis Biotherapeutics, Inc.



Protocol ARQ-154-309 
Arcutis Biotherapeutics, Inc. 
Amendment 3 
 
 
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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 
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No embarrassment 
As embarrassed as you  
can imagine 
 
  
 
 
 
 
 
 
 
 
 
© Novartis 2018 
 

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APPENDIX 7. SCALPDEX 
 

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APPENDIX 8. DERMATOLOGY LIFE QUALITY INDEX (DLQI) 
 

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APPENDIX 9. CHILDREN’S DERMATOLOGY LIFE QUALITY 
INDEX (CDLQI) 
 

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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 

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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. 

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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.