Clinical trial NCT04655313
Conditions: Psoriasis Plaque Psoriasis
Sponsor: Arcutis Biotherapeutics, Inc.
Start date: 2020-11-30; Completion date: 2022-01-12
Enrollment: 20 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 2, open label, maximal usage PK and safety study of ARQ-151 cream 0.3% in pediatric subjects (ages 6 to 11 years old) with plaque psoriasis:

Detailed description:

Arms: arm 1: Open label study of ARQ-151 cream 0.3% applied once daily for 4 weeks
Interventions: intervention 1: ARQ-151 cream 0.3%
Intervention descriptions: intervention 1: ARQ-151 cream 0.3% applied to chronic plaque psoriasis lesions once a day for 4 weeks

Protocol documents:
Prot_000.pdf: 




Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1  
 
22 Jan 2021 
Confidential 
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SUMMARY OF CHANGES 
The following sections have been changed in Amendment 1 of the ARQ-151-215 protocol: 
Section 
Summary of Changes 
Title Page  
Sponsor address, protocol version and date updated.  
1 Synopsis 
Synopsis updated throughout to reflect changes in the body of the 
protocol and summarized herein. The number of study sites was 
updated to reflect approximately 10 to 15 study sites planned. The 
planned countries were updated to include the Dominican 
Republic.  
1.1 Study Schema 
Schema updated to remove reference to serial PK collection.  
2  Schedule of Visits 
and Assessments  
Updated the visits and associated footnote for PK sampling to 
remove references to pre-dose PK collection at Baseline/Day 1, 
serial PK collection at Baseline/Day 1, and serial PK collection at 
Week 2.  
3 Abbreviations  
Removed references to abbreviations not included in the body of 
the protocol.  
6.1 Overall Study 
Design and Plan  
Edited to remove references to serial PK collection. Updated the 
definition of PK evaluable subjects in the maximal usage subset.  
6.5.1 Inclusion Criteria  
Updated inclusion criterion 6 to remove reference to serial PK 
collection.  
7.1.5  Laboratory Tests 
Clarified that if the Baseline visit is within 3 weeks of Screening, 
the Screening laboratory results will be used for Baseline.    
7.1.8  Adverse Events  
Clarified the timepoint when adverse events will be collected.  
7.3.2  Pharmacokinetics 
Sample Collection 
Edited to remove references to pre-dose and serial PK collection at 
Baseline/Day 1, and serial PK collection at Week 2.  The section 
title was updated.  
8.1.1 Pharmacokinetics 
Assessment 
Edited to remove duplicative description of PK collection 
timepoints.  
8.1.2 Pharmacokinetic 
Parameters 
Updated to remove reference to treatment groups.  
Appendix 6 COVID-19 
Study Site Guidance 
COVID-19 study site guidance added as an appendix. This 
guidance provides mitigation strategies to sites in the event 
subjects are unable to complete protocol-specific assessments 
onsite.  
Editorial changes made throughout to improve accuracy or readability 
 




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6.9.1 Drug Supplies, Packaging and Labeling .................................................................. 34 
6.9.2 Treatment Administration ........................................................................................ 34 
6.9.3 Treatment Compliance ............................................................................................. 36 
7 
STUDY PROCEDURES .................................................................................................... 36 
7.1 
Safety Assessments ................................................................................................. 36 
7.1.1 Screening.................................................................................................................. 36 
7.1.2 Physical Examination............................................................................................... 37 
7.1.3 Vital Signs, Height and Weight ............................................................................... 37 
7.1.4 12-lead ECGs ........................................................................................................... 38 
7.1.5 Laboratory Tests ...................................................................................................... 38 
7.1.6 Children’s Depression Inventory 2 .......................................................................... 39 
7.1.7 Local Tolerability Assessment ................................................................................. 39 
7.1.8 Adverse Events ........................................................................................................ 40 
7.2 
Efficacy Evaluations .............................................................................................. 41 
7.2.1 Investigator Global Assessment (IGA) and Intertriginous Investigator Global 
Assessment (I-IGA) ................................................................................................. 41 
7.2.2 Psoriasis Area and Severity Index (PASI) ............................................................... 42 
7.2.3 Worst Itch-Numerical Rating Scale (WI-NRS) ....................................................... 43 
7.2.4 Children’s Dermatology Life Quality Index (CDLQI) ............................................ 43 
7.2.5 Dermal Imaging ....................................................................................................... 43 
7.3 
Other Evaluations .................................................................................................. 44 
7.3.1 Body Surface Area (BSA) ....................................................................................... 44 
7.3.2 Pharmacokinetics Sample Collection ...................................................................... 44 
7.4 
Final Study Visit ..................................................................................................... 44 
7.5 
Early Termination Visit ........................................................................................ 45 
7.6 
Unscheduled Visit................................................................................................... 45 
7.7 
Adverse Events ....................................................................................................... 45 
7.7.1 Adverse Event Definition ........................................................................................ 45 
7.7.2 Serious Adverse Event ............................................................................................. 46 
7.7.3 Suspected Unexpected Serious Adverse Reaction (SUSAR) .................................. 47 
7.7.4 Safety Review with Subject ..................................................................................... 47 
7.7.5 Adverse Event Reporting ......................................................................................... 47 
7.8 
Reporting Pregnancy ............................................................................................. 49 
7.9 
Treatment Stopping Rules .................................................................................... 49 
8 
DATA ANALYSIS .............................................................................................................. 50 
8.1 
Statistical Methods ................................................................................................. 50 
8.1.1 Pharmacokinetics Assessment ................................................................................. 50 
8.1.2 Pharmacokinetic Parameters .................................................................................... 51 
8.1.3 Determination of Sample Size ................................................................................. 51 
8.1.4 Subjects to Analyze .................................................................................................. 51 
8.1.5 Interim Analysis ....................................................................................................... 51 


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8.1.6 Background and Demographic Characteristics ........................................................ 51 
8.1.7 Investigational Product Application Compliance .................................................... 51 
8.2 
Efficacy Evaluation ................................................................................................ 52 
8.2.1 Exploratory Endpoints ............................................................................................. 52 
8.3 
Safety Evaluation ................................................................................................... 52 
8.3.1 Adverse Events ........................................................................................................ 52 
8.3.2 Local Tolerance Assessment .................................................................................... 53 
8.3.3 Medical History and Physical Examinations ........................................................... 53 
8.3.4 Clinical Laboratory Results and Vital Signs ............................................................ 53 
8.3.5 Prior and Concomitant Medications ........................................................................ 53 
9 
STUDY ADMINISTRATION............................................................................................ 53 
9.1 
Ethics ....................................................................................................................... 53 
9.1.1 Ethics Review Board ................................................................................................ 53 
9.1.2 Ethical Conduct of the Study ................................................................................... 54 
9.1.3 Subject Information and Consent/Assent ................................................................. 54 
9.2 
Study Monitoring ................................................................................................... 54 
9.3 
Study Completion/Termination ............................................................................ 55 
9.3.1 Study Completion .................................................................................................... 55 
9.3.2 Study Termination ................................................................................................... 55 
9.4 
Data Quality Assurance ......................................................................................... 55 
9.5 
Data Handling and Record Keeping .................................................................... 55 
9.6 
Protocol Amendments and Deviations ................................................................. 56 
9.7 
Confidentiality and Privacy .................................................................................. 56 
9.8 
Conflict of Interest ................................................................................................. 57 
9.9 
Report Format ........................................................................................................ 57 
9.10 
Publication Policy................................................................................................... 57 
10 REFERENCES .................................................................................................................... 58 
11 APPENDICES ..................................................................................................................... 59 
 
 




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Amendment 1 
 
22 Jan 2021 
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1 
SYNOPSIS 
Protocol Title: 
An Open Label, 4-Week, Phase 2, Maximal Usage Pharmacokinetics 
and Safety Study of ARQ-151 Cream 0.3% Administered QD in 
Pediatric Subjects (ages 6 to 11 years old) with Plaque Psoriasis 
Investigational 
Product: 
ARQ-151 cream 0.3% 
IND: 
135681  
Clinical Indication: 
Plaque Psoriasis 
Study Objectives: 
• To evaluate the systemic exposure and characterize the plasma 
pharmacokinetic (PK) profile of ARQ-151 cream 0.3% and its 
major N-oxide metabolite, in pediatric subjects with plaque 
psoriasis involving body surface areas (BSA) of  at least 3%, 
under maximal usage conditions. 
• To evaluate the safety of ARQ-151 cream 0.3% applied QD to 
pediatric subjects with plaque psoriasis involving BSA of  at least 
2%.   
• To explore the efficacy of ARQ-151 cream 0.3% applied QD for 
4 weeks to pediatric subjects with plaque psoriasis involving BSA 
of at least 2%.    
Summary of Study 
Design: 
This is a phase 2, open label, maximal usage PK and safety study of 
ARQ-151 cream 0.3% in pediatric subjects (ages 6 to 11 years old) 
with plaque psoriasis: 
• At entry, subjects will have at least 2% BSA involvement 
(excluding the scalp, palms, soles), except for a subset of 
evaluable subjects who consent to a PK sample for maximal usage 
evaluation that will have at least 3% BSA involvement (excluding 
the scalp, palms, soles), and both groups of subjects will have a 
minimum IGA of Mild (‘2’).  
• Subjects who discontinue the study may be replaced.   
• Subjects/caregivers will apply ARQ-151 cream 0.3% QD for 
28 days to all affected areas of plaque psoriasis and any newly 
appearing plaque psoriasis lesions that arise during the study, 
except on the scalp.  
• Subjects/caregivers should maintain treatment of these areas with 
study drug for the duration of the study regardless of whether 
treatable areas of psoriasis clear prior to Week 4. 


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Amendment 1 
 
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Countries: 
Planned for the United States, Canada, and the Dominican Republic. 
Number of Sites: 
Approximately 10 to 15 sites planned  
Study Population: 
Approximately 20 male and female subjects ages 6 to 11 years old 
with plaque psoriasis: 
• All subjects must have at least 2% BSA psoriasis involvement at 
Baseline 
• However, a subset of 6 evaluable subjects who consent to a PK 
sample for maximal usage evaluation will have at least 3% BSA 
involvement (excluding the scalp, palms, soles) at Baseline 
o PK evaluable subjects (in the maximal usage subset) are 
defined as those that have PK results at Week 2. Unevaluable 
subjects may be replaced. 
• All subjects must have at least Mild (‘2’) psoriasis severity based 
on IGA at Baseline 
Main Inclusion 
Criteria: 
1. Informed consent of parent(s) or legal guardian, and, if age 
appropriate, assent by the subject, as required by local laws. 
2. Males or females, 6 to 11 years old (inclusive). 
3. Clinical diagnosis of psoriasis vulgaris of at least 2 months 
duration as determined by the Investigator or through subject 
interview.  Stable disease for the past 3 weeks. 
4. Psoriasis vulgaris on the face, extremities, trunk, and/or 
intertriginous areas involving at least 2% of BSA (excluding the 
scalp, palms, and soles). 
5. An Investigator Global Assessment of disease severity (IGA) of at 
least Mild (‘2’) at Baseline. 
6. Subject has adequate venous access for PK sampling in areas not 
involved by plaque psoriasis and not being treated with ARQ-151 
(e.g., back of the hands). 
7. 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). In addition, sexually active 
FOCBP must agree to use at least one form of highly effective 
contraception throughout the duration of the trial and for one 
week after application of the last dose. Highly effective forms of 
contraception include: oral/implant/ injectable/transdermal 
contraceptives, intrauterine device, and partner’s vasectomy. 
If barrier methods are used (e.g., condom with spermicide, 
diaphragm with spermicide), then 2 forms of contraception are 


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required in association with spermicide. The use of abstinence as 
a contraceptive measure is acceptable as long as this is a 
consistent part of a lifestyle choice and an acceptable backup 
method has been identified if the subject becomes sexually active. 
8. Females of non-childbearing potential must be pre-menarchal.  
9. In good health as judged by the Investigator, based on medical 
history, physical examination, 12-lead electrocardiogram (ECG), 
serum chemistry labs, hematology values, and urinalysis. 
10. Subjects and parent(s)/legal guardian(s) are considered reliable 
and capable of adhering to the Protocol and Visit Schedule, 
according to the judgment of the Investigator. 
Main Exclusion 
Criteria: 
1. Subjects with any serious medical or psychiatric condition or 
clinically significant laboratory, ECG, vital signs, or physical 
examination abnormality that would prevent study participation or 
place the subject at significant risk, as judged by the Investigator. 
2. Planned initiation or changes to concomitant medication that 
could, in the opinion of the Investigator, affect psoriasis vulgaris 
(e.g. beta blockers, ACE inhibitors).  
3. Current diagnosis of non-plaque form of psoriasis (e.g., guttate, 
erythrodermic/exfoliative, palmoplantar only involvement, or 
pustular psoriasis). Current diagnosis of drug-induced psoriasis. 
4. Subjects with any condition on the treatment area which, in the 
opinion of the Investigator, could confound efficacy 
measurements. 
5. Subjects who cannot discontinue the use of strong cytochrome 
P-450 CYP3A4 inducers (e.g., efavirenz, nevirapine, 
glucocorticoids, barbiturates (including phenobarbital), phenytoin, 
rifampin, and carbamazepine) for 2 weeks prior to Baseline/Day 1 
and during the study period. 
6. Subjects who cannot discontinue the use of strong cytochrome 
P-450 CYP3A4 inhibitors (e.g., indinavir, nelfinavir, ritonavir, 
clarithromycin, itraconazole, ketoconazole, nefazodone, 
saquinavir, suboxone and telithromycin) for 2 weeks prior to 
Baseline/Day 1 and during the study period.  
7. Subjects who are unwilling to refrain from prolonged sun 
exposure and from using a tanning bed or other artificial light 
emitting devices (LEDs) for 4 weeks prior to Baseline/Day 1 and 
during the study. 


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8. Subjects who cannot discontinue specific systemic therapies 
and/or topical therapies prior to the Baseline/Day 1 and during the 
study period according to Table 1. 
9. Current or a history of cancer within 5 years with the exception of 
fully treated skin basal cell carcinoma, cutaneous squamous cell 
carcinoma or carcinoma in situ of the cervix. 
10. Subjects with any infection requiring oral or intravenous 
administration of antibiotics, antifungal or antiviral agents within 
2 weeks prior to Baseline/Day 1. 
11. Known or suspected:  
a. severe renal insufficiency or moderate to severe hepatic 
disorders (Child-Pugh B or C) 
b. history of chronic infectious disease (e.g., hepatitis B, hepatitis 
C, or human immunodeficiency virus (HIV)) 
c. hypersensitivity to component(s) of the investigational 
products  
12. Subjects with a CDI-2 (parent report) raw score >20 at 
Screening/Baseline. 
13. Subjects with a history of a major surgery within 4 weeks prior to 
Baseline/Visit 1 or subjects who have a major surgery planned 
during the study. 
14. Subjects who are family members of the clinical study site, 
clinical study staff, or sponsor. 
15. Parent(s)/legal guardian(s) who are unable to communicate, read, 
or understand the local language.  Subjects who are unable to 
communicate or understand the local language, or who display 
another condition, which in the Investigator’s opinion, makes 
them unsuitable for clinical study participation. 
Duration of 
Participation for 
Subjects: 
All subjects will participate in screening (up to 3 weeks) and a 
Treatment phase (4 weeks). 
Upon completion of this study, participants may have the opportunity, 
subject to research site participation, to enroll in an open-label 
extension study of up to 24 weeks, receiving ARQ-151 cream 0.3% 
concentration (study ARQ-151-306).For subjects who enroll in 
ARQ-151-306, the Week 4 visit will complete this study.  Subjects 
who do not enroll in ARQ-151-306 will complete this study 
(ARQ-151-215) with the Week 5 Telephone Visit. 
Planned Dose Level: 
Subjects will receive ARQ-151 cream 0.3% QD x 28 days.   


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Amendment 1 
 
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Key Assessments: 
Safety will be monitored through local cutaneous tolerability 
assessments, vital signs, physical examination, safety labs 
(blood chemistries/hematology/urinalysis), ECGs, Children's 
Depression Inventory 2 (CDI-2, parent report), Children's 
Dermatology Life Quality Index (CDLQI), and reported Adverse 
Events (AEs). 
All AEs will be collected starting at Screening after the parent/legal 
guardian and, as appropriate, the subject has provided assent/informed 
consent. TEAEs should be recorded starting from the beginning of the 
treatment period.  
Efficacy assessments will include IGA, Intertriginous Area-IGA 
(I‑IGA), PASI, WI-NRS, BSA, and CDLQI. 
PK sample collection:  
• All enrolled subjects will have a trough PK sample at the Week 4 
visit.   
• A subset of 6 evaluable subjects who consent will have an 
additional PK sample collected pre-dose at the Week 2 visit.  
o PK evaluable subjects (in the maximal usage subset)  are 
defined as those that have PK results for Week 2. Unevaluable 
subjects may be replaced. 
Study Endpoints: 
 
• The primary endpoints will be PK, safety and tolerability.   
• Efficacy will be assessed as exploratory endpoints. 
Statistical 
Considerations: 
 
Safety 
The following analyses will be performed; however, no formal 
inferential statistics will be done on safety assessments. 
Descriptive statistics will be calculated for quantitative safety data and 
frequency counts will be compiled for classification of qualitative 
safety data.  All subjects who receive at least one confirmed dose of 
study drug will be included in the safety population.  
Adverse Events: 
A subject-by-subject treatment-emergent adverse event (TEAE) data 
listing, including verbatim term, preferred term, treatment, severity, 
and relationship to study drug, will be provided. 
The number of subjects experiencing adverse events (AEs) and 
number of AEs will be summarized by cohort using frequency counts. 
Medical History, Physical Examinations, Vital Signs, Safety Labs 
and ECGs: 


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Clinically significant physical examination parameters will be 
captured as adverse events.  
Vital signs and safety laboratory parameters will be summarized at 
each visit using descriptive statistics or frequencies and percentages, 
as appropriate. Changes from baseline in laboratory values and vital 
signs will also be summarized by visit. In addition, changes from 
baseline in weight and laboratory values will be summarized using 
shift tables. 
ECG data will be summarized with descriptive statistics. 
Efficacy 
All efficacy analyses will be exploratory. 
Descriptive statistics will be calculated for absolute and percentage 
change from baseline in IGA, I-IGA, PASI, WI-NRS, and BSA.  
The proportion of subjects with 50% and 75% improvement in PASI 
at post-baseline visits will also be described descriptively. 
Study Nuances: 
 
Non-medicated emollients, moisturizers and sunscreens will be 
allowed as normally used by the subjects, but may only be applied to 
non-treatment sites.  
PK Analysis: 
Pharmacokinetics Assessment  
Plasma levels of circulating roflumilast and its major N-oxide 
metabolite will be measured at the following time points: 
• All enrolled subjects will have a trough PK sample collected at 
the Week 4 visit.   
• A subset of 6 evaluable subjects who consent to a PK sample 
under maximal usage conditions will have an additional PK 
sample collected pre-dose at the Week 2 visit.  
Pharmacokinetic Parameters  
All subjects who are enrolled and receive at least one application of 
study drug will be included in the pharmacokinetic population. When 
possible, the exposure or roflumilast and its major N-oxide metabolite 
will be calculated based on plasma concentrations versus time profile 
data.   
 
 
 
 
 


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1.1 
Study Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
Baseline (Day 1) 
 
First Day of Treatment 
4 Week Treatment Period 
 
PK, Assessments, Clinic Visits  
An Open Label, 4-Week, Phase 2, Maximal Usage Pharmacokinetics and 
Safety Study of ARQ-151 Cream 0.3% Administered QD in Pediatric 
Subjects (ages 6 to 11 years old) with Plaque Psoriasis 
 
Approximately 20 male and female subjects ages 6 to 11 years old with 
plaque psoriasis will be treated with ARQ-151 cream 0.3%. At entry, subjects 
will have at least 2% BSA involvement (excluding the scalp, palms, soles), 
except for a subset of evaluable subjects who consent to a PK sample for 
maximal usage evaluation that will have at least 3% BSA involvement 
(excluding the scalp, palms, soles), and both groups of subjects will have a 
minimum IGA of Mild (‘2’). 
Not Participating in Open 
Label Extension Study 
 
End of Study 
 
Week 5 Phone Visit  
Participating in Open 
Label Extension Study 
 
ARQ-151-306 
 
Enrollment 


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2 
SCHEDULE OF VISITS AND ASSESSMENTS 
Study Procedure 
Screening 
Baseline 
Day 1 
Wk 2 
Day 14 
Wk 4 
Day 28/ET 
Wk 5 
Day 35  
Visit 
1 
2 
3 
4 
5 
Visit Window 
-3 weeks 
 
+/- 1 day 
+/- 3 days 
+/- 3 days 
Informed consent/assent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical and surgical history 
X 
 
 
 
 
Physical examinationa 
X 
X 
 
X 
 
I/E criteria 
X 
X 
 
 
 
Hematology, Serum Chemistries, and 
Urine Analysisb 
X 
X 
 
X 
 
Vital signs, weight, heightc 
X 
X 
X 
X 
 
IGA, I-IGA, PASI, BSA, WI-NRS, 
CDLQId 
X 
X 
X 
X 
 
Local cutaneous tolerability assessment 
(including Berger & Bowman and 
subject-rated stinging/burning)e 
 
X 
X 
X 
 
CDI-2  
X 
X 
X 
X 
 
Serum pregnancy testf  
X 
 
 
 
 
Urine pregnancy testf 
 
X 
 
X 
 
Resting 12-lead ECG 
X 
 
 
X 
 
PK samplingg 
 
 
X 
X 
 
Drug application and subject/family 
training in clinich 
 
X 
X 
 
 
Dispense investigational product kiti 
 
X 
X 
 
 
Weigh investigational product tubesj 
 
X 
X 
X 
 
Dispense/review diary 
 
X 
X 
X 
 
Adverse event assessmentk 
X 
X 
X 
X 
 
Concomitant medications 
X 
X 
X 
X 
 
Optional photographyl 
 
X 
X 
X 
 
Study Exitm 
 
 
 
 
X 
a Limited physical examination: skin, lungs, and heart only 
b To be collected at Screening, Baseline, and Week 4. If Baseline is within 3 weeks of Screening, the Screening 
results will be utilized.  
c Height will be measured at every visit (see Section 7.1.3 for the recommended procedure). Weight will be 
collected on every visit. Weight should be obtained using a calibrated weight scale and the same scale should be 
used for a subject throughout the duration of the study.  The subject should remove shoes and heavy clothing 
(sweaters or jackets), and empty pockets. The subject should stand with both feet in the center of the scale with 


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their arms at their side and hold still. Record the weight to the nearest decimal fraction (for example, 55.5 pounds 
or 25.1 kilograms). Measure the weight in triplicate and report the average weight in EDC. 
d BSA, IGA affected by plaque psoriasis will be determined to qualify for study entry (Screening and Baseline) 
and will be measured at the Week 2 and Week 4 visits.  Scalp, palms and soles should be excluded from 
consideration in these assessments.  Additionally, Intertriginous Area-IGA (I-IGA), PASI, and WI-NRS will be 
evaluated.  WI-NRS pruritus assessment will  be completed by subjects ≥ 8 years old, or by parent/caregiver for 
subjects < 8 years old. All other assessments will be performed by the Investigator or study staff, as appropriate.  
e Local tolerability assessments should be recorded prior to study drug application for the Investigator assessment 
of skin irritation (Berger and Bowman skin irritation score) and 10-15 minutes post-drug application for the 
subject’s ‘0-3’ burning/stinging assessment (subject-rating completed by the subject or parent/caregiver). At the 
Week 4 visit, only the Investigator assessment of skin irritation will be performed. Note for investigator 
tolerability assessments: reactions at the site of product IP application, which may occur post-Baseline, should be 
differentiated from the preexisting inflammation associated with the subject’s psoriasis. 
f For females that have started menstruation, a serum pregnancy test will be performed during Screening. A urine 
pregnancy test will be administered to all females of child-bearing potential. A negative result is required for 
continued participation in the study, and results must be available prior to dispensing of study drug  
g All enrolled subjects will have a trough PK sample collected at the Week 4 visit. A subset of 6 subjects who 
consent will provide an additional PK sample pre-dose (within 1 hour) at the Week 2 visit.  
h Subjects/caregiver to apply assigned IP in clinic at Baseline and Week 2. All Investigator assessments should be 
completed prior to IP application.  
I The number of kits to be dispensed is based on %BSA affected. See IP Handling Manual for details. Site should 
review IP kit to ensure sufficient IP is available until the next visit and only dispense additional IP if needed. 
j Every tube should be weighed and recorded when dispensed and returned.  
k Any emergent AEs will be followed in the clinic for up to 1 month at the Investigator’s discretion until resolved 
or otherwise judged as clinically stable. 
l Photography is planned to be performed at selected investigational sites.  Photography will be optional.  
All efforts will be made to de-identify the subjects. 
m Subjects who enroll into the open label extension study (ARQ-151-306) will complete the study at Week 4; 
subjects that do not enroll into ARQ-151-306 will complete the study with a Week 5 Telephone Follow-up. 
The Week 5 Telephone Follow-up is a call to the subjects to follow-up on any continuing adverse events related 
to the study drug. Telephone call also assesses any emergent adverse event post-Visit 4. Any emergent AEs will 
be followed in the clinic for up to 1 month at the Investigator’s discretion until resolved or otherwise judged as 
clinically stable. 
. 
 
 


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3 
ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse Event 
AMP 
Adenosine Monophosphate 
AD 
Atopic Dermatitis 
AUC 
Area Under the Curve 
BSA 
Body Surface Area 
Cmax 
Maximum Concentration 
cm 
Centimeter 
CDI 2 
Children’s Depression Inventory 2 
CDLQI 
Children's Dermatology Life Quality Index 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
ECG 
Electrocardiogram 
FDA 
U.S. Food and Drug Administration 
FOCBP 
Female of Child Bearing Potential 
GCP 
Good Clinical Practices 
GLP 
Good Laboratory Practices 
hr 
Hour 
IB 
Investigational Brochure 
IC50 
Half Maximal Inhibitory Concentration 
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation 
ID 
Identification  
IGA 
Investigator Global Assessment 
I-IGA 
Intertriginous Investigator Global Assessment  
IND 
Investigational New Drug 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
kg 
Kilogram 
LED 
Light Emitting Device 
µg 
Microgram 


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Abbreviation 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
min 
Minute 
mL 
Milliliter 
MUSE 
Maximal Use Systemic Exposure 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
ng 
Nanogram 
NOAEL 
No Observed Adverse Effect Level 
NSAID 
Nonsteroidal Anti-Inflammatory Drug 
P-450 
Cytochrome P450 
PASI 
Psoriasis Area and Severity Index  
PDE-4 
Phosphodiesterase 4 
PI 
Principal Investigator  
PK 
Pharmacokinetics 
QD 
Once Daily ("quaque die") 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TCPS 
Tri-Council Policy Statement 
TEAE 
Treatment Emergent Adverse Event 
Tmax 
Time to Reach Maximum Concentration 
TPA 
Target Plaque Area 
TPSS 
Target Plaque Severity Score 
US 
United States 
WI-NRS 
Worst Itch Numeric Rating Score 
 
 
 


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4 
BACKGROUND AND RATIONALE 
4.1 
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.  The pathogenesis of pediatric and adult 
psoriasis is believed to be similar.  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 past 15 years have witnessed a transformation in the systemic treatment of moderate to 
severe psoriasis with the advent of biological therapies.  However, for patients with milder forms 
of disease, best treated with topical options, the therapeutic landscape has not significantly 
changed in several decades.  Topical steroids come in all shapes and forms, but the lower 
potency steroids are not effective and the higher potency steroids are beset with issues of local 
skin atrophy and the potential for hypothalamic-pituitary axis suppression when applied over 
larger body surface areas and for prolonged periods of time.  Vitamin D has been the other staple 
of topical psoriasis treatment, but it is irritating, not suitable for use on the face or intertriginous 
areas, and its efficacy is rather modest.  Hence, there is substantial medical need for additional 
topical approaches in the treatment of psoriasis.  The study Sponsor is developing a topical 
cream formulation of roflumilast for the treatment of chronic plaque psoriasis.  Phase 2 results 
suggest that ARQ-151 may be a highly efficacious and well-tolerated topical treatment for 
psoriasis.  Accordingly, a phase 3 program is ongoing evaluating ARQ-151 cream 0.3% for the 
treatment of plaque psoriasis in subjects 2 years of age and older.  The present study is a 
maximal use pharmacokinetic trial with the to-be-marketed formulation.  The study is designed 
to ensure that the expected target patient population for ARQ-151 is properly represented, 
as well as to ensure that a suitable number of subjects with plaque psoriasis are evaluated and 
that PK is adequately characterized. 




















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6 
INVESTIGATIONAL PLAN 
6.1 
Overall Study Design and Plan 
This is a phase 2, open label, maximal usage PK and safety study of ARQ-151 cream 0.3% in 
pediatric subjects (ages 6 to 11 years old, inclusive) with plaque psoriasis.   
At entry, subjects will have at least 2% BSA involvement (excluding the scalp, palms, soles), 
except for a subset of evaluable subjects who consent to a PK sample for maximal usage 
evaluation that will have at least 3% BSA involvement (excluding the scalp, palms, soles), and 
both groups of subjects will have a minimum IGA of Mild (‘2’).  
Subjects who discontinue the study may be replaced.   
Subjects/caregivers will apply ARQ-151 cream 0.3% QD for 28 days to all plaque psoriasis 
affected areas and any newly appearing plaque psoriasis lesions that arise during the study, 
except on the scalp. 
Subjects/caregivers should maintain treatment of areas with study drug for the duration of the 
study regardless of whether treatable areas clear prior to Week 4. The palms and soles will be 
treated but will not be counted towards any measurements of efficacy (PASI, IGA, I-IGA, BSA). 
Approximately 20 male and female subjects ages 6 to 11 years old with plaque psoriasis: 
• All subjects must have at least 2% BSA psoriasis involvement at Baseline 
• However, a subset of 6 evaluable subjects who consent to a PK sample for maximal 
usage evaluation will have at least 3% BSA involvement at Baseline (excluding the scalp, 
palms, soles).  
o 
PK evaluable subjects (in the maximal usage subset) are defined as those that have 
PK results at Week 2. Unevaluable subjects may be replaced. 
• All subjects must have at least Mild (‘2’) psoriasis severity based on IGA at Baseline 
6.2 
Subject Participation 
All subjects will participate in screening (up to 3 weeks) and a Treatment phase (4 weeks). 
Upon completion of this study, participants may have the opportunity, subject to research site 
participation, to enroll in an open-label extension study of up to 24 weeks, receiving ARQ-151 
cream 0.3% concentration (study ARQ-151-306). 
• For subjects who enroll in ARQ-151-306, the Week 4 visit will complete this study 
(ARQ-151-215).  
• Subjects who do not enroll in ARQ-151-306 will complete this study (ARQ-151-215) 
with the Week 5 Telephone Visit. 


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6.3 
Numbering of Subjects 
All screened subjects will be identified by a unique six-digit subject ID number.  The first digit 
will be “5” while the next two digits correspond to the site number (assigned by the Sponsor, 
e.g., 01 to 05), the last three digits correspond to the sequential order in which the subject is 
screened for the study (e.g., Subject ID 505-001: first digit fixed at 5, Site 5 (next two digits), 
subject number 001 screened by that site [last three digits]).  
The clinical site is responsible for maintaining a current log of subject ID number assigned to 
that subject.  The subject ID number is required to be entered on all clinical study documentation 
(e.g., case report forms, labeling of clinical materials and sample containers, investigational 
product accountability logs, etc.).  
6.4 
Blinding 
This is an open label study, therefore the subjects, the Investigator and clinical personnel will be 
aware of the treatment an individual has received. 
6.5 
Selection of Study Population 
6.5.1 Inclusion Criteria 
Subjects must fulfill all of the following inclusion criteria to be eligible for participation in the 
study: 
1. Informed consent of parent(s) or legal guardian, and, if age appropriate, assent by the 
subject, as required by local laws. 
2. Males or females, 6 to 11 years old (inclusive). 
3. Clinical diagnosis of psoriasis vulgaris of at least 2 months duration as determined by the 
Investigator or through subject interview.  Stable disease for the past 3 weeks. 
4. Psoriasis vulgaris on the face, extremities, trunk, and/or intertriginous areas involving at 
least 2% of BSA (excluding the scalp, palms, and soles). 
5. An Investigator Global Assessment of disease severity (IGA) of at least Mild (‘2’) at 
Baseline. 
6. Subject has adequate venous access for PK sampling in areas not involved by plaque 
psoriasis and not being treated with ARQ-151 (e.g., back of the hands). 
7. 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). In addition, 
sexually active FOCBP must agree to use at least one form of highly effective 
contraception throughout the duration of the trial and for one week after application of 
the last dose. Highly effective forms of contraception include: oral/implant/ 
injectable/transdermal contraceptives, intrauterine device, and partner’s vasectomy. 
If barrier methods are used (e.g., condom with spermicide, diaphragm with spermicide), 
then 2 forms of contraception are required in association with spermicide. The use of 
abstinence as a contraceptive measure is acceptable as long as this is a consistent part of a 


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lifestyle choice and an acceptable backup method has been identified if the subject 
becomes sexually active. 
8. Females of non-childbearing potential must be pre-menarchal.  
9. In good health as judged by the Investigator, based on medical history, physical 
examination, 12-lead electrocardiogram (ECG), serum chemistry labs, hematology 
values, and urinalysis. 
10. Subjects and parent(s)/legal guardian(s) are considered reliable and capable of adhering 
to the Protocol and Visit Schedule, according to the judgment of the Investigator. 
6.5.2 Exclusion Criteria 
1. Subjects with any serious medical or psychiatric condition or clinically significant 
laboratory, ECG, vital signs, or physical examination abnormality that would prevent 
study participation or place the subject at significant risk, as judged by the Investigator. 
2. Planned initiation or changes to concomitant medication that could, in the opinion of the 
Investigator, affect psoriasis vulgaris (e.g. beta blockers, ACE inhibitors).  
3. Current diagnosis of non-plaque form of psoriasis (e.g., guttate, 
erythrodermic/exfoliative, palmoplantar only involvement, or pustular psoriasis). 
Current diagnosis of drug-induced psoriasis. 
4. Subjects with any condition on the treatment area which, in the opinion of the 
Investigator, could confound efficacy measurements. 
5. Subjects who cannot discontinue the use of strong cytochrome P-450 CYP3A4  inducers 
(e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), 
phenytoin, rifampin, and carbamazepine) for 2 weeks prior to Baseline/Day 1 and during 
the study period. 
6. Subjects who cannot discontinue the use of strong cytochrome P-450 CYP3A4 inhibitors 
(e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, 
nefazodone, saquinavir, suboxone and telithromycin) for 2 weeks prior to Baseline/Day 1 
and during the study period.  
7. Subjects who are unwilling to refrain from prolonged sun exposure and from using a 
tanning bed or other artificial light emitting devices (LEDs) for 4 weeks prior to 
Baseline/Day 1 and during the study. 
8. Subjects who cannot discontinue specific systemic therapies and/or topical therapies prior 
to the Baseline/Day 1 and during the study period according to Table 1. 
9. Current or a history of cancer within 5 years with the exception of fully treated skin basal 
cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix. 
10. Subjects with any infection requiring oral or intravenous administration of antibiotics, 
antifungal or antiviral agents within 2 weeks prior to Baseline/Day 1. 
11. Known or suspected:  


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a. 
severe renal insufficiency or moderate to severe hepatic disorders (Child-Pugh B or 
C) 
b. 
history of chronic infectious disease (e.g., hepatitis B, hepatitis C, or human 
immunodeficiency virus (HIV)) 
c. 
hypersensitivity to component(s) of the investigational products 
12. Subjects with a CDI-2 (parent report) raw score >20 at Screening/Baseline 
13. Subjects with a history of a major surgery within 4 weeks prior to Baseline/Visit 1 or 
subjects who have a major surgery planned during the study. 
14. Subjects who are family members of the clinical study site, clinical study staff, 
or sponsor. 
15. Parent(s)/legal guardian(s) who are unable to communicate, read, or understand the local 
language.  Subjects who are unable to communicate or understand the local language, 
or who display another condition, which in the Investigator’s opinion, makes them 
unsuitable for clinical study participation. 
6.6 
Removal of Subjects from the Study 
Subject participation in this trial may be discontinued for any of the following reasons: 
1. 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 of the Protocol. 
2. Occurrence of a treatment-emergent adverse event (TEAE) or considerable worsening of 
an AE 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 
stabilizes. 
3. Pregnancy 
4. Subject's decision to withdraw from the study. 
5. Weight loss of >5% if not dieting and after consultation with the Sponsor, at the 
Investigator’s discretion. 
6. CDI-2 raw total score of 34, after consultation with a mental health professional, 
the Sponsor, and at the Investigator’s discretion. 
7. Requirement for use of prohibited concomitant medication after consultation with the 
Sponsor and Medical Monitor. 
8. Subject’s repeated failure to comply with protocol requirements or study related 
procedures. 
9. The subject interrupts trial study drug application for more than 50% of scheduled doses. 
10. Termination of the study by the Sponsor, FDA, or other regulatory authorities. 


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6.7 
Replacement of Subjects that Withdraw or are Discontinued from the Study 
Subjects that withdraw or are discontinued from the study prior to the Week 4 Visit, may be 
replaced.  
6.8 
Prohibitions and Concomitant Therapy 
Prohibited medications and products are detailed in Table 1. (Excluded Medications and 
Treatments).  
Table 1. 
Excluded Medications and Treatments 
Excluded Medications and Treatments 
Washout Period Prior to 
Baseline 
Systemic treatment with biological therapies with a possible effect on psoriasis vulgaris within the following 
time periods prior to Baseline/Day1 
Etanercept 
4 weeks 
Adalimumab, infliximab 
8 weeks 
All other Biologics  
12 weeks or 5 half-lives, 
whichever is longer 
All other therapies with a possible effect on psoriasis vulgaris 
Oral/systemic corticosteroids, retinoids, apremilast, methotrexate, cyclosporine 
and other systemic immunosuppressants 
4 weeks 
PUVA or NBUVB phototherapy 
4 weeks 
Sedating antihistamines 
1 week 
Topical anti-psoriasis medications (e.g., topical corticosteroids, vitamin D 
analogs, prescription shampoos) (except for emollients) 
1 week 
Strong cytochrome P-450 CYP3A4 inhibitors e.g., indinavir, nelfinavir, ritonavir, 
clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, suboxone and 
telithromycin 
2 weeks 
Strong cytochrome P-450 CYP3A4 inducers e.g., efavirenz, nevirapine, 
glucocorticoids, barbiturates (including phenobarbital), phenytoin, rifampin, and 
carbamazepine 
2 weeks 
Tanning beds, other light emitting devices 
4 weeks  
Investigational drugs 
30 days or 5 half-lives, 
whichever is longer 
Note:  Eye and ear 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. 
Non-medicated emollients, moisturizers and sunscreens will be allowed as used normally by the subjects. These 
can be applied only to non-treated areas as needed and should not be used within 12 hours of a study visit. 
A tar-containing or dandruff shampoo (zinc pyrithione or selenium sulfide) is allowed for treatment of the scalp. 
Concomitant other medications for chronic conditions (eg, NSAIDs, statins, anti-hypertensives) are permitted 
unless specifically prohibited in the Protocol. 


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Generally, the addition of new medications, including nonprescription medications, during the 
course of the study is discouraged.  However, the short-term use of a medication may be 
authorized by the Investigator.  The Investigator must make the decision to authorize the use of 
any such a medication only after consideration of the clinical situation, the potential for masking 
symptoms of a more significant underlying event, and whether the use of the medication will 
compromise the outcome or validity of the clinical investigation.  If medication is required, 
the name, strength, frequency, duration of use, and reason for use will be recorded in source 
documents and entered into the 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 ‘Exclusions’ (Table 1).  
6.9 
Treatment 
6.9.1 Drug Supplies, Packaging and Labeling 
ARQ-151 cream 0.3% will be in 45 gram (weight of cream) squeeze tubes. The tubes will be 
packaged in kits, containing multiple tubes of investigational product. The number of kits 
dispensed to a subject will be based on the BSA involvement of plaque psoriasis. The kits will be 
labeled in an open-label manner. The kit(s) dispensed to a subject will be labeled with a unique 
number. 
The Sponsor will supply sufficient quantities of the investigational product to each site to allow 
for completion of this study. 
Records will be made of the receipt and dispensing of the investigational products supplied.  
At the conclusion of the study, any unused investigational products will be returned to the 
Sponsor or designee, or destroyed, as per Sponsor instructions. 
Refer to the current version of the IP Handling Manual for details on the accountability, storage, 
and management of the IP. 
6.9.2 Treatment Administration 
ARQ-151 cream 0.3% is administered once daily as a topical product to cover the skin surface at 
an application rate of approximately 2 mg/cm2. Each site and each subject will be provided a 
digital scale to accurately measure the proper amount of cream to be applied to the psoriatic 
lesions. Each site will be provided a calculation program that uses the subject’s height, weight, 
and %BSA of plaque psoriasis involvement to calculate the correct amount of ARQ-151 to be 
applied once a day to the psoriatic lesions. 
At the Baseline visit, the Investigator will calculate daily IP to be applied in grams using the 
calculation tool.  
• IP tubes will be weighed prior to and immediately after IP application (Cap On)  
• IP will be weighed into a plastic dish using the digital scale  


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Investigator will confirm calculated IP adequately covers the entire involved area of plaque 
psoriasis. The Investigator can adjust IP usage up or down based on their clinical judgement or 
may consider the calculated expected IP weight as acceptable. The plastic dish should be 
reweighed after IP application to determine the actual amount of IP used.  
At the Baseline visit, the study staff will demonstrate to the subject and/or parent/caregiver how 
to use the digital scale to measure the proper amount of ARQ-151 cream to apply. ARQ-151 
cream is applied to psoriasis lesions as a thin film and rubbed in using the index and middle 
finger, thoroughly but gently, until the ‘white’ has disappeared. The subject or parent/caregiver 
will then apply the weighed amount of ARQ-151 to the psoriasis lesions once a day.  
If a parent/guardian/caregiver helps apply the study medication, they should wash their hands 
with soap and water when finished.   
For days that are a clinic visit, the IP will be applied in the clinic and the subject does not apply 
any further IP that day. All psoriasis lesions should be treated using the IP amount as noted in the 
Subject Body Diagram (see Appendix 1), except for the scalp.  
Re-training will be conducted at subsequent visits as needed (i.e., if the returned tube(s) weighs 
substantially different than the expected weight). 
Note: 
• All subjects should apply medication each evening (except on clinic visit days) at least 
15 minutes after showering or bathing (if they take an evening shower/bath) and then not 
wash areas where ARQ-151 cream has been applied until at least 4 hours after study drug 
application and preferably not until the following morning. Investigational product 
should be applied at least 20 minutes before going to bed. 
• Subjects should maintain treatment of areas with study drug for the duration of the study 
regardless of whether treatable areas of psoriasis clear prior to Week 4 visit. 
New lesions that develop during the study should be treated (except scalp). An unscheduled visit 
is not required for starting treatment of new lesions. 
Each investigational product tube will be weighed prior to dispensing at the Baseline visit and at 
subsequent visits. Investigational product tubes must be returned by subjects at each study visit, 
both empty and full, and will be weighed. If the subject’s actual use is substantially different than 
the expected use for the subject’s BSA, the subject/parent/caregiver will be retrained on the 
study drug application technique.  
At the final clinic visit, the subject should return all IP (used or unused), the digital scale, 
and any remaining plastic dishes. 
Refer to the Investigational Product (IP) Handling Plan for detailed instructions. 


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6.9.3 Treatment Compliance  
Investigational product tubes will be weighed at each clinic visit. 
Subjects/caregivers 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.  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 Case Report Forms (CRFs). If a subject misses a dose, they should be 
instructed to return to the protocol investigational product administration schedule (i.e. if subject 
forgets a dose they should wait until 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 study drug application period and does not miss 
more than 3 consecutive doses. 
Compliance will be assessed by review of the dosing diary. Weight of investigational product 
applied (via dispensed and returned tube weights) will be measured for reporting purposes. 
If the diary shows less than 80% of expected use, the subject is using too little study drug and 
retraining must be conducted and documented. 
Compliance will be documented in source and in eCRF. 
7 
STUDY PROCEDURES 
The Schedule of Visits and Assessments (Section 2) summarizes the clinical procedures to be 
performed at each visit. Individual clinical procedures are described in detail below. Additional 
evaluations/testing may be deemed necessary by the PI and/or the Sponsor for reasons related to 
subject safety. 
7.1 
Safety Assessments 
This study assesses the safety, efficacy, and pharmacokinetics of ARQ-151 cream. Safety will be 
determined by evaluating physical examinations, 12-lead ECGs, local tolerability assessments, 
vital signs/weight, clinical laboratory parameters, Children's Depression Inventory 2 
(CDI-2, parent report), and AEs as outlined in the Schedule of Visits and Assessments  
(Section 2). If deemed necessary, additional safety assessments will be performed at the 
discretion of the Investigator. 
7.1.1 Screening 
Within 3 weeks prior to the first dosing, subjects/legal guardians will be provided details of study 
requirements and sign an informed consent form and, when applicable, assent form.  Medical 
history and demographic data including sex, age, race, ethnicity, body weight (kg), and 
height (cm) will be recorded. Each subject will undergo plaque psoriasis assessments, a physical 
examination, ECG, vital sign measurements (blood pressure, heart rate, and temperature) and 
laboratory tests: hematology, chemistry, urinalysis and a pregnancy test for female subjects of 


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child bearing potential. Abnormal or questionable serum chemistry tests may be repeated at the 
discretion of the Investigator. 
All screened subjects will receive a screening number and be entered into the study tracking 
document. 
7.1.2 Physical Examination 
Physical examinations will be performed as follows: 
• 
Screening, Baseline, and Week 4.   
The physical exam will be limited to skin, lungs and heart only. 
7.1.3 Vital Signs, Height and Weight 
Vital signs will be collected (in seated position after 5 mins) at timepoints noted below: 
• Weight, height, blood pressure, heart rate, and temperature will be measured at 
Screening, Baseline, Week 2, and Week 4. 
o 
For both weight and height measurements, the investigator or examiner should be 
trained in measuring height and weight as well as in calibration procedures  
o 
Ideally, the same person should measure the subject at every visit 
o 
Attempts should be made to schedule visits, so that measurements can be taken at 
approximately the same time throughout the study  
o 
The parent / caregiver may help with the measurements and to soothe and comfort 
the child, as needed  
o 
Explain to the parent/ caregiver the steps in the procedures and that it is important 
to keep the child still and calm to obtain good measurements, as needed  
o 
For measuring weight, use a calibrated scale with appropriate range and resolution, 
and the same scale should be used for a subject throughout the duration of the study 
 
Subjects must remove shoes, bulky layers of clothing, and jackets so that only 
light clothing remains 
 
Subjects must also remove the contents of their pockets and remain still 
during measurement of weight 
 
Have the child or teen stand with both feet in the center of the scale with their 
arms at their side and hold still  
 
Record the weight to the nearest decimal fraction (for example, 55.5 pounds 
or 25.1 kilograms)  


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o 
For measuring length, a device such as a stadiometer should be used and placed on 
a flat, stable surface 
 
Remove the child or teen’s shoes, bulky clothing, and hair ornaments, and 
unbraid hair that interferes with the measurement 
 
Lower the headpiece until it firmly touches the crown of the head.  
 
Accurately record the height to the nearest 1/8th inch or 0.1 centimeter  
o 
For both weight and height, three reproducible measurements of both the child’s 
weight and height should be recorded and the average of the 3 recordings will be 
entered onto the eCRF 
7.1.4 12-lead ECGs 
12-lead ECGs will be performed as follows: 
• Screening and Week 4. 
ECGs will be performed on subjects after 5 minutes in the supine position. All ECG tracings and 
readouts will be reviewed by the central reader at the ECG laboratory. 
7.1.5 Laboratory Tests 
All tests listed below will be performed as follows: 
• Screening, Baseline (see also Section 2, Schedule of Visits and Assessments footnote 
“b”) and Week 4. If the Baseline visit is within 3 weeks of the Screening, the Screening 
laboratory results will be used for Baseline.    
All tests listed below will be performed according to the Study Events Flow Chart unless 
otherwise noted. The collection of specimens will be in a non-fasting state (no food restrictions). 
In addition, laboratory safety tests may be performed at various unscheduled time points, 
if deemed necessary by the Investigator. 
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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Urinalysis 
 
Additional Tests 
• 
pH 
• 
Specific gravity 
• 
Protein* 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Blood* 
• 
Nitrite* 
• 
Urobilinogen 
• 
Leukocyte esterase* 
 
• 
Urine pregnancy test** 
(for females of child bearing potential only) 
• 
Serum pregnancy test (hCG)*** 
 
 
* 
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. 
** At baseline and Week 4 for FOCBP only 
*** At screening only and only for FOCBP that have started menstruation 
7.1.6 Children’s Depression Inventory 2 
The CDI-2 Assessment will be performed as follows: 
• Screening, Baseline, Week 2, and Week 4 
The CDI-2 quantifies depressive symptomatology and is recommended for use in initial 
evaluation and is appropriate when there is a need for an assessment and robust description of a 
child’s depressive symptoms. 
This study will use the CDI Parent Report Form. An example of the Parent report form is 
presented in Appendix 2. 
7.1.7 Local Tolerability Assessment  
Investigator Local Tolerability Assessment will be performed as follows: 
• Baseline, Week 2, and Week 4 
Application site reactions will be graded at the timepoints outlined in the Schedule of Visits and 
Assessments (Section 2). Irritation reactions are graded using the scale detailed in the following 
section (Berger 1982). Reactions at the site of product application, which may occur 
post-Baseline, should be differentiated from the preexisting inflammation associated with the 
subject’s plaque psoriasis. 
The investigator assessments will be conducted by the investigator prior to study drug 
application in the clinic. 


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Dermal Response 
0 = no evidence of irritation 
1 = minimal erythema, barely perceptible 
2 = definite erythema, readily visible; minimal edema or minimal papular response 
3 = erythema and papules 
4 = definite edema 
5 = erythema, edema and papules 
6 = vesicular eruption 
7 = strong reaction spreading beyond application site 
Other Effects 
 
A = slight glazed appearance 
 
B = marked glazing 
 
C = glazing with peeling and cracking 
 
D = glazing with fissures 
 
E = film of dried serous exudates  
 
F = small petechial erosions and/or scabs 
G = no other effects 
 
Subject Local Tolerability Assessment will be performed as follows: 
• Baseline, Week 2 
This assessment will be administered by the site 10 to 15 minutes after study drug application in 
the clinic at Baseline and at Week 2.  Response may be by the subject and/or parent/caregiver, 
as deemed appropriate by the Investigator. 
Grade 
Sensation Following Drug Application 
0 (none) 
No sensation 
1 (mild) 
Slight warm, tingling sensation; not really bothersome 
2 (moderate) 
Definite warm, tingling sensation that is somewhat bothersome 
3 (severe) 
Hot, tingling/stinging sensation that has caused definite discomfort 
7.1.8 Adverse Events  
Adverse events (AEs) will be collected starting at Screening after the parent/ legal guardian and, 
as appropriate, the subject has provided assent/informed consent. TEAEs should be recorded 
starting from the beginning of the treatment period. 
Any treatment emergent AEs will be followed in the clinic for up to one month at the 
Investigator’s discretion until resolved or otherwise judged as clinically stable. 
For further details on Adverse Events please see Section 7.7. 




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I-IGA 
For subjects with intertriginous area involvement of at least ‘mild’ severity by IGA (I-IGA≥2) at 
Baseline (using the IGA scale shown above but evaluating intertriginous areas ONLY and NOT 
whole body involvement), an IGA for the intertriginous region alone (I-IGA) will be recorded at 
Screening, Baseline, Week 2, and Week 4. 
This ‘intertriginous area IGA’ (I-IGA) should be done AFTER the ‘standard whole body 
IGA’ in subjects who qualify. 
7.2.2 Psoriasis Area and Severity Index (PASI) 
Assessments will be performed as single assessments from which PASIs will be calculated. 
PASI assessment will be performed at Screening, Baseline/Day 1, Week 2, and Week 4 visits.  
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 (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/mPASI. 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 
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 


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7.2.3 Worst Itch-Numerical Rating Scale (WI-NRS) 
WI-NRS Assessments will be performed as follows: 
• Screening, Baseline, Week 2, and Week 4 
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”). WI-NRS pruritus 
assessment will be completed by subjects ≥ 8 years old, or by parent/caregiver for subjects 
< 8 years old.    
 
7.2.4 
Children’s Dermatology Life Quality Index (CDLQI) 
CDLQI (age 2-16 years) will be completed as follows: 
• Screening, Baseline, Week 2, and Week 4 
The Children's Dermatology Life Quality Index (CDLQI) allows a simple, compact and uniform 
assessment of patients with skin diseases in general, in which higher scores indicate poorer 
disease-related quality of life. Subjects/caregivers will complete the CDLQI. See Appendix 4 for 
the CDLQI. 
7.2.5 
Dermal Imaging 
Medical photography will be performed at participating sites on consenting/assenting subjects as 
follows: 
• Baseline, Week 2, and Week 4 
Photography should be focused on single lesions or specific body sections (e.g. arm). Subjects 
with intertriginous involvement also will have photographs taken of the intertriginous area.  
Body or half-body photographs should only be taken if necessary. All efforts will be made to 
de-identify the subjects. Subjects who are unwilling to participate in the medical photography 
will be allowed to opt out of this procedure and document on the informed consent form.  
Refer to the current Photography Manual for instructions regarding photography. 


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7.3 
Other Evaluations 
7.3.1 Body Surface Area (BSA) 
BSA Assessments will be performed as follows: 
• Screening, Baseline, Week 2, and Week 4 
The BSA affected by plaque 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 
(BSA).   
Note: All plaque psoriasis lesions on a subject will be treated including the face, trunk, 
genitals/skin folds, or limbs (excluding the scalp). The palms and soles will be treated but will 
not be counted towards any measurements of efficacy (PASI, IGA, BSA). 
Body Diagram 
The body diagram (see Appendix 1) will be completed as follows: 
• Baseline 
A copy of the body diagram will be provided to the subject for study drug application at home.  
7.3.2 Pharmacokinetics Sample Collection 
Plasma levels of circulating roflumilast and its major N-oxide metabolite will be measured at the 
following time points: 
• All enrolled subjects will have a trough PK sample at the Week 4 visit.   
• A subset of 6 subjects who consent will have an additional PK sample collected pre-dose at 
the Week 2 visit.   
Ensure investigational product is not applied in the area where PK will be drawn. 
A manual for blood sampling, collection, processing, and sample shipment will be provided in a 
separate document. 
7.4 
Final Study Visit 
The approximate final study visit will occur at Week 4 for those subjects that enroll into the 
Open Label Extension study (ARQ-151-306), or Week 5 (Day 35 – Telephone Follow-up) for 
those subjects that do not enroll in ARQ-151-306. See Schedule of Visits and Assessments 
(Section 2).  


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7.5 
Early Termination Visit 
If a subject is withdrawn or wishes to exit the study, a termination visit will be scheduled. 
This visit should include the procedures and assessments that would be performed at the Week 4 
visit (Day 28). 
7.6 
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 
The following information also will be collected: 
• IGA/I-IGA and PASI 
• BSA affected with plaque psoriasis  
• Local tolerability assessment (by Investigator) 
The rules for how to tally IGA/I-IGA, BSA or other proportions of categorical responses will be 
described in the Statistical Analysis Plan. 
7.7 
Adverse Events 
7.7.1 Adverse Event Definition 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.  
AEs will be collected following informed consent of the subject until one month after treatment.  
A treatment emergent adverse event (TEAE) is defined as an AE that started post application of 
investigational product at the Baseline visit or was present at treatment initiation but worsened 
during treatment, through study completion.  
Application site reactions will be considered adverse events if they require intervention, 
suspension or discontinuation of study drug.  


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7.7.2 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.  If any AEs are serious, as defined by ICH Guidelines 
for Clinical Safety, required procedures will be followed.  All SAEs will be reported to the 
Sponsor via fax or e-mail within 24 hours of becoming aware of the event, whether or not the 
serious events are deemed drug-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 IRB will be notified of the Alert 
Reports as per FDA, ICH and the IRB’s policies and procedures. 
An SAE is any AE that in the view of either the PI or Sponsor, results in any of the following 
outcomes: Death, a life-threatening AE, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect.  Important medical events 
that may not result in death, be life-threatening, or require hospitalization may be considered 
serious when, based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical or surgical intervention to prevent one of the outcomes listed in the above 
definition. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.  
Life-threatening is defined as an AE that in the view of the PI or Sponsor, places the subject at 
immediate risk of death. It does not include an AE that, had it occurred in a more severe form, 
might have caused death. 
Hospitalization does not include the following: 
• Rehabilitation facilities, hospice facilities or respite care (e.g. caregiver relief) 
• Nursing homes or skilled nursing facilities 
• Emergency room visits 
• Same day surgeries (as outpatient/same day/ambulatory procedures) 
• <24 hour admissions for observation or evaluation 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical AE is 
not in itself an SAE.  Examples include: 
• Admission for treatment of a preexisting condition that did not worsen 
• Hospitalizations for cosmetic elective surgery, social, and/or convenience admissions 
• Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the individual subject. 


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• Diagnostic and therapeutic procedures, such as surgery, should not be reported as AEs; 
however, the medical condition for which the procedure was performed should be 
reported if it occurs during the reporting period and meets the definition of an AE.  
For example, an acute appendicitis that begins during the AE reporting period should be 
reported as an AE, and the resulting appendectomy should be recorded as treatment of the 
AE. 
Unexpected is defined as an AE that is not listed in the IB or is not listed at the specificity or 
severity that has been observed; or is not consistent with the risk information described in the 
general investigational plan or elsewhere in the IND. 
If a SAE occurs to a subject on this study, contact the Sponsor personnel listed in Key Contacts 
List (provided separately) within one business day of knowledge of event.  
7.7.3 Suspected Unexpected Serious Adverse Reaction (SUSAR)  
This is defined as a serious adverse reaction, the nature or severity of which is not consistent 
with the known study treatment information. A serious event or reaction is not defined as a 
SUSAR when: ‘it is serious but expected’ or it does not fit the definition of an SAE, whether 
expected or not.  
7.7.4 Safety Review with Subject 
At each follow-up visit, subjects and/or caregivers will be queried with an open-ended question 
such as: ‘How have you been feeling since your last visit?’  Additionally, the study staff will 
review subject diaries and, if it appears that a potential AE was recorded, study staff will query 
the subject and determine if an AE occurred.   
AEs (whether serious or non-serious) and clinically significant abnormal laboratory test value(s) 
will be evaluated by the PI and treated and/or followed up for up to one month after end of 
treatment until the symptoms or value(s) return to normal, or acceptable levels, as judged by the 
PI. 
Where appropriate, medical test(s) and/or examination(s) will be performed to document 
resolution of event(s). Outcome may be classified as resolved, improved, unchanged, worse, 
fatal or unknown (lost to follow-up). 
7.7.5 Adverse Event Reporting 
The PI will review each event and assess its relationship to drug treatment (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 (resolved, improved, 
unchanged, worse, fatal, or unknown/lost to follow-up) of each event will be noted. 
• The relationship of each AE to the study drug will be assessed using the following 
definitions: 


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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. 
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. 


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AEs will be coded using the most current MedDRA® version available at the start of the study. 
7.8 
Reporting Pregnancy 
During the study, all subjects should be instructed to contact the investigator immediately if they 
suspect they might be pregnant (e.g., missed or late menstrual period).  If pregnancy is 
confirmed, the subject will be withdrawn from the study and followed until the pregnancy comes 
to term. 
The investigator is responsible for reporting all available pregnancy information on the 
pregnancy report within 24 hours of becoming aware of the event, although pregnancy itself is 
not considered an AE.  Study treatment must be discontinued immediately in the event of a 
pregnancy.  The subject should be referred to an obstetrician/gynecologist experienced in 
reproductive toxicity for further evaluation and counseling. Monitoring of the subject should 
continue until the conclusion of the pregnancy.  Follow-up information detailing the outcome of 
the pregnancy and the health of the newborn should be reported as it becomes available. 
Should the pregnancy result in a congenital abnormality or birth defect, a SAE report must be 
submitted.  Furthermore, all neonatal deaths that occur within 30 days of the birth should be 
reported as SAEs, without regard to causality.  In addition, any infant death that occurs after the 
30-day reporting period that the investigator suspects are related to the in-utero exposure to the 
study treatment should also be reported. 
7.9 
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 study drug, 
the Investigator should immediately contact the Medical Monitor to discuss if the subject should 
be discontinued from the study. 
Treatment for any individual subject will be discontinued if the subject:  
• Experiences a serious adverse event (SAE) or a clinically significant non-serious AE 
which in the opinion of the Principal Investigator or Medical Monitor warrants 
discontinuation from the study for that subject’s well-being. 
• A severe (Grade 3) laboratory abnormality (confirmed by repeat sample and considered 
related to study drug; see Appendix 5).  
Dosing of study drug for an individual subject may be suspended for safety concerns other than 
those described above, at the discretion of the investigator if he/she feels the subject’s safety may 
be threatened. 
CDI-2 raw total score of 34 should be referred promptly to a mental health care professional and 
consideration be given to discontinuation from study drug.   
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 study drug. 


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As noted above, study treatment must be discontinued immediately in the event of a female 
subject’s pregnancy.   
Treatment should be interrupted: 
• If a subject develops an application site reaction with the clinical appearance of an 
‘irritation reaction’, and with a severity of a Dermal Response Score of 5 (erythema, 
edema and papules) or greater on the scale of Berger and Bowman, treatment should be 
interrupted for up to one week and may then be resumed if the reaction has, in the 
opinion of the Investigator, adequately resolved.   
Treatment should be discontinued: 
• If the reaction reoccurs, treatment 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. 
8 
DATA ANALYSIS 
Data will be handled and processed according to the Contract Research Organization’s Standard 
Operating Procedures, which are written based on the principles of GCP. 
8.1 
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.  Any changes to the methods described in the final SAP will be described and justified 
in the clinical study report.  
All statistical processing will be performed using SAS® (Version 9.4) unless otherwise stated. 
No interim efficacy analyses are planned. 
Descriptive statistics will be used to provide an overview of the safety, efficacy, and 
pharmacokinetic results.  For categorical parameters, the number and percentage of subjects in 
each category will be presented. The denominator for percentage will be based on the number of 
subjects appropriate for the purpose of analysis.  For continuous parameters, descriptive statistics 
will include n (number of subjects), mean, standard deviation (SD), median, minimum, 
and maximum. No formal inferential statistics will be performed for this open-label study. 
8.1.1 Pharmacokinetics Assessment 
For all subjects, blood samples for the determination of roflumilast and its N-oxide metabolite 
will be collected at scheduled time points as delineated in the Schedule of Visits and 
Assessments (Section 2). Plasma drug concentrations at each time point will be summarized 
using descriptive statistics, reporting n, mean, standard deviation, median, minimum, and 
maximum. 


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8.1.2 Pharmacokinetic Parameters 
When possible, the exposure of roflumilast and its major N-oxide metabolite will be calculated 
based on plasma concentrations versus time profile data.  
Pharmacokinetic parameter estimates for roflumilast and its N-oxide metabolite will be 
calculated by a standard noncompartmental method of analysis; these may include AUClast, Cmax, 
Tmax, and others, as data permit. Pharmacokinetic parameters will be summarized using 
appropriate descriptive statistics. 
A detailed description of the PK analysis will be presented in the pharmacokinetics report.  
8.1.3 Determination of Sample Size 
The sample size will be approximately 20 subjects. 
This sample size is considered adequate for safety and PK evaluation.  The sample size was not 
powered based on data for the efficacy endpoints to provide statistical significance. 
8.1.4 Subjects to Analyze 
Safety population will include all subjects who are enrolled and received at least one confirmed 
dose of investigational product. This population will be defined separately for each cohort. 
All subjects who are enrolled and receive at least one application of study drug and have 
evaluable PK data will be included in the pharmacokinetic population. 
The MUSE PK subset population will include all evaluable (see Section 8.1.1 above) subjects 
receiving the active drug with sufficient plasma concentrations of roflumilast to define a profile, 
as determined by the pharmacokineticist. 
8.1.5 Interim Analysis 
No interim efficacy analyses are planned.  PK and safety data may be reviewed on an ongoing 
basis. 
8.1.6 Background and Demographic Characteristics 
Descriptive statistics will be used to summarize demographic characteristics (age, sex, ethnicity, 
and race) and background characteristics for the enrolled subjects.   
8.1.7 Investigational Product Application Compliance 
The number of investigational product applications by each subject based on diary data will be 
summarized using descriptive statistics.  
The amount of investigational product used by each subject based on tube weight will be 
summarized by treatment using descriptive statistics, and categorically.  


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Investigational product application compliance will be calculated based on number of 
applications divided by the expected number (amount) of  investigational product applications 
for each subject.  Compliance will be summarized descriptively by treatment group. 
8.2 
Efficacy Evaluation 
8.2.1 Exploratory Endpoints 
The Exploratory Efficacy Endpoints will include: 
• Change and percent change from baseline in PASI score at each study visit 
• Achievement of a 50% or greater, 75% or greater improvement in PASI score from 
baseline to each study visit 
• Change and percent change from baseline in IGA score at each study visit  
• Change and percent change from baseline in I-IGA score at each study visit  
• Change and percent change from baseline in BSA score at each study visit  
• Change and percent change from baseline in WI-NRS score at each study visit  
Descriptive statistics will be calculated for quantitative efficacy data and frequency counts will 
be compiled for classification of categorical efficacy data.   
8.3 
Safety Evaluation 
Descriptive statistics will be calculated for quantitative safety data and frequency counts will be 
compiled for classification of qualitative safety data.  
8.3.1 Adverse Events 
All treatment-emergent AEs occurring during the study will be recorded and classified on the 
basis of MedDRA terminology for the safety population. Treatment-emergent AEs are those AEs 
with an onset on or after application of investigational product at the Baseline visit or were 
present at treatment initiation but worsened during treatment, through study completion. 
All treatment-emergent AEs will be summarized by cohort, the number of subjects reporting 
treatment-emergent AEs, system organ class, preferred term, severity, relationship, 
and seriousness. 
Serious adverse events (SAEs) will be listed by subject. SAEs will be summarized by severity, 
and relationship to study treatment. Each subject will be counted only once within a system 
organ class or a preferred term using the event with the greatest relationship and greatest 
severity. 
All information pertaining to AEs noted during the study will be listed by subject, detailing the 
verbatim description given by the Investigator, preferred term, system organ class, start date, 
stop date, severity, action taken regarding study drug, corrective treatment, outcome, and drug 
relatedness. The event onset will also be shown relative (in number of days) to date of first 


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application. In addition, a list of subjects who prematurely discontinue from the study due to 
adverse events will also be provided. 
8.3.2 Local Tolerance Assessment 
For the Investigator’s assessment the numeric application site reaction scores will be summarized 
individually by using number and percentage of subjects by visit. 
8.3.3 Medical History and Physical Examinations 
Physical examinations will be performed at Screening, Baseline and Week 4, and 12-lead ECGs 
will be performed at Screening and Week 4. Medical history and Physical Examination findings 
will be listed by subject. Clinically significant physical examination parameters will be captured 
as adverse events. Changes in physical examinations will be described in the text of the final 
report. 
ECGs will be tabulated by visit within each cohort. 
8.3.4 Clinical Laboratory Results and Vital Signs 
All clinical laboratory results and vital signs measurements and their change from baseline 
(pre-dose), will be summarized along with time point of collection. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory results.  
A shift table will identify subjects who gain or lose >5% body weight over the course of the 
study. 
8.3.5 Prior and Concomitant Medications 
Prior and concomitant medication information for all randomized subjects will be presented in a 
by-subject listing.  Summary tables will be presented by World Health Organization-Anatomical 
Therapeutic Chemical Classification System (WHO-ATC) therapeutic category and product. 
9 
STUDY ADMINISTRATION 
9.1 
Ethics 
9.1.1 Ethics Review Board  
Before enrollment of subjects into the study, the current protocol and ICF will be reviewed and 
approved by an appropriate IRB or EC, as required by FDA (21 CFR § 56), Health Canada, 
and ICH GCP regulations.  A letter documenting the IRB or EC approval must be received by 
the Sponsor (or delegate) before the initiation of the study at a clinical site. Amendments to the 
protocol will be subject to the same requirements as the original protocol.  
The Investigator, Sponsor, or designee will submit a progress report at least once yearly to the 
IRB or EC. However, the frequency of these reports will depend on IRB or EC requirements. 
As soon as possible after completion or termination of the study, the Investigator will submit a 


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final report to the IRB or EC per the IRB or EC requirements, and in compliance with FDA and 
Health Canada regulations and ICH GCP guidelines. 
The Investigator, the Sponsor, or designee shall promptly notify the IRB or EC of any SAEs, 
SUSARs, or any other information that may affect the safe use of investigational product  during 
the study, per the IRB or EC local requirements, and in compliance with FDA and Health 
Canada regulations and ICH GCP guidelines. 
9.1.2 Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, the principles of the 
Tri-Council Policy Statement (TCPS), the ethical principles set forth in the Declaration of 
Helsinki, and the ICH harmonized tripartite guideline regarding GCP (E6 Consolidated 
Guidance, April 1996). 
9.1.3 Subject Information and Consent/Assent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and date 
an ICF summarizing the discussion prior to screening and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. Adolescents will 
provide written assent and parent(s) or legal guardian(s) will provide written consent for all 
subjects, as required by local law. 
Subjects will be given a signed copy of their ICF. 
9.2 
Study Monitoring 
Prior to the initiation of the clinical investigation, Sponsor representatives or designees may visit 
the clinical site where the investigation is to be conducted.  Sponsor representatives shall ensure 
that the Investigator understands the investigational status of the investigational product, 
all requirements of the investigation to be undertaken, and all of his/her responsibilities as an 
Investigator.  Sponsor representatives will also visit the clinical site at appropriate intervals as 
required to ensure compliance with the protocol and to verify the accuracy and completeness of 
data reported on the CRFs.  The Study Director or designees shall be available for consultation 
with the Investigator and serve as liaisons between the clinical site and the Sponsor. 
The Sponsor or authorized designees may inspect all documents and records required to be 
maintained by the Investigator, including but not limited to medical records (office, clinic, 
or hospital) and investigational product dispensation logs for the subjects in this clinical 
investigation.  The Investigator must permit access to such records.  The Investigator must 
obtain, as part of informed consent, permission for an authorized representative of the Sponsor, 
or regulatory authorities, to review, in confidence, any records identifying subjects. 


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9.3 
Study Completion/Termination 
9.3.1 Study Completion 
The study is considered completed with the last visit of the last subject participating in the study. 
The final data from the investigational site will be sent to the Sponsor (or designee) after 
completion of the final subject visit at that site, in the time frame specified in the Clinical Trial 
Agreement. 
9.3.2 Study Termination 
The Sponsor reserves the right to close the investigational site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Investigational sites will be closed upon 
study completion. An investigational site is considered closed when all required documents and 
study supplies have been collected and a site closure visit has been performed. The investigator 
may initiate site closure at any time, provided there is reasonable cause and sufficient notice is 
given in advance of the intended termination. 
Reasons for the early closure of an investigational site by the Sponsor or investigator may 
include but are not limited to: 
• Failure of the investigator to comply with the protocol, the Sponsor’s procedures, or GCP 
guidelines. 
• Inadequate recruitment of subjects by the investigator. 
• Discontinuation of further drug development. 
9.4 
Data Quality Assurance 
In order to ensure the collection of accurate, 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 100% quality control check prior to clinical database lock. 
Edit checks are then performed for appropriate databases as a validation routine using SAS® to 
check for missing data, data inconsistencies, data ranges etc. Corrections are made prior to 
database lock. 
9.5 
Data Handling and Record Keeping 
During the clinical study, the Investigator will maintain adequate records, including medical 
records, records detailing the progress of the study for each subject, laboratory reports, signed 
informed consent forms, investigational product disposition records, correspondence with the 
IRB and Study Monitor/Sponsor, AE reports, and information regarding subject discontinuation 
and completion of the clinical investigation. 


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Arcutis Biotherapeutics, Inc. 
Amendment 1 
 
22 Jan 2021 
Confidential 
Page 56 of 74 
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 test article for investigation.  If this requirement differs from any local 
regulations, the local regulations will take precedence unless the local retention policy is less 
than 2 years.   
9.6 
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)/EC(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/EC, 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)/EC(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)/EC(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. 
9.7 
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 Inc., including but not limited 
to the investigator brochure, this protocol, CRF/eCRF, the IP, and any other study information, 
remain the sole and exclusive property of Arcutis 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 Inc. The investigator further agrees to take all reasonable precautions to prevent the 


Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
 
22 Jan 2021 
Confidential 
Page 57 of 74 
disclosure by any employee or agent of the study site to any third party or otherwise into the 
public domain. 
9.8 
Conflict of Interest 
All study investigators will provide documentation of their financial interest or arrangements 
with Arcutis Inc., or proprietary interests in the IP under study. This documentation must be 
provided prior to the investigator’s participation in the study. All investigators with reported 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to 
their participation in the design and conduct of this study. 
9.9 
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).  
9.10 Publication Policy 
The Sponsor is supportive of publishing clinical trial findings.  The process of coordinating 
publication efforts is detailed in the Clinical Trial Agreement. 


Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
 
22 Jan 2021 
Confidential 
Page 58 of 74 
10 REFERENCES 
Augustin M, Glaeske G, Radtke MA, et al. Epidemiology and comorbidity of psoriasis in 
children. Br J Dermatol. 2010;162(3):633-636. 
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. 
Bethke TD, Böhmer GM, Hermann R, et al. Dose-proportional intraindividual single-and 
repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 Inhibitor. 
J Clin Pharmacol. 2007;47:26-36. 
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. 
Bronckers IM, Paller AS, van Geel MJ, et al. Psoriasis in children and adolescents: Diagnosis, 
management and comorbidities. Paediatr Drugs. 2015;17(5):373-84.  
DALIRESP (roflumilast) tablets [package insert]. AstraZeneca Pharmaceuticals LP, Wilmington, 
DE USA; 2018. 
EUCRISA™ (crisaborole) ointment, 2%, for topical use [package insert]. Pfizer Laboratories 
Div. Pfizer Inc, NY, USA; 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 3.0, 08 October 2019. 
Michalski JM, Golden G, Ikari J, et al. PDE4: A Novel Target in the Treatment of Chronic 
Obstructive Pulmonary Disease. Clin. Pharmacol. Ther. 2012;91:134–142. 
OTEZLA® (apremilast) tablets, for oral use [package insert].  Celgene Corporation, Summit, NJ 
USA; 2017 
Wedzicha JA, Calverley PMA, Klaus FR.  Roflumilast: a review of its use in the treatment of 
COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2016;11:81-90. 
 




Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 January 2021  
Confidential 
Page 60 of 74 
Appendix 2. Children’s Depression Inventory 2 (Parent Report) 
 
 
 




Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 January 2021  
Confidential 
Page 62 of 74 
Appendix 4. Children’s Dermatology Life Quality Index (CDLQI) 
 
CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX 
 
Subject Number:  
 
Diagnosis: 
 
 
 
 
 
CDLQI  
Age: 
 
 
 
Date: 
 
 
 
 
 
 
SCORE: 
 
The aim of this questionnaire is to measure how much your skin problem has 
affected you OVER THE LAST WEEK.  Please tick  one box for each question. 
 
1. 
Over the last week, how itchy, "scratchy",  
 
 
              Very much 
□ 
 
sore or painful has your skin been? 
 
  
 
              Quite a lot 
□ 
 
 
  
 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
2. 
Over the last week, how embarrassed 
 
 
 
             Very much 
□ 
 
or self conscious, upset or sad have you  
 
 
 
             Quite a lot 
□ 
 
been because of your skin? 
 
  
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
3. 
Over the last week, how much has your  
 
 
 
             Very much 
□ 
 
skin affected your friendships? 
  
 
 
 
             Quite a lot 
□ 
 
 
 
 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
4. 
Over the last week, how much have you changed 
 
 
             Very much 
□ 
 
or worn different or special clothes/shoes  
 
 
             Quite a lot 
□ 
 
because of your skin? 
 
 
 
 
 
             Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
5. 
Over the last week, how much has your  
 
 
 
            Very much 
□ 
 
skin trouble affected going out, playing, 
 
 
 
             Quite a lot 
□ 
 
or doing hobbies? 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
6. 
Over the last week, how much have you 
  
 
 
          
Very much 
□ 
 
avoided swimming or other sports because  
 
                           Quite a lot 
□ 
 
of your skin trouble? 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
7. 
Last week, 
 
  
If school time: Over the  
           
Prevented school □  
             
last week, how much did  
               Very much 
□ 
 
school time?   
 
            your skin problem affect your 
             Quite a lot 
□ 
 
 
 
 
 
school work? 
 
 
 
Only a little 
□ 
 
   OR 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
 
was it 
 
 
   
If holiday time: How much 
 
Very much 
□ 
 
holiday time?  
   
               over the last week, has your 
 
Quite a lot 
□ 
 
 
 
 
 
skin problem interfered with 
 
Only a little 
□ 
 
 
 
 
 
your enjoyment of the holiday? 
              Not at all 
□ 
was it 


Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 January 2021  
Confidential 
Page 63 of 74 
8. 
Over the last week, how much trouble  
 
 
 
             Very much 
□ 
 
have you had because of your skin with 
 
 
 
             Quite a lot 
□ 
 
other people calling you names, teasing, 
 
 
 
            Only a little 
□ 
 
bullying, asking questions or avoiding you? 
 
 
             Not at all 
□ 
 
9. 
Over the last week, how much has your sleep  
 
 
             Very much 
□ 
 
been affected by your skin problem? 
 
 
 
              Quite a lot 
□ 
 
 
 
 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
 
 
Not at all 
□ 
 
10. 
Over the last week, how much of a   
 
 
 
              Very much 
□ 
 
problem has the treatment for your  
 
 
 
              Quite a lot 
□ 
 
skin been? 
 
 
 
 
 
 
 
Only a little 
□ 
 
 
 
 
 
 
 
 
  
 
Not at all 
□ 
Please check that you have answered EVERY question. Thank you.  
 
M.S. Lewis-Jones, A.Y. Finlay, May 1993, This must not be copied without the permission of the authors. 
 
 


















Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 Jan 2021 
Confidential 
 Page 72 of 74 
Appendix 6. COVID-19 Study Site Guidance 
 
BACKGROUND 
As the impact of coronavirus disease 2019 (COVID-19) continues to develop, Paidion Research 
Inc. and Arcutis Biotherapeutics Inc. have collated the following guidelines for study sites 
participating in the ARQ-151-215 study. While it is ideal for subjects to perform all 
protocol-specific assessments at the study site, both Paidion 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 EDC 
system. 
 
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.  
 
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: 
• WI-NRS 
• CDLQI 
• CDI-2 
• Subject Local Tolerability 
• Adverse Events 
• Concomitant medication 
• Review of Subject Diary 


Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 Jan 2021 
Confidential 
 Page 73 of 74 
The following Investigator assessments cannot be completed via telemedicine/remotely: 
• IGA, I-IGA 
• PASI 
• 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 clinic, 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 4 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 4 visit versus 
having an Early Termination and no Week 4 visit. If it is not possible for a subject to 
return on-site within window for the Week 4 visit, sites should: 
a. Ensure the subject has signed the most current IRB approved ICF with the ICF 
Addendum. 
b. Contact subjects to discuss continued administration of IP and continue to complete 
their dosing diaries per regular IP administration instructions. 
c. Subjects are approved to continue applying IP post Week 4 as long as the following 
have been discussed with the subject: 


Protocol ARQ-151-215 
Arcutis Biotherapeutics, Inc. 
Amendment 1 
22 Jan 2021 
Confidential 
 Page 74 of 74 
- 
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 that 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 pregnancy test can 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 Week 4 until they 
return the clinic for the Week 4 visit. After this, sites should reach out to the 
Medical Monitor and/or Arcutis directly for approval to have subjects continue 
dosing. 
- 
All the above discussions must be documented in the source. 
d. If available, home health nurse visits could be considered for collection of Vital Signs 
and Clinical Labs. 
e. In the event a subject is quarantined, has symptoms, or is confirmed positive for 
COVID-19, it is the Sponsor’s opinion that IP can continue, assuming no other 
contraindications.  
 

SAP_001.pdf: 
1
Statistical Analysis Plan 
Protocol Title 
An Open Label, 4-Week, Phase 2, Maximal Usage 
Pharmacokinetics and Safety Study of ARQ-151 Cream 
0.3% Administered QD in Pediatric Subjects (ages 6 to 
11 years old) with Plaque Psoriasis 
Protocol Number: 
ARQ-151-215 
Protocol Version: 
Amendment 1 Final  22 January 2021 
SAP Version: 
2 
Date:  
March 2, 2022 
Sponsor:  
Arcutis Biotherapeutics, Inc. 
2945 Townsgate Road, Suite 110 
Westlake Village, CA 91361 
Author: 
Ryan McBride 
Instat Services 
This study will be conducted in compliance with the protocol, Good Clinical Practice 
and all other applicable regulatory requirements, including the archiving of 
essential documents. 
Confidential Information 
No use or disclosure outside Arcutis Biotherapeutics, Inc is permitted without prior 
written authorization from Arcutis Biotherapeutics, Inc.


Arcutis Biotherapeutics, Inc.
Statistical Analysis Plan
Protocol: ARQ-151-215
2MAR2022
2
SAP Document History
Version 
Number
Author
Date 
Change
1
Ryan McBride
23FEB2022
2
Ryan McBride
2MAR2022
Included summary analysis of PK data. 
Some minor grammatical edits.
Signatures / Approvals
VP of Biometrics, Arcutis 
Biotherapeutics, Inc.
Name (Print or Type)
Date
VP of Clinical Development, Arcutis 
Biotherapeutics, Inc.
Name (Print or Type)
Date
Senior Biostatistician, Instat Clinical 
Research
Name (Print or Type)
Date


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
3
Table of Contents
SAP Document History....................................................................................................... 2 
Signatures / Approvals ........................................................................................................ 2 
Table of Contents ................................................................................................................ 3 
List of Abbreviations .......................................................................................................... 5 
1.
Introduction .............................................................................................. 7 
2.
Study Rationale and Objectives ............................................................... 7 
2.1. 
Study Rationale ........................................................................................ 7 
2.2. 
Study Objectives ....................................................................................... 8 
2.2.1. 
Primary Objectives................................................................................... 8 
3.
Study Design ............................................................................................ 8 
3.1. 
Schedule of Visits and Assessments......................................................... 9 
4.
Determination of Sample Size ............................................................... 11 
5.
Statistical Methods ................................................................................. 11 
6.
Analysis Populations.............................................................................. 12 
7.
Study Population .................................................................................... 12 
7.1. 
Subject Disposition ................................................................................. 12 
7.2. 
Protocol Deviations ................................................................................ 12 
7.3. 
Demographic and Baseline Characteristics ............................................ 12 
8.
Efficacy Analysis ................................................................................... 13 
8.1. 
Efficacy Variables .................................................................................. 13 
8.2. 
Baseline Values ...................................................................................... 13 
8.3. 
Handling of Dropouts or Missing Data .................................................. 13 
8.3.1. 
Coronavirus 19 ....................................................................................... 13 
8.4. 
Handling of repeat and unscheduled assessments .................................. 14 
8.5. 
Interim Analysis and Data Monitoring ................................................... 14 
8.6. 
Multiple Comparison/Multiplicity.......................................................... 14 
9.
Methods of Efficacy Analysis................................................................ 14 
9.1. 
Psoriasis Area and Severity Index (PASI).............................................. 14 
9.2. 
Investigator Global Assessment (IGA) and Intertriginous Investigator 
Global Assessment (I-IGA) ................................................................... 15 


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
4
9.3.
Body Surface Area (BSA)...................................................................... 16
9.4. 
Worst Itch-Numerical Rating Scale (WI-NRS) ...................................... 16 
9.5. 
 .......................... 16 
10.
Safety Analysis ...................................................................................... 17 
10.1. 
Exposure and Compliance ...................................................................... 17 
10.2. 
Adverse Events ....................................................................................... 17 
10.3. 
Local Tolerability Assessment ............................................................... 18 
10.4. 
Vital Signs .............................................................................................. 19 
10.5. 
Physical Examination ............................................................................. 19 
10.6. 
Prior and Concomitant Medications ....................................................... 19 
10.7. 
Laboratory Tests ..................................................................................... 20 
10.8. 
Electrocardiogram .................................................................................. 21 
10.9. 
-2) ........................................... 21 
10.10. 
Dermal Imaging ...................................................................................... 21 
11.
Pharmacokinetics ................................................................................... 21 
12.
Planned Tables, Figures, and Listings ................................................... 22 


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
5
List of Abbreviations 
AE 
Adverse Event 
ATC Class 
Anatomical/Therapeutic/Chemical Class 
BSA 
Body Surface Area 
CDI 2 
CDLQI 
Dermatology Life Quality Index 
COVID-19 
Coronavirus Disease 2019 
CSR
Clinical Study Report
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
EOS 
End of Study 
FOCBP 
Female of Childbearing Potential 
IGA 
Investigator Global Assessment 
I-IGA
Intertriginous Investigator Global Assessment 
ITT 
Intent to Treat 
LSR 
Local Skin Reactions 
g 
Microgram 
MedDRA 
Medical Dictionary for Regulatory Activities 
PDE-4 
Phosphodiesterase 4 
PASI 
Psoriasis Area and Severity Index 
PK 
Pharmacokinetics 
QD 
SAE
Serious Adverse Event 
SAP 
Statistical Analysis Plan


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
6
TEAE
Treatment Emergent Adverse Event
WHO
World Health Organization 
WI-NRS 
Worst Itch Numeric Rating Score 


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
7
1.
Introduction
Arcutis, Inc. is condu
n Open-Label, 4-Week, 
Phase 2, Maximal Usage Pharmacokinetics and Safety Study of ARQ-151 Cream 0.3% 
Administered QD in Pediatric Subjects (aged 6 to 11 years old) with Plaque Psoriasis  
The study background, design and subject assessments for the study are described in the 
study specific protocol.  
The statistical methods to be implemented during the analyses of data collected within the 
scope of this study (ARQ-151-215) will be outlined in this document. The purpose of this 
plan is to provide specific guidelines from which the statistical analysis will proceed. Any 
deviations from this plan will be documented in the clinical study report. 
This version of the Statistical Analysis Plan (SAP) addresses this study as described in 
Amendment 1 Final dated 22 January 2021 of the study protocol. 
2.
Study Rationale and Objectives
2.1. Study Rationale 
The past 15 years have witnessed a transformation in the systemic treatment of moderate 
to severe psoriasis with the advent of biological therapies. However, for patients with 
milder forms of disease, best treated with topical options, the therapeutic landscape has not 
significantly changed in several decades. Topical steroids come in all shapes and forms, 
but the lower potency steroids are not effective and the higher potency steroids are best 
with issues of local skin atrophy and the potential for hypothalamic-pituitary axis 
suppression when applied over larger body surface areas and for prolonged periods of time. 
Vitamin D has been the other staple of topical psoriasis treatment, but it is irritating, not 
suitable for use on the face or intertriginous areas, and its efficacy is rather modest. Hence, 
there is a substantial medical need for additional topical approaches in the treatment of 
psoriasis. The study Sponsor is developing a topical cream formulation of roflumilast for 
the treatment of chronic plaque psoriasis. Phase 2 results suggest that ARQ-151 may be a 
highly efficacious and well-tolerated topical treatment for psoriasis. Accordingly, a phase 
3 program is ongoing evaluating ARQ-151 cream 0.3% for the treatment of plaque 
psoriasis in subjects 2 years of age and older. The present study is a maximal use 
pharmacokinetic trial with the to-be-marked formulation. The study is designed to ensure 
that the expected target patient population for ARQ-151 is properly represented, as well as 
to ensure that a suitable number of subjects with plaque psoriasis are evaluated and that PK 
is adequately characterized. 


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
8
2.2. Study Objectives 
2.2.1. 
Primary Objectives 
The primary objectives are: 
To evaluate the systemic exposure and characterize the plasma pharmacokinetic 
(PK) profile of ARQ-151 cream 0.3% and its major N-oxide metabolite, in pediatric 
subjects with plaque psoriasis involving body surface areas (BSA) of at least 3%. 
To evaluate the safety of ARQ-151 cream 0.3% applied QD to pediatric subjects 
with plaque psoriasis involving BSA of at least 2%.  
To explore the efficacy of ARQ-151 cream 0.3% applied QD for 4 weeks to 
pediatric subjects with plaque psoriasis involving BSA of at least 2%.  
3.
Study Design
This is a phase 2, open label maximal usage PK and safety study of ARQ-151 cream 0.3% 
in pediatric subjects (ages 6 to 11 years old) with plaque psoriasis. 
At entry, subjects will have at least 2% BSA involvement (excluding the scalp, palms, 
soles), except for a subset of evaluable subjects who consent to a PK sampling for maximal 
usage evaluation that will have at least 3% BSA involvement (excluding the scalp, palms, 
so
Subjects who discontinue the study may be replaced. 
Subjects/caregivers will apply ARQ-151 cream 0.3% QD for 28 days to all affected areas 
of plaque psoriasis and any newly appearing plaque psoriasis lesions that arise during the 
study, except on the scalp. Subjects/caregivers should maintain treatment of these areas 
with study drug for the duration of the study regardless of whether treatable areas of plaque 
psoriasis clear prior to Week 4. The palms and soles will be treated but will not be counted 
towards any measurements of efficacy (PASI, IGA, I-IGA, BSA). 


Arcutis Biotherapeutics, Inc. 
Statistical Analysis Plan 
Protocol: ARQ-151-215 
2MAR2022 
9
3.1. Schedule of Visits and Assessments 
Study Procedure 
Screening 
Baseline
Day 1 
Wk 2 
Day 14 
Wk 4 
Day 28/ET 
Wk 5 
Day 35 
Visit 
1 
2 
3 
4 
5 
Visit Window 
-3 weeks
+/- 1 day 
+/- 3 days 
+/- 3 days 
Informed consent/assent 
X 
Demographics 
X 
Medical and surgical history 
X 
Physical examinationa 
X 
X 
X 
I/E criteria 
X 
X 
Hematology, Serum Chemistries, and 
Urine Analysisb
X 
X 
X 
Vital signs, weight, heightc 
X 
X 
X 
X 
IGA, I-IGA, PASI, BSA, WI-NRS, 
CDLQId 
X 
X 
X 
X 
Local cutaneous tolerability assessment
(including Berger & Bowman and 
subject-rated stinging/burning)e 
X 
X 
X 
CDI-2
X 
X 
X 
X 
Serum pregnancy testf 
X 
Urine pregnancy testf 
X 
X 
Resting 12-lead ECG 
X 
X 
PK samplingg 
X 
X 
Drug application and subject/family 
training in clinich 
X 
X 
Dispense investigational product kiti 
X 
X 
Weigh investigational product tubesj 
X 
X 
X 
Dispense/review diary 
X 
X 
X 
Adverse event assessmentk 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
Optional photographyl 
X 
X 
X 
Study Exitm 
X 
a Limited physical examination: skin, lungs, and heart only. 
b To be collected at Screening, Baseline, and Week 4. If Baseline is within 3 weeks of Screening, the 
Screening results will be utilized. 
c Height will be measured at every visit (see Protocol Section 7.1.3 for the recommended procedure). 
Weight will be collected on every visit. Weight should be obtained using a calibrated weight scale 


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and the same scale should be used for a subject throughout the duration of the study. The subject 
should remove shoes and heavy clothing (sweaters or jackets), and empty pockets. The subject
should stand with both feet in the center of the scale with their arms at their side and hold still. 
Record the weight to the nearest decimal fraction (for example, 55.5 pounds or 25.1 kilograms).
Measure the weight in triplicate and report the average weight in EDC. 
d BSA, IGA affected by plaque psoriasis will be determined to qualify for study entry (Screening and 
Baseline) and will be measured at the Week 2 and Week 4 visits. Scalp, palms and soles should be 
excluded from consideration in these assessments. Additionally, Intertriginous Area-IGA (I-IGA), 
PASI, and WI-NRS will be evaluated. WI-NRS pruritus assessment will 
years old, or by parent/caregiver for subjects < 8 years old. All other assessments will be performed 
by the Investigator or study staff, as appropriate. 
e Local tolerability assessments should be recorded prior to study drug application for the Investigator 
assessment of skin irritation (Berger and Bowman skin irritation score) and 10-15 minutes post-drug 
application for the 
-
-rating completed by the 
subject or parent/caregiver). At the Week 4 visit, only the Investigator assessment of skin irritation 
will be performed. Note for investigator tolerability assessments: reactions at the site of product IP 
application, which may occur post-Baseline, should be differentiated from the preexisting 
inflammation associated with the 
 psoriasis. 
f For females that have started menstruation, a serum pregnancy test will be performed during 
Screening. A urine pregnancy test will be administered to all females of child-bearing potential. A 
negative result is required for continued participation in the study, and results must be available 
prior to dispensing of study drug 
g All enrolled subjects will have a trough PK sample collected at the Week 4 visit. A subset of 6 subjects 
who consent will provide an additional PK sample pre-dose (within 1 hour) at the Week 2 visit. 
h Subjects/caregiver to apply assigned IP in clinic at Baseline and Week 2. All Investigator assessments 
should be completed prior to IP application. 
I The number of kits to be dispensed is based on %BSA affected. See IP Handling Manual for details. 
Site should review IP kit to ensure sufficient IP is available until the next visit and only dispense 
additional IP if needed.
j Every tube should be weighed and recorded when dispensed and returned.
k
resolved or otherwise judged as clinically stable. 
l Photography is planned to be performed at selected investigational sites. Photography will be
optional. All efforts will be made to de-identify the subjects.
m Subjects who enroll into the open label extension study (ARQ-151-306) will complete the study at
Week 4; subjects that do not enroll into ARQ-151-306 will complete the study with a Week 5 
Telephone Follow-up. The Week 5 Telephone Follow-up is a call to the subjects to follow-up on any 
continuing adverse events related to the study drug. Telephone call also assesses any emergent 
adverse event post-Visit 4. Any emergent AEs will be followed in the clinic for up to 1 month at the 
 clinically stable. 


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4.
Determination of Sample Size
Approximately 20 male and female subjects ages 6 to 11 years old with plaque psoriasis: 
All subjects must have at least 2% BSA psoriasis involvement at Baseline
However, a subset of 6 evaluable subjects who consent to a PK sample for 
maximal usage evaluation will have at least 3% BSA involvement at Baseline 
(excluding the scalp, palms, soles) 
o
PK evaluable subjects (in the maximal usage subset) are defined as those
that have PK results at Week 2. Unevaluable subjects may be replaced.
) psoriasis severity based on IGA at 
Baseline 
This sample size is considered adequate for PK and safety evaluation. The sample size 
was not powered based on data for the efficacy endpoints to provide statistical 
significance.
5.
Statistical Methods
Summaries may be generated for regulatory interaction prior to the completion of the 
study and an interim report may be written at that time. The statistical analyses will be 
reported using summary tables, figures and listings (TFLs). Numbering for TFLs will be 
based on the recommended numbering convention provided by the International 
Conference on Harmonisation. 
Continuous variables will be summarized with means, standard deviations, medians, 
minimums and maximums. Categorical variables will be summarized by counts and 
percent of subjects in corresponding categories. Unless specified otherwise, baseline 
results will be defined as the closest measurement taken prior to first dose of study 
medication. When applicable, unscheduled visits will be used in the determination of 
baseline values. Missing values are not considered for percent calculations, unless stated 
otherwise. In those cases, footnotes will specify the percent calculation. No formal 
inferential statistics will be performed for this open-label study.  
Individual subject data obtained via the electronic data capture (EDC) system and from 
external vendors will be presented in by subject listings. 
The analyses described in this plan are considered a priori, in that they have been defined 
prior to database lock. Any analysis added after the database lock will be considered post 
hoc and exploratory. Post hoc analyses will be labeled as such on the output and 
identified in the CSR. All analyses and tabulations for the CSR will be performed using 


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SAS  version 9.4 or higher. Tables will be presented in .rtf and .pdf format. Listings will 
be presented in .pdf format. Upon completion, all SAS programs will be validated by an 
independent programmer. The validation process will be used to confirm that statistically 
valid methods have been implemented and that all data manipulations and calculations 
are accurate. Checks will be made to ensure accuracy, consistency with this plan, 
consistency with tables and consistency between tables and corresponding data listings.  
6.
Analysis Populations
Subjects who enroll into the study need to sign inform consent and receive at least one 
confirmed dose of investigational product. 
The Safety population will include all subjects who are enrolled and received at least one 
confirmed dose of investigational product. This population will be used for safety and 
efficacy analyses. 
The Pharmacokinetic (PK) population will include all subjects who have who received at 
least 1 confirmed dose of IP with sufficient plasma concentrations of roflumilast to define 
a profile, as determined by the pharmacokinetics. 
7.
Study Population
7.1. Subject Disposition 
Information regarding subject disposition will be summarized for all subjects. Summaries 
will include the number of the subjects who were screened, who failed the screen, who 
enrolled into the study, the subject number in each analysis population, the number of the 
subjects who completed the study and who discontinue the study early. For those who 
discontinue the study, the primary reason for discontinuation will be summarized.  
7.2. Protocol Deviations 
Protocol deviations will be collected throughout the duration of the study. Protocol 
deviations will be assigned a sponsor-defined category type, such as treatment 
compliance, study adherence, and use of prohibited therapies. Each deviation will be 
defined as important or minor. A tabular summary of the important deviations will be 
generated. In addition, a by-subject listing of all the protocol deviations will be produced. 
7.3. Demographic and Baseline Characteristics 
Demographics and baseline characteristic data will include age, sex, ethnicity, race, body 
weight (kg), height (cm), and baseline disease characteristics [BSA, BSA group (>=5% 
or <5%), IGA, I-IGA, PASI, and WI-NRS baseline scores]. Medical history will not be 
summarized in a table but will be displayed in a listing. 


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Continuous variables will be summarized using descriptive statistics. Categorical 
variables will be summarized using counts and percentages. Demographics and baseline 
characteristics will be summarized for the Safety population. 
8.
Efficacy Analysis
The Safety population will be used for efficacy analysis. Analyses using the Safety 
population will be based on treatment received. 
8.1. Efficacy Variables 
Efficacy will be an exploratory endpoint, with analyses including: 
Change and percent change from baseline in PASI score at each study visit  
Achievement of a 50% or greater and 75% or greater improvement in PASI score 
from baseline to each study visit
Change and percent change from baseline in IGA score at each study visit 
Change and percent change from baseline in I-IGA score at each study visit 
Change and percent change from baseline in BSA involvement at each study visit 
Change and percent change from baseline in WI-NRS score at each study visit 
8.2. Baseline Values 
Unless otherwise noted, baseline is defined as the last non-missing value recorded prior 
to the first application of study drug. When applicable, unscheduled visits will be used in 
the determination of baseline values. 
For subject local tolerability assessment, baseline is derived as the last non-missing 
measurement taken on Day 1 of first application of study drug. Baseline investigator local 
tolerability assessment is the last non-missing assessment prior to the first dose. 
8.3. Handling of Dropouts or Missing Data 
Subjects that withdraw or are discontinued from the study prior to Week 4 Visit, may be 
replaced. Unless described otherwise in subsequent sections, analyses will be carried out 
with the data available using no imputation for missing data. A description of how 
missing data will be handled for select endpoints is included below.  
8.3.1. 
Coronavirus 19 
Due to coronavirus disease 19 (COVID-19) outbreak during the course of the study, there 
may be several subjects who will have missing assessments which could affect the 
analysis. Subjects who are unable to attend a study visit due to COVID-19 will be 
documented in the protocol deviation log. The protocol deviation date will be used as the 
COVID-19 affected date (or visit). If a subject reports an adverse event of COVID-19, 


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then the event start date will be used as the affected date. In the event that a subject has 
an affected COVID-19 date from both sources, the earlier of the dates will be used. 
Subjects who were affected by COVID-19 will be summarized in a data listing. The 
listing will contain the following information: subject number, treatment, gender, age, 
total study duration, exposure to study treatment, any COVID-19 related adverse events, 
completion/discontinuation of the study, and reasons for discontinuation. 
8.4. Handling of repeat and unscheduled assessments 
Unscheduled assessments are used when scheduled assessments are not collected. 
Unscheduled assessments will be assigned to the associated visit and timepoint based on 
date and time of assessment. If there are multiple unscheduled assessments assigned to 
the same visit, then the assessment closest to the scheduled visit will be used for analysis. 
8.5. Interim Analysis and Data Monitoring 
No interim efficacy analyses are planned. PK and safety data may be reviewed on an 
ongoing basis. Summaries may be generated for regulatory interaction. 
8.6. Multiple Comparison/Multiplicity 
No formal statistical comparisons are planned; thus, no adjustment for multiple 
comparisons is needed. 
9.
Methods of Efficacy Analysis
9.1. Psoriasis Area and Severity Index (PASI) 
Psoriasis Area and Severity Index (PASI) assessment will be summarized at 
Baseline/Day 1, Week 2, and Week 4 visits. Assessments will be performed as single 
assessments from which PASIs will be calculated. 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); 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/mPASI. 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


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5. 70-89% of involved area
6. 90-100% of involved area
Within each area, the severity is estimated by four clinical signs: erythema (
), 
T
hickness), 
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  
Descriptive statistics will be calculated for percent change from baseline and change from 
baseline in PASI score at each study visit. Improvement in PASI scores will be 
summarized at each study visit. For example, 75% improvement (PASI75) from baseline 
is when the percent change from baseline is 75% or greater and 50% or greater 
improvement (PASI50) from baseline is when percent change from baseline is at least 
50%. Frequency counts and percentages will be compiled for PASI75 and PASI50 scores 
at each study visit. 
9.2. Investigator Global Assessment (IGA) and Intertriginous 
Investigator Global Assessment (I-IGA) 
Investigator Global Assessment (IGA) will be summarized at Baseline, Week 2, and 
Week 4. The IGA should be completed prior to other physician assessments. The IGA is 
a static evaluation of qualitative overall psoriasis severity. This global assessment scale is 
an ordinal scale 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 (see Table below). Descriptive statistics will be calculated for 
change and percent change from baseline in IGA score at each study visit. IGA success is 
>= 2-grade improvement from baseline. The proportion of subjects who achieved IGA 
success will be summarized at each visit. 
Score 
Morphological 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 


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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 
-
areas ONLY and NOT whole body involvement), an IGA for the intertriginous region 
alone (I-IGA) will be summarized at Baseline, Week 2, and Week 4. Descriptive statistics 
will be calculated for change and percent change from baseline in I-IGA score at each 
study visit along with I-IGA score at each visit. 
9.3. Body Surface Area (BSA) 
Body surface area assessments will be summarized at Baseline, Week 2, and Week 4. 
The BSA affected by plaque psoriasis 
surface area (BSA). Descriptive statistics will be calculated for change and percent 
change from baseline at each study visit. 
9.4. Worst Itch-Numerical Rating Scale (WI-NRS) 
WI-NRS Assessments will be summarized at Baseline, Week 2, and Week 4. 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 aski
WI-NRS 
subjects < 8 years old. Descriptive statistics will be calculated for change and percent 
change from baseline in WI-NRS pruritus score at each study visit. WI-NRS success is 
defined as achievement of WI-NRS of 4-point reduction from baseline in subjects who 
had baseline WI-NRS >=4. The WI-NRS success rate will be summarized at each visit.  
9.5. 
 
-16) will be completed at 
Screening, Baseline, Week 2, and Week 4. CDLQI allows a simple, compact and uniform 
assessment of patients with skin diseases in general, in which higher scores indicate 
poorer disease-related quality of life. Subject/caregivers will complete the CDLQI. 
CDLQI will be displayed in a by-subject listing.  


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10. 
Safety Analysis 
All safety analysis will be based on the Safety Population. Analysis using the Safety 
population will be based on the treatment received. 
10.1. 
Exposure and Compliance 
The number of IP applications by each subject based on diary data will be summarized 
using descriptive statistics appropriate for continuous variables. The amount of IP used 
by each subject based on tube weight will be summarized descriptively using continuous 
methods. The number of days on IP will be summarized descriptively.  
A subject will be considered compliant with the dosing regimen if the subject applies at 
least 80% of the expected applications during the IP application period and does not miss 
more than 3 consecutive doses. 
Investigational product application compliance will be calculated based on number of 
applications divided by the expected number of IP applications. Compliance will be 
summarized descriptively using the following categories: 100%, 
- <100%, < 80%. 
10.2. 
Adverse Events 
All the adverse events will be coded based on MedDRA version 23 or higher version.  
Treatment emergent adverse events (TEAEs) are those adverse events (AEs) with an 
onset on or after first application of investigational product or were present at treatment 
initiation but worsened during treatment, through study completion. Pre-treatment AEs 
and AEs reported after study completion will be listed but not included in TEAE 
summaries. If it cannot be determined whether the AE is treatment emergent due to an 
incomplete (partial) onset date, then the AE will be considered to be treatment emergent. 
Overall summary will be presented, which will include the total number of events, and 
the number and percentage of subjects who experienced TEAE, TEAE by the strongest 
relationship, TEAE by the maximum severity, treatment-emergent serious AE (TESAE), 
TEAE leading to study discontinuation, and TEAE leading to death.   
Each AE summary will be displayed. Summaries of the following types will be 
presented: 
 Subject count and incidence rate of TEAEs by MedDRA system organ class and 
preferred term. Summaries will be ordered by descending order of incidence of 
system organ class and preferred term within each system organ class 
 Subject count and incidence rate of TEAEs by MedDRA preferred term in 
descending order. 
 Subject count and incidence rate of TEAEs by MedDRA system organ class, 
preferred term and maximum severity. At each level of subject summarization, a 


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subject is classified according to the maximum severity if the subject reported one 
or more events. 
 Subject count and incidence rate of treatment related TEAEs by MedDRA system 
organ class and preferred t
Unrelated
Unlikely
 
Likely
A subject is classified according 
to the closest relationship if the subject reported one or more events. Adverse 
events with missing relationship will be considered treatment related.  
 Subject count and incidence rate of Serious TEAEs by MedDRA system organ 
class and preferred term. Each subject will be counted only once within a system 
organ class or a preferred term using the event with maximum severity. 
 Subject count and incidence rate of TEAEs leading to study treatment 
discontinuation by MedDRA system organ class and preferred term if there is 
any. 
All information pertaining to AEs noted during the study will be listed by subject, 
detailing the verbatim description given by the Investigator, preferred term, system organ 
class, start date, stop date, severity, action taken regarding study drug, corrective 
treatment, outcome, and drug relatedness along with the treatment emergent flag and 
subjects who prematurely discontinued from study flag. The event onset will also be 
shown relative (in number of days) to date of first application.  
10.3. 
Local Tolerability Assessment 
Investigator Local Tolerability Assessments will be summarized at Baseline, Week 2, and 
Week 4. Irritation reactions are graded using the following dermal response scale below. 
The investigator assessments will be conducted by the investigator prior to study drug 
application in the clinic. 
Dermal Response
0 = no evidence of irritation 
1 = minimal erythema, barely perceptible 
2 = definite erythema, readily visible; minimal edema or minimal papular 
response 
3 = erythema and papules
4 = definite edema 
5 = erythema, edema and papules 
6 = vesicular eruption 
7 = strong reaction spreading beyond application site  
 


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Other Effects
A = slight glazed appearance  
B = marked glazing 
C = glazing with peeling and cracking 
D = glazing with fissures 
E = film of dried serous exudates 
F = small petechial erosions and/or scabs 
G = no other effects 
The investigator assessments will be conducted by the investigator prior to study drug 
application in the clinic. Frequency counts and percentages of the numeric application 
site reaction scores will be summarized at each study visit. Any additional information 
that are not included in the 
summaries will be presented in listings. 
The Subject Local Tolerability Assessment will be summarized at Baseline and Week 2. 
This assessment will be administered by the site 10 to 15 minutes after study drug 
application in the clinic at Baseline and at Week 2. Response may be by the patient 
and/or parent/caregiver, as deemed appropriate by the Investigator.  
Grade 
Sensation following Drug Application 
0 (none) 
No sensation 
1 (mild) 
Slight warm, tingling sensation; not really bothersome 
2 (moderate) 
Definite warm, tingling sensation that is somewhat bothersome 
3 (severe) 
Hot, tingling/stinging sensation that has caused definite discomfort 
 
10.4. 
Vital Signs 
Vital signs measurements and their change from baseline will be summarized at each 
study visit. A shift table will identify subjects who gain or lose >5% body weight over the 
course of the study. 
10.5. 
Physical Examination 
Physical examinations will be performed at Screening, Baseline, and Week 4. Clinically 
significant physical examination parameters will be capture as adverse events. Physical 
examination and abnormal values will be listed in a listing. No summary tables of 
physical examination are planned. Changes in physical examination will be described in 
the text of the final report. 
10.6. 
Prior and Concomitant Medications 
Prior and concomitant medication verbatim terms captured via the EDC system will be 
mapped to Anatomical/Therapeutic/Chemical (ATC) class and Preferred Names using the 


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World Health Organization (WHO) Drug Dictionary Enhanced version B3 March 2019 
or later. Prior medications are any medication with onset prior to first dose of treatment, 
even if the medication is continued after first dose. Concomitant medications are any 
medication with first dose on or after the day of first dose of treatment. 
Prior and concomitant medications will be summarized by WHO ATC class and 
preferred name. These summaries will present the number and percent of subjects using 
each medication. Subjects may have more than one medication per preferred name. A 
subject is counted once if one or more medications is reported for the subject. Each 
summary will be ordered by descending order of incidence of ATC class and preferred 
term. 
10.7. 
Laboratory Tests 
Laboratory tests will be summarized at Baseline and Week 4. All tests listed in the table 
below will be collected in a non-fasting state (no food restrictions). In addition, 
laboratory safety tests may be performed at various unscheduled timepoints, if deemed 
necessary by the Investigator. All laboratory tests will be summarized (baseline, 
observed, change from baseline and percent change from baseline) by presenting 
descriptive statistics (number of subjects, mean, standard deviation, median, Q1, Q3, 
minimum, and maximum). A shift table describing out-of-normal range shifts will be 
provided for clinical laboratory results.  
Hematology 
Serum Chemistry 
Hemoglobin 
Blood Urea Nitrogen 
Hematocrit 
Bilirubin (total and direct) 
Total and differential leukocyte count
Alkaline phosphatase 
Red blood cell count with indices and morphology 
Aspartate aminotransferase 
Platelet count 
Alanine aminotransferase 
 
Albumin 
 
Sodium 
 
Potassium 
 
Chloride 
 
Glucose 
 
Creatinine 
Urinalysis 
Additional Tests 
pH 
Urine pregnancy test ** 
(for females of childbearing potential only) 
Specific gravity 
Serum pregnancy test (hCG)*** 
Protein* 
 
Glucose 
 
Ketones 
 
Bilirubin
 
Blood* 
 


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Nitrite* 
Urobilinogen 
Leukocyte esterase* 
*
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.
**
At baseline and Week 4 for FOCBP only
*** 
At screening only
10.8. 
Electrocardiogram 
12-lead electrocardiograms (ECGs) will be performed at Screening and Week 4. ECGs
will be performed on subjects after 5 minutes in the supine position. ECGs will be
summarized with descriptive statistics at each study visit.
10.9. 
 (CDI-2)
The CDI-2 assessment will be summarized at Baseline, Week 2, and Week 4. The CDI-2 
quantifies depressive symptomatology and is recommended for use in initial evaluation 
and is appropriate when there is a need for an assessment and robust description of a 
Parent Report Form. The total 
score is the sum of the responses for the 17 questions. Total score, functional score, and 
emotional score will be summarized descriptively at each study visit.  
CDI-2 total score is a sum of the 17 questions (individual questions scored as much or
most of the time=3, often=2, some of the time=1, Not at all=0; range for score 0 to 51).
CDI-2 emotional problem scale is a sum of 9 questions (Q1, Q3-6, Q8, Q10-12)
CDI-2 function problem scale is a sum of 8 questions (Q2, Q7, Q9, Q13-17)
10.10. 
Dermal Imaging
Medical photography will be performed at participating sites on consenting/assenting 
subjects and summarized at Baseline, Week 2, and Week 4. Subjects who are unwilling 
to participate in the medical photography will be allowed to opt out of this procedure and 
document on the informed consent form. Medical photography information will be 
presented in a by-subject listing. 
11.
Pharmacokinetics
Plasma levels of circulating roflumilast and its major N-oxide metabolite will be 
measured at the following time points: 
All enrolled subjects will have a trough PK sample at the Week 4 visit. 
A subset of 6 subjects who consent will have an additional PK sample collected 
pre-dose at the Week 2 visit. 


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PK concentration will be summarized by nominal time point. In addition, PK parameters 
and concentration listing will be presented as well. A detailed description of the PK 
analysis will be presented in a separate pharmacokinetics report. 
12.
Planned Tables, Figures, and Listings
A table of contents for the tables, listings, and figures will be presented in a separate 
document as the list of summaries or numbering may change after finalization of this 
document. If additional summaries are added that are not described in this document, 
then this SAP will be amended, or an addendum will be created.