Clinical trial NCT04053387
Conditions: Plaque Psoriasis
Keywords: Tapinarof plaque psoriasis, adult phase 3 topical open-label efficacy safety psoriasis long-term therapeutic aryl hydrocarbon receptor modulating agent
Sponsor: Organon and Co
Start date: 2019-08-13; Completion date: 2021-04-06
Enrollment: 763 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in adults with plaque psoriasis. Subjects in this study completed treatment in 1 of 2 Phase 3 pivotal efficacy and safety studies (Study DMVT-505-3001 or Study DMVT-505-3002). This study will consist of up to 40 weeks of treatment and a 4-week safety follow-up period.

Detailed description:
At the completion of the Week-12 visit of the pivotal study (Baseline \[Day 1\] in this study), all eligible subjects will be offered enrollment in the long-term extension study. Study visits during the treatment period for all subjects will occur every 4 weeks (± 3 days). The total duration of study participation will be approximately 44 weeks.

Arms: arm 1: Subjects who completed 1 of the phase 3 studies evaluating the safety and efficacy of tapinarof had the option to enter this extension study.

Subjects entering with a PGA ≥ 1 received treatment with tapinarof cream, 1% until they achieve a PGA = 0, at which time treatment was discontinued and subjects were monitored for durability of response (remittive response). If/when disease worsening occurred, as evidenced by a PGA ≥ 2, treatment was re initiated and continued until a PGA = 0 was achieved.

Subjects entering with a PGA = 0 had treatment discontinued and were monitored for duration of remittive response. If/when disease worsening occurred, as evidenced by a PGA ≥ 2, treatment was re initiated and continued until a PGA = 0 was achieved.

This treatment and re treatment pattern of use was continued until the end of the study
Interventions: intervention 1: tapinarof cream, 1%
Intervention descriptions: intervention 1: Intermittent use of Tapinarof cream, 1%, applied once daily according to PGA score

Protocol documents:
Prot_000.pdf: 
Tapinarof
DMVT-505-3003
Dermavant Sciences GmbH
Clinical Study Protocol 
Confidential
Page 1
CLINICAL STUDY PROTOCOL
Title
A Long-Term, Open-Label, Extension Study to Evaluate the Safety 
and Efficacy of Tapinarof Cream, 1% for the Treatment of Plaque 
Psoriasis in Adults
Sponsor
Dermavant Sciences GmbH
Viaduktstrasse 8
4051 Basel, Switzerland
Compound Name
DMVT-505 (tapinarof)
Protocol Number
DMVT-505-3003
Indication
Plaque Psoriasis
Development Phase
3
IND Number
104601
Version/
Effective Date:
Original Protocol                           30-JANUARY-2019
Amendment 1 (Version 1.0)          16-DEC-2019
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SPONSOR SIGNATURE PAGE 
 
Study Title: A Long-Term, Open-Label, Extension Study to Evaluate the Safety and Efficacy of 
Tapinarof Cream, 1% for the Treatment of Plaque Psoriasis in Adults  
Protocol Number: DMVT-505-3003 
 
This protocol has been approved by a representative of Dermavant Sciences, Inc. The following 
signature documents this approval. 
 
 
 
 
 
 
 
 
 
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DMVT-505-3003 
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MEDICAL MONITOR/SPONSOR INFORMATION PAGE 
Medical Monitor/serious adverse event (SAE) Contact Information 
 
Study Sponsor 
This study is sponsored by Dermavant Sciences GmbH 
Dermavant Sciences GmbH Registered Address 
Dermavant Sciences GmbH 
Viaduktstrasse 8 
4051 Basel, Switzerland 
United States Agent and Regulatory Contact  
Dermavant Sciences, Inc. 
359 Blackwell St., Suite 240 
Durham, NC 27701 
USA 
 
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INVESTIGATOR STATEMENT 
Study Title: A Long-Term, Open-Label, Extension Study to Evaluate the Safety and Efficacy of 
Tapinarof Cream, 1% for the Treatment of Plaque Psoriasis in Adults 
x I confirm agreement to conduct the study in compliance with the protocol. 
x I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study. 
x I agree to ensure that all associates, colleagues, and employees assisting in the 
conduct of the study are informed about their obligations and comply with the study 
protocol. Mechanisms are in place to ensure that site staff receives the appropriate 
information throughout the study. 
 
 
 
 
 
Principal Investigator Name (Printed) 
 
Signature 
 
 
 
Date 
 
Site 
 
 
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DMVT-505-3003 
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Clinical Study Protocol  
 
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TABLE OF CONTENTS 
ABBREVIATIONS .......................................................................................................................10 
SYNOPSIS ....................................................................................................................................12 
SCHEDULE OF ASSESSMENTS ................................................................................................16 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Background Information and Study Rationale ...........................................................19 
1.1.1. 
Background Information .............................................................................................19 
1.1.2. 
Study Rationale ...........................................................................................................21 
1.2. 
Rationale for Study Design and Dose .........................................................................21 
1.3. 
Potential Risks and Benefits .......................................................................................21 
1.3.1. 
Risk Assessment .........................................................................................................21 
1.3.1.1. 
Dermatological Adverse Events, Including Skin Irritation or Allergic 
Reaction ......................................................................................................................21 
1.3.1.2. 
Systemic Adverse Events ...........................................................................................22 
1.3.1.3. 
Reproductive and Developmental Toxicity ................................................................22 
1.3.2. 
Benefit Assessment .....................................................................................................23 
1.3.3. 
Overall Benefit/Risk ...................................................................................................23 
2. 
OBJECTIVES AND ENDPOINTS ............................................................................24 
3. 
STUDY DESIGN .......................................................................................................25 
3.1. 
Overall Design ............................................................................................................25 
3.2. 
Treatment Groups and Duration .................................................................................26 
4. 
STUDY POPULATION .............................................................................................27 
4.1. 
Type and Number of Subjects ....................................................................................27 
4.2. 
Inclusion Criteria ........................................................................................................27 
4.3. 
Exclusion Criteria .......................................................................................................28 
4.4. 
Lifestyle Restrictions ..................................................................................................28 
4.5. 
Screening Failure ........................................................................................................28 
4.6. 
Withdrawal Criteria ....................................................................................................28 
4.6.1. 
Reasons for Withdrawal from Study ..........................................................................29 
4.6.2. 
Temporary Discontinuation ........................................................................................29 
4.6.3. 
Withdrawal Procedures ...............................................................................................29 
4.7. 
Lost to Follow-up .......................................................................................................30 
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5. 
STUDY TREATMENT ..............................................................................................31 
5.1. 
Study Drug ..................................................................................................................31 
5.1.1. 
Description, Packaging, and Labeling ........................................................................31 
5.1.2. 
Storage ........................................................................................................................31 
5.1.3. 
Handling and Disposal ................................................................................................31 
5.1.4. 
Preparation ..................................................................................................................32 
5.1.5. 
Administration of Study Drug ....................................................................................32 
5.1.5.1. 
Treatment by Physician Global Assessment Score ....................................................32 
5.1.5.2. 
Disease Worsening (Physician Global Assessment Score ≥ 2) During the 
Study ...........................................................................................................................32 
5.1.5.3. 
Application of Study Drug ..........................................................................................33 
5.2. 
Randomization/Treatment Assignment ......................................................................34 
5.3. 
Blinding ......................................................................................................................34 
5.4. 
Compliance with Study Drug Administration ............................................................34 
5.5. 
Treatment after the End of the Study ..........................................................................34 
5.6. 
Prior and Concomitant Therapy ..................................................................................35 
5.6.1. 
Permitted Medications and Nondrug Therapies .........................................................35 
5.6.2. 
Prohibited Medications and Nondrug Therapies ........................................................35 
6. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................36 
6.1. 
Medical History and Demography..............................................................................36 
6.1.1. 
Medical History ..........................................................................................................36 
6.1.2. 
Demographics .............................................................................................................36 
6.2. 
Efficacy Assessments .................................................................................................36 
6.2.1. 
Assessments by Investigator .......................................................................................36 
6.2.1.1. 
Physician Global Assessment .....................................................................................36 
6.2.1.2. 
Body Surface Area ......................................................................................................37 
6.2.1.3. 
Psoriasis Area and Severity Index ..............................................................................37 
6.2.2. 
Assessments Completed by Subject ...........................................................................37 
6.2.2.1. 
Dermatology Life-Quality Index ................................................................................37 
6.2.2.2. 
Patient Satisfaction Questionnaire ..............................................................................37 
6.2.3. 
Optional Clinical Photography ...................................................................................37 
6.3. 
Safety Assessments .....................................................................................................38 
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6.3.1. 
Adverse Events ...........................................................................................................38 
6.3.2. 
Brief Physical Examination ........................................................................................38 
6.3.3. 
Vital Signs ..................................................................................................................38 
6.3.4. 
Clinical Safety Laboratory Assessments ....................................................................38 
6.3.5. 
Local Tolerability Scale ..............................................................................................40 
6.4. 
Treatment of Study Drug Overdose ............................................................................40 
6.5. 
Pharmacokinetics/Pharmacodynamics .......................................................................40 
7. 
TIMING OF PROCEDURES AND ASSESSMENTS ..............................................41 
7.1. 
Visit 1; Baseline ..........................................................................................................41 
7.2. 
Visits 2 to 10; Treatment Period .................................................................................42 
7.3. 
Visit 11; ......................................................................................................................42 
7.4. 
Follow-up Visit ...........................................................................................................43 
7.5. 
Phone Contact at Week 2 (Day 15 ±3 Days) ..............................................................44 
7.6. 
Unscheduled Visits .....................................................................................................44 
7.7. 
Early Termination .......................................................................................................44 
7.8. 
End of Study ...............................................................................................................45 
8. 
SAFETY MONITORING AND REPORTING .........................................................46 
8.1. 
Adverse Events, Serious Adverse Events, and Adverse events of Special 
Interest ........................................................................................................................46 
8.1.1. 
Definition of Adverse Events .....................................................................................46 
8.1.2. 
Definition of Serious Adverse Event ..........................................................................47 
8.1.3. 
Adverse Events of Special Interest .............................................................................48 
8.2. 
Classification of Adverse Events ................................................................................48 
8.2.1. 
Assigning Severity Rating for Adverse Events ..........................................................48 
8.2.1.1. 
Criteria for Determining Adverse Event Severity ......................................................48 
8.2.1.2. 
Toxicity Management Criteria ....................................................................................49 
8.2.2. 
Assigning Causal Relationship to Study Drug ...........................................................50 
8.3. 
Time Period and Frequency for Event Assessment and Follow-up ...........................50 
8.3.1. 
Adverse Event Reporting ............................................................................................50 
8.3.2. 
Follow-up of Adverse Events .....................................................................................51 
8.4. 
Reporting Procedures ..................................................................................................51 
8.4.1. 
Serious Adverse Event Reporting ...............................................................................51 
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8.4.2. 
Regulatory Reporting Requirements for Serious Adverse Events .............................51 
8.5. 
Pregnancy Management and Reporting ......................................................................52 
8.6. 
Safety Oversight .........................................................................................................52 
9. 
DATA MANAGEMENT ...........................................................................................53 
10. 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES ............................54 
10.1. 
General Considerations ...............................................................................................54 
10.2. 
Determination of Sample Size ....................................................................................54 
10.3. 
Analysis Populations ..................................................................................................54 
10.4. 
Planned Analyses ........................................................................................................54 
10.4.1. 
Demographics and Baseline Characteristics ...............................................................54 
10.4.2. 
Efficacy Analyses .......................................................................................................54 
10.4.3. 
Safety Analyses ..........................................................................................................55 
10.4.4. 
Analysis of Functional Outcomes and Quality of Life Endpoints ..............................55 
10.4.5. 
Analysis of Patient Satisfaction Questionnaire ...........................................................56 
10.5. 
Interim Analyses .........................................................................................................56 
10.6. 
Handling of Missing Data ...........................................................................................56 
11. 
RESPONSIBILITIES .................................................................................................57 
11.1. 
Investigator Responsibilities .......................................................................................57 
11.1.1. 
Good Clinical Practice ................................................................................................57 
11.1.2. 
Institutional Review Board/Independent Ethics Committee Approval ......................57 
11.1.3. 
Informed Consent/Assent ...........................................................................................57 
11.1.4. 
Confidentiality ............................................................................................................58 
11.1.5. 
Study Files and Retention of Records ........................................................................58 
11.1.6. 
Electronic Case Report Forms ....................................................................................59 
11.1.7. 
Drug Accountability ...................................................................................................59 
11.1.8. 
Inspections ..................................................................................................................60 
11.1.9. 
Protocol Compliance ..................................................................................................60 
11.2. 
Sponsor Responsibilities .............................................................................................60 
11.2.1. 
Protocol Modifications ...............................................................................................60 
11.2.2. 
Study Report and Publications....................................................................................60 
11.2.3. 
Posting of Information on Publicly Available Clinical Trial Registers ......................61 
11.3. 
Joint Investigator/Sponsor Responsibilities ................................................................61 
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11.3.1.
Access to Information for Monitoring........................................................................61
11.3.2.
Access to Information for Auditing or Inspections ....................................................61
11.3.3.
Study Discontinuation ................................................................................................61
12.
REFERENCES ...........................................................................................................62
13.
APPENDICES ............................................................................................................63
Physician Global Assessment................................................................................63
Calculation of Percent Body Surface Area (%BSA) Affected and 
Psoriasis Area Severity Index (PASI).........................................................................64
Dermatology Life Quality Index (DLQI) Ages 16 and up ....................................66
Local Tolerability Scale Assessment.....................................................................67
Patient Satisfaction Questionnaire.........................................................................68
Protocol Amendment Summary of Changes .........................................................70
LIST OF TABLES
Table 1:
Schedule of Assessments............................................................................................16
Table 2
Tapinarof Cream.........................................................................................................31
Table 3:
Laboratory Tests .........................................................................................................39
Table 4:
Criteria for Determining the Grade/Severity of Adverse Event Terms Not 
Specified by the National Cancer Institute CTCAE...................................................49
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ABBREVIATIONS 
Term 
Description 
AD 
atopic dermatitis 
AE 
adverse event 
AESI 
adverse event of special interest 
AhR 
aryl hydrocarbon receptor 
ALT 
alanine aminotransferase 
Anti-HBc 
anti-hepatitis B core antigen 
AST 
aspartate aminotransferase 
BP 
blood pressure 
BSA 
body surface area 
BUN 
blood urea nitrogen 
BWTP 
Beijing Wenfeng Tianji Pharmaceuticals  
C 
collect 
CBP 
childbearing potential 
CFR 
Code of Federal Regulations 
CTCAE 
Common Terminology Criteria for Adverse Events 
D 
dispense 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic case report form 
ET 
early termination 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone 
F-U 
follow-up 
GSK 
GlaxoSmithKline 
HBsAg 
hepatitis B surface antigen 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
IV 
intravenous 
LOCF 
Last Observation Carried Forward 
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Term 
Description 
LTS 
Local Tolerability Scale 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MedDRA 
Medical Dictionary for Regulatory Activities 
MCV 
mean corpuscular volume 
MSDS 
Material Safety Data Sheet 
Nrf2 
nuclear factor-erythroid 2-related factor-2 
OC 
Observed Cases 
PASI 
Psoriasis Area and Severity Index 
PGA 
Physician Global Assessment 
PK 
pharmacokinetic 
PND 
postnatal day 
RBC 
red blood cells 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
TAMA 
therapeutic AhR-modulating agent 
TEAE 
treatment-emergent adverse event 
UNSCH 
unscheduled 
US; USA 
United States (of America) 
UV 
ultraviolet 
WBC 
white blood cells 
WHO 
World Health Organization  
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SYNOPSIS 
Name of Sponsor/Company: 
Dermavant Sciences GmbH 
Name of Investigational Product: 
DMVT-505 (tapinarof cream, 1%) 
Name of Active Ingredient: 
Tapinarof 
Protocol Number: DVT-505-3003 
Phase: 
3 
Country: US and Canada 
Title of Study: 
A Long-Term, Open-Label, Extension Study to Evaluate the Safety and Efficacy of Tapinarof Cream, 1% for the 
Treatment of Plaque Psoriasis in Adults 
Study Centers:  
Approximately 100 to 120 sites in the United States (US) and Canada  
Objectives: 
x 
To evaluate the safety and tolerability of tapinarof cream, 1% in adults with plaque psoriasis 
x 
To describe the efficacy of tapinarof cream, 1% over an extended period of time in adults with plaque 
psoriasis 
x 
To describe the effect of tapinarof cream, 1% on psoriasis symptom severity and the associated impact on 
daily activities and attitudes in adults with plaque psoriasis 
Methodology:  
This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical tapinarof 
cream, 1% in adults with plaque psoriasis.  Subjects in this study completed treatment with tapinarof in 1 of 2 
Phase 3 pivotal efficacy and safety studies (Study DMVT-505-3001 or Study DMVT-505-3002).  This study will 
consist of up to 40 weeks of treatment and a 4-week safety follow-up period. 
At the completion of the Week-12 visit of the pivotal study (Baseline [Day 1] in this study), all eligible subjects 
will be offered enrollment in the long-term extension study.  Study visits during the treatment period for all 
subjects will occur every 4 weeks (± 3 days).  Unscheduled visits may occur, as needed.  Subjects who withdraw 
from the study before Week 40 will return to the study center for an Early Termination visit.  The total duration of 
study participation will be approximately 44 weeks. 
Subjects in the study will be treated based on their PGA score from the Week 12 visit in the pivotal study. Subjects 
entering with a PGA ≥ 1 will receive treatment with tapinarof cream, 1% until they achieve a PGA score of 0, at 
which time treatment will be discontinued and subjects monitored for durability of response. If disease worsening 
occurs, as evidenced by a PGA ≥ 2, treatment will then be re-initiated and continued until a PGA of 0 is observed. 
Subjects entering with a PGA of 0 will have treatment discontinued and be monitored for durability of response. If 
disease worsening occurs, as evidenced by a PGA ≥ 2, then treatment will be re-initiated and continued until a 
PGA of 0 is observed.   This treatment and re-treatment pattern of use will be continued until the end of the study 
(i.e., subjects may receive study treatment up until the Week 40 visit). 
Study drug will be dispensed to subjects during the study visits and will be administered at home between study 
visits as instructed by site personnel.  Subjects will be instructed to apply study drug once daily to all affected 
areas, including newly appearing lesions and lesions or affected areas that improve during the study.  Subjects will 
apply sufficient study drug to cover completely each lesion with a thin layer of study drug and will record the time 
of study drug application in a daily diary provided by the study site.  (Note that subjects are allowed, but not 
required, to treat fingernails, toenails, palms, soles and scalp lesions with study drug; however, efficacy analyses 
will not include assessment of improvement of psoriasis in these areas).  Subjects will be instructed to maintain the 
approximate dosing time chosen at the beginning of the study for their full study participation.  Study drug 
application instructions will be reviewed at subsequent study visits.  During subsequent study visits, subjects will 
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apply the daily dose of study drug while at the site, under the supervision of site personnel, after efficacy and 
safety assessments have been completed, if applicable.  The time of the study drug application and assessments 
will depend on the time of the study visit (either morning or afternoon visit).  Therefore, the timing of the study 
visit may lead to a change from the subject’s chosen dosing time; if this occurs, it will NOT be considered a 
protocol deviation; the subject should resume their chosen dosing time the day following any such study visit 
study drug application. This should only occur for subjects receiving study treatment.   
Rescue medications may be initiated with consultation of the medical monitor. 
Sample Size Justification: 
The sample size of this study is based on the International Conference on Harmonisation (ICH) E1 guideline on 
extent of population exposure to assess clinical safety for drugs intended for long-term treatment of 
non-life-threatening conditions.  An estimated 850 subjects who complete Study DMVT-505-3001 or 
Study DMVT-505-3002 will be enrolled in this study across all regions.  A high discontinuation rate is 
anticipated in this long-term extension study.  Approximately 300 subjects are expected to complete the study 
(up to 40 weeks of treatment). 
Number of Subjects (planned):  
Approximately 850 subjects ages 18 to 75 years of age 
Diagnosis and Main Criteria for Inclusion:  
Inclusion criteria: 
1. Completed the 12-week treatment period in 1 of the 2 pivotal studies (Study DMVT-505-3001 or 
Study DMVT-505-3002); 
2. Male or female; 
3. Female subjects of childbearing potential and male subjects who are engaging in sexual activity that 
could lead to pregnancy should use one of the following acceptable birth control methods while on study 
and for 4 weeks after the last exposure to study drug.  Acceptable contraception methods are: 
x 
Female subject or male subject’s female partner is surgically sterile (bilateral tubal ligation, 
hysterectomy, bilateral oophorectomy) for a minimum of 3 months prior to the first dose of study 
drug 
x 
Female subject or male subject’s female partner has had an intrauterine device in place for at least 3 
months prior to the first dose of study drug 
x 
Double barrier methods (e.g., condom plus diaphragm, condom or diaphragm plus spermicide) 
starting at least 14 days prior to the first dose of study drug 
x 
Subjects who claim abstinence as their method of contraception are allowed provided they agree to 
use a double barrier method (e.g., condom plus diaphragm, condom or diaphragm plus spermicide) 
should they become sexually active from Screening to 1 month after the last dose of study drug 
x 
Surgical sterilization of male subject or female subject’s male partner (vasectomy) a minimum of 3 
months prior to first dose of study drug 
x 
Female subject or male subject’s female partner is taking hormonal contraceptives starting at least 3 
months prior to the first dose of study drug. If hormonal contraceptives were started less than 3 
months prior to the first dose of study drug, subjects must agree to use a double barrier method (e.g., 
condom plus diaphragm, condom or diaphragm plus spermicide) from Screening through 3 months 
after the initiation of hormonal contraceptives. 
 
These allowed methods of contraception are only effective when used consistently, correctly and in 
accordance with the product label.  The Investigator is responsible for ensuring that subjects 
understand how to properly use these methods of contraception. Non-CBP is defined as premenarchal 
or premenopausal females with a documented bilateral tubal ligation, bilateral oophorectomy (removal 
of the ovaries) or hysterectomy, or hysteroscopic sterilization; or postmenopausal females defined as a 
cessation of menses for at least 12 months without an alternative medical cause.  In questionable cases 
a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 ml/U is confirmatory.  
Documented verbal history from the subject is acceptable.   
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x 
Change and percent change from baseline in %BSA affected by visit (OC and LOCF) 
x 
Change and percent change in PASI score by visit (OC and LOCF) 
x 
Change in disease impact on daily activities, as measured by the DLQI total and individual dimension 
scores 
Statistical Methods: 
All study data will be summarized overall and by treatment group in the pivotal studies using descriptive statistics 
using the intent-to-treat (ITT) analysis set of subjects.  Categorical variables will be reported using frequency and 
percentage (e.g., sex, race).  Continuous variables will be reported using number of subjects, mean, standard 
deviation (SD), median, minimum, and maximum.  All safety and efficacy data will be listed by subject. 
Demographics, baseline characteristics, and all safety assessments (including LTS assessments), will be analyzed 
using descriptive statistics.  The Kaplan-Meier product limit method will be used to estimate the median time 
(if estimable) from baseline to first disease worsening and first treatment success.  If the median is not estimable 
(e.g., < 50% of subjects worsen), other methods for estimating the median and/or other percentiles of worsening 
will be applied.  All other efficacy assessments will be analyzed using descriptive statistics. 
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SCHEDULE OF ASSESSMENTS 
Table 1: 
Schedule of Assessments 
 
Visit 1 
Long-term Extension Period 
Procedures and 
Assessment 
Phone 
Call 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 Visit 10 Visit 11 Visit 12 Other Visits 
Base- 
linea 
Day 1 
Week 2 
Day  
15 
Week 4 
Day 
29 
Week 8 
Day 
57 
Week 12 
Day 
85 
Week 16 
Day 
113 
Week 20 
Day 
141 
Week 24 
Day 
169 
Week 28 
Day 
197 
Week 32 
Day 
225 
Week 36 
Day 
253 
Week 40 
Day 
281 
Week 44 
(F-U) 
Day 
309 
UNSCHb ETc 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics/ 
Medical History 
Xd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical 
examination 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
(pulse, BP, temperature)e 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test 
(all females of CBP) 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
As 
needed 
X 
Clinical laboratory testsf 
[X] 
 
X 
 
X 
 
 
 
 
 
 
X 
X 
As 
needed 
X 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
X 
X 
As 
needed 
X 
Photography, if 
applicableg 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigator assessed:e 
PGA 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BSA affectedh 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PASI 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
LTSi 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
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DMVT-505-3003 
Dermavant Sciences GmbH 
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Visit 1 
Long-term Extension Period 
Procedures and 
Assessment 
Phone 
Call 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 Visit 10 Visit 11 Visit 12 Other Visits 
Base- 
linea 
Day 1 
Week 2 
Day  
15 
Week 4 
Day 
29 
Week 8 
Day 
57 
Week 12 
Day 
85 
Week 16 
Day 
113 
Week 20 
Day 
141 
Week 24 
Day 
169 
Week 28 
Day 
197 
Week 32 
Day 
225 
Week 36 
Day 
253 
Week 40 
Day 
281 
Week 44 
(F-U) 
Day 
309 
UNSCHb ETc 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
±3 
Days 
Completed by subject:e 
DLQI 
[X] 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
LTSi 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Patient Satisfaction 
Questionnaire 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense/collect diaryj 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Review diaries for 
treatment compliance 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Dispense/collect 
study drugk 
D 
 
C/D 
C/D 
C/D 
C/D 
C/D 
C/D 
C/D 
C/D 
C/D 
C 
 
As 
needed 
C 
Review instructions for 
study drug applicationl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
As 
needed 
 
Study drug application 
under supervisionm 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X 
 
BP = blood pressure; BSA = body surface area; C = collect; CBP = child-bearing potential; D = dispense; DLQI = Dermatology Life Quality Index; ET = early 
termination; F-U = follow-up; LTS = Local Tolerability Scale; PASI = Psoriasis Area and Severity Index; PGA = Physician Global Assessment; 
UNSCH = unscheduled. 
a Visit to occur at the time of completion of Visit 6 (Week 12) in pivotal study. The last assessment completed as part of the pivotal study will be used as the 
baseline value for assessments with a bracketed “X.” 
b Subjects who experience disease worsening (PGA ≥2) between scheduled study visits may contact the study site to arrange an unscheduled visit (see 
Section 5.1.5.1). If disease worsening is confirmed, a new treatment course will be initiated. 
c Subjects who withdraw from the study before Week 40 will complete an ET visit. 
d As collected at Screening/Baseline in pivotal study. 
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Clinical Study Protocol  
 
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e Performed prior to study drug application on study visit days. 
f Serum chemistry (including liver chemistry tests) and hematology. 
g Photography will be performed in a subgroup of subjects at selected (approximately 20) study centers; this is not required of subjects for participation in the 
study. Informed consent and photographic release will be required. 
h %BSA affected must be performed before PASI. (Note that subjects are allowed, but not required, to treat fingernails, toenails, palms, soles, and scalp lesions 
with study drug; however, efficacy analyses will not include assessment of improvement of psoriasis in these areas 
i The LTS assessment is only required to be completed if the subject was applying study drug for the period before the current visit. 
j Study diary should only be dispensed if study product is dispensed. 
k Subjects will be monitored for disease worsening (PGA ≥2), and study drug administration may be started at any time during the observation period (see 
Section 5.1.5.1) 
l Subjects will be instructed to apply study drug once daily at the approximate same time each day, based on subject preference. This should only occur for 
subjects receiving study treatment. 
m Study drug will be applied after safety assessments have been conducted, . Subjects will be instructed and reminded on how to apply study drug at each visit, 
except during the final treatment visit (see Section 5.1.5.3 for additional details on timing of study drug application during study visits). This should only occur 
for subjects receiving study treatment. 
 
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Clinical Study Protocol  
 
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1. 
INTRODUCTION 
1.1. 
Background Information and Study Rationale 
1.1.1. 
Background Information 
Psoriasis is a common, chronic relapsing inflammatory skin disease [Parisi, 2012] with recurrent 
episodes of prominently erythematous and scaly patches (plaques). Approximately 2% to 3% of 
the global population is affected by psoriasis; those affected are predominantly adults, who are 
most often diagnosed between the ages of 18 to 35 years. Psoriasis disrupts daily activities such 
as work and/or school attendance, interpersonal relationships, recreational activities, and 
intimacy – thereby significantly impacting sufferers’ quality of life. Furthermore, psoriasis 
sufferers can also have co-morbidities such as arthritis, depression, inflammatory bowel disease, 
and cardiovascular diseases. 
Up to 80% of patients have mild to moderate plaque-type psoriasis, which is generally managed 
with topical treatments. The most commonly used treatments for psoriasis include topically 
applied corticosteroids and Vitamin D analogs, alone or in combination. Vitamin D analogs are 
moderately efficacious as monotherapy, while application of topical corticosteroids – particularly 
the very potent ones – is restricted in terms of body areas that can be treated and the duration of 
use due to the well-known application site and systemic adverse drug reactions [Mason, 2013]. 
Although numerous topical treatment options are available, there remains a need for a topical 
treatment that combines a high level of efficacy with an acceptable safety profile that permits 
application to a large body surface area (BSA) without restrictions on duration of treatment. 
DMVT-505 (tapinarof), formerly known as GSK2894512, is a fully synthetic hydroxylated 
stilbene that is being developed by Dermavant Sciences GmbH (Dermavant) as a novel 
anti-inflammatory agent for the topical treatment of atopic dermatitis (AD) and plaque psoriasis. 
The compound (number WBI-1001) was initially developed by Welichem Biotech Inc. 
(Welichem; Burnaby, British Columbia, Canada) and then was acquired by GlaxoSmithKline 
(GSK) on 31 July 2012 for further development in the rest of the world except China. Beijing 
Wenfeng Tianji Pharmaceuticals (BWTP) is developing a compound in China identified as 
Benvitimod (active ingredient corresponds to tapinarof) with a unique topical formulation. 
Dermavant acquired the drug from GSK on 20 August 2018 for continued development. 
Tapinarof cream, 1% is a white to off-white, oil-in-water emulsion intended for topical 
application to AD and psoriatic skin lesions, which has a novel mechanism of action. The drug 
likely mediates its effects via the aryl hydrocarbon receptor (AhR) agonist and nuclear 
factor-erythroid 2-related factor-2 (Nrf2) because the pattern of pro-inflammatory mediators 
inhibited by tapinarof is different from that of corticosteroids, calcineurin inhibitors, vitamin D 
analogs, and other immunosuppressive agents commonly used to treat AD and psoriasis. Rather, 
the profile of biological responses elicited by tapinarof most closely matches that of the dual 
activation properties of coal tar, a common nonprescription treatment for psoriasis. Together, 
existing data identify tapinarof as a non-steroid, therapeutic AhR-modulating agent (TAMA), 
which is a unique mechanism of action compared with existing therapies. 
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Tapinarof cream has been evaluated in nonclinical studies at concentrations up to 8% and in 
clinical studies at concentrations up to 2%. Three Phase I clinical pharmacology studies in 
healthy volunteers and 7 Phase I/II studies in subjects with AD and psoriasis have been 
completed. Refer to the current version of the tapinarof Investigator’s Brochure for detailed 
information. Tapinarof has demonstrated an acceptable safety profile and a clear therapeutic 
effect, as compared to vehicle, in both psoriasis and AD. 
Four randomized, double-blind, vehicle-controlled, clinical studies to evaluate the safety and 
efficacy of topically-applied tapinarof cream in subjects with AD or psoriasis were conducted by 
Welichem; one 28-day and one 12-week study was completed for each indication. 
These studies enrolled a total of 282 adult subjects, with 235 subjects exposed to tapinarof cream 
0.5%, 1%, or 2% (Formulation C) once or twice daily for a period of 28 to 84 days. Efficacy was 
rapid, and statistically significant differences versus vehicle were observed as early as Day 14 for 
the majority of efficacy parameters in both indications. The most frequently reported (1 to 6% of 
235 subjects) dermatological adverse events (AEs), regardless of causality, were application site 
discoloration/hyperpigmentation, application site dermatitis, papular rash, pruritus, dermatitis 
contact, folliculitis, erythema, and skin burning sensation. Nasopharyngitis and headache were 
the most frequently-reported (>10% of subjects) nondermatological AEs overall. Overall, results 
of the clinical studies indicated tapinarof was highly efficacious for both AD and psoriasis, with 
a favorable safety profile. 
The first clinical study with Formulation F (Study 201851) was a Phase 1 study to evaluate 
the systemic exposure and pharmacokinetic (PK) parameters of tapinarof cream, 1% and 2%. 
This study was conducted in 11 subjects with AD; 5 subjects were treated with the 2% dose and 
6 subjects were treated with the 1% dose. Headache was the most frequently reported (100% and 
60% of subjects at the 1% and 2% doses, respectively) nondermatological adverse event. 
Two Phase 2b, 12-week, randomized, double-blind, vehicle-controlled, 6-arm, parallel-group, 
dose-finding studies with topically applied tapinarof cream were conducted by GSK; 1 study 
each in subjects with AD or psoriasis. These 2 studies evaluated the safety and efficacy of 
tapinarof cream (Formulation F) at 2 concentrations (0.5% or 1%) and 2 application frequencies 
(once daily or twice daily) in 247 adult and adolescent subjects with AD and in 227 adult 
subjects with plaque psoriasis. 
In both studies, tapinarof showed a clear therapeutic effect compared with vehicle, with the 
1% concentration treatment groups demonstrating a higher proportion of subjects with treatment 
success compared with the 0.5% concentration groups (applied once daily and twice daily in the 
AD study). In both indications, the tapinarof 1% dosing groups showed a faster onset of action 
than the 0.5% dosing groups, and once daily application had similar efficacy to twice daily 
application. In both Phase 2b studies, tapinarof showed an acceptable safety profile. Treatment-
emergent adverse events (TEAEs) were reported with a higher frequency in the tapinarof groups 
than in the vehicle groups. The most frequent TEAEs (≥5% in any arm or in total) were 
nasopharyngitis, folliculitis, dermatitis contact, atopic dermatitis, upper respiratory tract 
infection, headache, vomiting, acne, application site dermatitis, miliaria, dermatitis allergic, and 
impetigo. The majority of TEAEs were mild or moderate in severity. In each study, the 
tapinarof 1% once daily treatment group had a lower frequency of TEAEs than the tapinarof 1% 
twice daily treatment group. 
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1.1.2. 
Study Rationale 
This 40-week, Phase 3, open-label extension study is being conducted as part of a clinical 
development program to evaluate the long-term safety and continued efficacy of tapinarof cream, 
1% for the topical treatment of plaque psoriasis in adults with psoriasis.  Subjects in this study 
will be selected from those subjects who complete 1 of 2 Phase 3 pivotal efficacy and safety 
studies (pivotal Study DMVT-505-3001 or pivotal Study DMVT-505-3002) and meet the 
predefined criteria to enroll into this study. 
1.2. 
Rationale for Study Design and Dose 
As in the pivotal studies, this Phase 3 study continued to be conducted at multiple study centers 
in more than 1 country to enhance the possibility of inclusion of a wider range of population 
groups and to subsequently increase generalizability of the results. Tapinarof cream is intended 
for long-term, intermittent use in non-life-threatening inflammatory dermatologic conditions. 
Therefore, the 40-week duration of long-term, intermittent use of tapinarof in this study, in 
addition to the treatment received in the pivotal study, is expected to be an adequate duration to 
assess safety and efficacy of repeated treatment courses of tapinarof as recommended in the 
International Conference on Harmonisation E1 (ICH E1) guideline on the extent of population 
exposure to assess clinical safety for drugs intended for long-term treatment of non-life-
threatening conditions [ICH, 1994], which recommends a minimum of 100 subjects be treated 
with the intended clinical dose and to be followed for AEs over at least 1 year. 
The once daily topical application of tapinarof cream, 1% concentration administered in the 
pivotal studies will be continued in this open-label extension study. 
1.3. 
Potential Risks and Benefits 
To assess any potential impact on subject eligibility with regard to safety, the Investigator must 
refer to the current version of the tapinarof Investigator’s Brochure for detailed information 
regarding warnings, precautions, contraindications, AEs, and other significant data pertaining to 
the study drug being used in this study. 
1.3.1. 
Risk Assessment 
1.3.1.1. 
Dermatological Adverse Events, Including Skin Irritation or Allergic Reaction 
Tapinarof or its excipients may induce skin irritation. Allergic or irritant reactions in the exposed 
areas may present as erythema, edema, papules, or vesicles. In the event of pronounced skin 
reaction, spreading of the eczematous reaction beyond the original application site(s) and/or 
more generalized (remote) skin reactions may be observed. 
In the dose-ranging study 203120 in psoriasis, the most frequently reported dermatologic AEs 
were folliculitis and contact dermatitis. In the dose-ranging study 203121 in AD, the most 
frequently reported dermatologic AEs were folliculitis and AD. Nonclinical dermal toxicity 
studies of up to 8% tapinarof for up to 13 weeks indicated local effects are primarily mild to 
moderate skin irritation that is reversible; tapinarof did not show evidence of sensitization. In 
initial clinical studies using a different formulation of tapinarof (Formulation C), AEs of skin 
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hyperpigmentation, application site dermatitis, papular rash, pruritus, contact dermatitis, 
folliculitis, erythema, and skin burning sensation were reported. 
To mitigate these potential risks, subjects with a known or suspected intolerance to tapinarof or 
its excipients will be excluded from enrollment. Subjects’ skin will be evaluated routinely for 
signs of irritation or allergic reaction, and if needed, study treatment will be interrupted and an 
appropriate treatment provided. Note that after cessation of exposure, dermatological reactions 
generally subside spontaneously or with topical treatments. 
1.3.1.2. 
Systemic Adverse Events 
Nasopharyngitis and headache were the most frequently reported nondermatological AEs in 
dose-ranging Study 203120 in psoriasis. In dose-ranging Study 203121 in AD, the most 
frequently reported nondermatological AEs were nasopharyngitis, upper respiratory tract 
infection, and headache. In the initial clinical studies (in AD and psoriasis) using a different 
tapinarof formulation (Formulation C), nasopharyngitis and headache were the most frequently 
reported nondermatological AEs. In the open-label PK Study 201851 with BID dosing of 
Formulation F of tapinarof cream (n=11), 1% and 2%, headache was the most frequently 
reported AE during the study (reported for 100% and 60% of subjects at the 1% and 2% doses, 
respectively). 
In a nonclinical study in minipigs using intravenous (IV) administration, reversible decreases in 
arterial blood pressure and PR interval were observed; however, in this study and repeat dermal 
toxicity studies, there were no effects on QT interval or heart rate. Repeat-dose dermal toxicity 
studies also showed findings related to the liver (increased weights and hepatocellular 
hypertrophy/regeneration) and thymus (thymic cortex depletion in adult rabbits and rats; changes 
in thymus weight, microscopic decreased cellularity, and changes in thymic T cell maturation in 
juvenile rats) with associated secondary hematological findings. Thymic findings were also 
noted in repeat adult and juvenile rat studies; however, there were no clinically relevant 
AEs/SAEs reported. 
To mitigate potential systemic risks, subjects will be monitored for AEs and any abnormal vital 
signs, physical examination, and laboratory test results. 
1.3.1.3. 
Reproductive and Developmental Toxicity 
Results of embryo-fetal development studies in rats and rabbits indicated an increased risk for 
embryo-fetal developmental effects, as evidenced by an increase in post-implantation loss and 
incidence of fetal skeletal variations. Results of a juvenile rat study indicated adverse 
microscopic changes in the form of renal pelvic dilatation in both sexes, along with reversible 
increases in total urinary glucose and protein excretion in males at ≥ 10/15 mg/kg/day tapinarof 
(administered subcutaneously). 
An investigative study in rats suggested an increased risk for hydronephrosis during a narrow 
window of postnatal sensitivity prior to postnatal day (PND) 32 (specifically PND 15 to 21). Rat 
renal tubule anatomic maturation and nephrogenesis occurs during this period [Cappon, 2010; 
Frazier, 2013; Zoetis, 2003], however tubule morphogenesis/nephrogenesis occurs entirely 
prenatally in humans [Cappon, 2010; Zoetis, 2003]. 
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To mitigate these potential risks, women of childbearing potential (CBP)must utilize abstinence 
or a highly effective method of contraception consistently and correctly during the study and for 
4 weeks after the end of treatment (Section 4.2). Monthly pregnancy testing will be conducted. 
Pregnant women and subjects under 18 years of age will be excluded from the study. If a woman 
becomes pregnant during the study, she will immediately discontinue study treatment. 
Additionally, AEs will be monitored and clinical laboratory testing will be performed. 
1.3.2. 
Benefit Assessment 
Subjects may experience improvements in their psoriasis during the course of the study and may 
benefit from the additional safety assessments conducted as part of the study 
(e.g., physical examination, laboratory tests). Subjects in the study will also contribute to the 
process of developing a novel anti-inflammatory agent for the topical treatment of psoriasis. 
1.3.3. 
Overall Benefit/Risk 
Taking into account the measures taken to minimize risk to subjects in this study, the potential 
risks identified in association with tapinarof are justified by the anticipated benefits that may be 
afforded to subjects with psoriasis. 
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3. 
STUDY DESIGN 
3.1. 
Overall Design 
This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical 
tapinarof cream, 1% in adults with plaque psoriasis. Subjects in this study completed treatment 
with tapinarof or vehicle in 1 of 2 pivotal Phase 3 pivotal efficacy and safety studies 
(Study DMVT-505-3001 or Study DMVT-505-3002). The study will consist of up to 40 weeks 
of treatment and a 4-week safety follow-up period. 
At the completion of the Week-12 Visit of the pivotal study (Baseline [Day 1] in this study), 
eligibility of the subjects opting to enroll in this extension study will be confirmed. Study visits 
during the treatment period for all subjects will occur every 4 weeks (±3 days). A Phone Call 
will be performed at Week 2 (Day 15).  Unscheduled visits may occur, as needed.  Subjects who 
withdraw from the study before Week 40 will return to the study center for an Early Termination 
Visit. The total duration of study participation will be approximately 44 weeks. 
Subjects in the study will be treated as follows based on their PGA score from the Week 12 visit 
in the pivotal study (DMVT-505-3001 or DMVT-505-3002). 
x Subjects entering with a PGA ≥ 1 will receive treatment with tapinarof cream, 1% 
until they achieve a PGA score of 0, at which time treatment will be discontinued and 
subjects monitored for durability of response. If/when disease worsening occurs, as 
evidenced by a PGA ≥ 2, treatment will then be re-initiated and continued until a 
PGA of 0 is observed. 
x Subjects entering with a PGA of 0 will have treatment discontinued and be monitored 
for durability of response. If/when disease worsening occurs, as evidenced by a PGA 
≥ 2, treatment will then be re-initiated and continued until a PGA of 0 is observed.    
x This treatment and re-treatment pattern of use will be continued until the end of the 
study (ie, subjects may receive study treatment up until the Week 40 visit) 
(see Section 5.1.5.2). 
Study drug will be dispensed, and subjects will be instructed on how to apply study drug. 
Subjects will apply the daily dose of study drug while at the site, under the supervision of site 
personnel, after efficacy and safety assessments have been completed. 
Study drug will be dispensed to subjects during the study visits and will be administered at home 
between study visits as instructed by site personnel. Subjects will be instructed to apply study 
drug once daily to all affected areas, including newly appearing lesions and lesions or affected 
areas that improve during the study. Subjects will apply sufficient study drug to cover 
completely each lesion with a thin layer of study drug and will record the time of study drug 
application in a daily diary provided by the study site. (Note that subjects are allowed, but not 
required, to treat fingernails, toenails, palms, soles, and scalp lesions with study drug; however, 
efficacy analyses will not include assessment of improvement of psoriasis in these areas.) 
Subjects will be instructed to maintain the approximate dosing time chosen at the beginning of 
the study for their full study participation. Study drug application instructions will be reviewed at 
subsequent study visits. During subsequent study visits, subjects will apply the daily dose of 
study drug while at the study under the supervision of site personnel, after efficacy and safety 
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assessments have been completed. The time of the dose application and assessments will depend 
on the time of the study visit (either morning or afternoon visit). Therefore, the timing of the 
study visit may lead to a change in the subject’s chosen dosing time; if this occurs, it will NOT 
be considered a protocol deviation; the subject should resume their chosen dosing time the day 
following any such clinic visit application. 
Rescue medications may be initiated with consultation of the medical monitor. 
Safety assessments will include AEs, local (application site) tolerability, clinical laboratory tests, 
vital signs, physical examinations, and investigator-assessed LTS. Efficacy assessments will 
include a 5-point static PGA (0-4 scale), %BSA affected, the PASI, and subject-reported DLQI. 
Refer to Section 6 for descriptions of study procedures and assessments and Section 7 and the 
Schedule of Assessments ( 
Table 1) for timing of procedures and assessments. 
3.2. 
Treatment Groups and Duration 
Subjects entering with a PGA ≥ 1 will receive treatment with tapinarof cream, 1% until they 
achieve a PGA score of 0, at which time treatment will be discontinued and subjects monitored 
for durability of response. If or when disease worsening occurs, as evidenced by a PGA ≥ 2, 
treatment will then be re-initiated and continued until a PGA of 0 is observed.  Subjects entering 
with a PGA of 0 will have treatment discontinued and be monitored for durability of response. 
If/when disease worsening occurs, as evidenced by a PGA ≥ 2, treatment will then be re-initiated 
and continued until a PGA of 0 is observed.  (Section 5.1.5.2). 
A subject will be considered to have completed the study when he/she completes all required 
procedures/visits for the 40-week (Visit 11) treatment period. The end of the study is defined as 
when the last active subject has completed the Follow-up Visit. 
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4. 
STUDY POPULATION 
4.1. 
Type and Number of Subjects 
Approximately 850 subjects who completed pivotal Study DMVT-505-3001 or pivotal 
Study DMVT-505-3002 will be enrolled in this study at approximately 100 to 120 study sites in 
the US and Canada. 
Protocol violations from inclusion and exclusion criteria are prohibited because ineligible study 
subjects can potentially jeopardize the scientific integrity of the study, regulatory acceptability, 
or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
4.2. 
Inclusion Criteria 
Each subject must meet all of the following criteria to be eligible to be enrolled in this study: 
1. Completed the 12-week treatment period in 1 of the 2 pivotal studies 
(Study DMVT-505-3001 or Study DMVT-505-3002)  
2. Male or female 
3. Female subjects of child-bearing potential and male subjects who are engaging in sexual 
activity that could lead to pregnancy should use one of the following acceptable birth 
control methods while on study and for 4 weeks after the last exposure to study drug.  
Acceptable contraception methods are: 
x Female subject or male subject’s female partner is surgically sterile (bilateral tubal 
ligation, hysterectomy, bilateral oophorectomy) for a minimum of 3 months prior to 
the first dose of study drug 
x Female subject or male subject’s female partner has had an intrauterine device in 
place for at least 3 months prior to the first dose of study drug 
x Double barrier methods (e.g., condom plus diaphragm, condom or diaphragm plus 
spermicide) starting at least 14 days prior to the first dose of study drug 
x Subjects who claim abstinence as their method of contraception are allowed provided 
they agree to use a double barrier method (e.g., condom plus diaphragm, condom or 
diaphragm plus spermicide) should they become sexually active from Screening to 1 
month after the last dose of study drug 
x Surgical sterilization of male subject or female subject’s partner (vasectomy) a 
minimum of 3 months prior to first dose of study drug 
x Female subject or male subject’s female partner is taking hormonal contraceptives 
starting at least 3 months prior to the first dose of study drug. If hormonal 
contraceptives were started less than 3 months prior to the first dose of study drug, 
subjects must agree to use a double barrier method (e.g., condom plus diaphragm, 
condom or diaphragm plus spermicide) from Screening through 3 months after the 
initiation of hormonal contraceptives 
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The Investigator is responsible for 
ensuring that subjects understand how to properly use these methods of contraception. 
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Non-CBP is defined as premenarchal or premenopausal females with a documented 
bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy, 
or hysteroscopic sterilization; or postmenopausal females defined as a cessation of 
menses for at least 12 months without an alternative medical cause. In questionable cases 
a blood sample with simultaneous follicle stimulating hormone (FSH) >40 ml/U is 
confirmatory. Documented verbal history from the subject is acceptable. 
Female subjects of CBP must have a negative urine pregnancy test at Baseline (Day 1), as 
collected from Week 12 of 1 of the 2 pivotal studies (Study DMVT-505-3001 or 
Study DMVT-505-3002). 
4. Capable of giving signed informed consent, as applicable, which includes compliance 
with the requirements and restrictions listed in the informed consent form (ICF); written 
informed consent must be obtained prior to any study related procedures. 
4.3. 
Exclusion Criteria 
Any subject who meets any of the following criteria will be ineligible to be enrolled in this 
study: 
1. Used a prohibited concomitant product or procedure to treat psoriasis during pivotal 
study 
2. Had an SAE that was potentially related to treatment or experienced an AE that led to 
permanent discontinuation of treatment in the pivotal study 
3. History of or ongoing serious illness or medical, physical, or psychiatric condition(s) that, 
in the Investigator’s opinion, may interfere with the subject’s completion of the study 
4. Known hypersensitivity to tapinarof or excipients 
4.4. 
Lifestyle Restrictions 
Subjects should avoid prolonged exposure to natural or artificial sources of ultraviolet (UV) 
radiation (e.g., sunlight or tanning booth) and UV light therapy during this study, because UV 
light may affect the subject’s psoriasis. The use of sunscreen on nonlesional areas is allowed. 
4.5. 
Screening Failure 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently enrolled. A minimal set of screen failure information is required to ensure 
transpivotal reporting of screen failure subjects to meet the Consolidated Standards of Reporting 
Trials publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAEs. These 
data will also be linked to subject data from the initial study. 
4.6. 
Withdrawal Criteria 
A subject may voluntarily discontinue treatment and/or withdraw from participation in this study 
at any time at his/her own request, or may be discontinued from study treatment at any time at 
the discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. 
Subjects withdrawn from the study will not be replaced. 
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4.6.1. 
Reasons for Withdrawal from Study 
Study drug will be discontinued for any of the following reasons: 
x Subject has an AE that is considered to be related to study drug or procedures AND is 
severe enough to warrant treatment discontinuation, as determined by the Investigator 
(Section 8.1) 
x Subject requires concurrent prohibited concomitant medication during the study. If, in 
the opinion of the Investigator and the study Medical Monitor, such medication will 
not interfere with the conduct or interpretation of the study or compromise the safety 
of the subject, then the subject may continue to receive study drug. If the subject is 
discontinued from study drug, they may remain in the study for safety assessments as 
needed, at the discretion of the Investigator and Medical Monitor. 
x Pregnancy 
x Any Grade 3 or 4 AE considered causally related to study drug (Section 8.2.2) 
Study drug may be discontinued for any of the following reasons: 
x Subject noncompliance 
x Investigator noncompliance 
x Discontinuation of the study at the request of the Sponsor, regulatory agency, or an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
If a subject meets a withdrawal criterion during treatment, an Early Termination Visit will be 
required (Section 7.7). 
4.6.2. 
Temporary Discontinuation 
A subject will discontinue study drug when the Investigator determines a PGA of 0 has been 
achieved as described in Section 5.1.5.1. While actively treating an episode of disease worsening 
or during the treatment course for a PGA ≥ 2, there are no specific provisions for temporary 
discontinuation of treatment during this study, with the exception of the interruption of study 
treatment for skin irritation (see Section 1.3). If study treatment is interrupted due to a safety 
issue, the Medical Monitor will be contacted and the event documented in the electronic case 
report form (eCRF). 
4.6.3. 
Withdrawal Procedures 
The primary reason for the discontinuation of study drug and/or withdrawal from study must be 
recorded in the source document and on the eCRF. If a subject is prematurely discontinued from 
study drug(s), the Investigator must make every effort to perform an Early Termination Visit 
(Section 7.7) and document the primary reason for withdrawal. 
Should a subject fail to attend a required study visit, the site should attempt to contact the subject 
and re-schedule the missed visit as soon as possible. The site should also counsel the subject on 
the importance of maintaining the assigned visit schedule and ascertain whether the subject 
wishes to and/or should continue in the study based on previous non-compliance. In cases where 
the subject does not return for the rescheduled visit or cannot be reached to reschedule the 
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missed visit, the site should make every effort to regain contact with the subject so that they can 
appropriately be withdrawn from the study with a primary reason of “Lost to Follow-up.” 
4.7. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he/she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. The following actions must be taken if a 
subject fails to return to the clinic for a required study visit: 
x The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 
x Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
x Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
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5. 
STUDY TREATMENT 
5.1. 
Study Drug 
5.1.1. 
Description, Packaging, and Labeling 
The description of the study drug is presented in Table 2. 
Table 2 
Tapinarof Cream 
Drug name: 
DMVT-505 (tapinarof) 
Physical description 
White to off-white cream 
Unit dose strength/how supplied 
1% (10 mg/g)/30 gram, tube 
Route of administration/duration 
Topical/up to 40 weeks 
Dosing instructions: 
Once daily topical application of thin layer to all affected 
areas (see Section 5.1.5) 
Manufacturer 
GlaxoSmithKline 
 
Study drug will be dispensed to subjects at the clinical site in appropriately labeled tubes. All 
labels for tapinarof cream, 1% to be distributed in the participating countries will meet all 
applicable requirements of those countries. 
5.1.2. 
Storage 
All study drug must be stored in a secure environmentally-controlled and monitored (manual or 
automated) area in accordance with the labelled storage conditions, with access limited to the 
Investigator and authorized site staff. 
5.1.3. 
Handling and Disposal 
Under normal conditions of handling and administration, study drug is not expected to pose 
significant safety risks to site staff. In the case of unintentional occupational exposure notify the 
monitor, Medical Monitor and/or the Sponsor study contact. 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational hazards and 
recommended handling precautions either will be provided to the Investigator, where this is 
required by local laws, or is available upon request from the Sponsor. 
Arrangements will be made for used and unused drug supplies to be returned to the Sponsor or 
Sponsor designee, or for destruction on site following acceptable, documented procedures. 
Further guidance and information for final disposition of unused study drug will be provided. 
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5.1.4. 
Preparation 
No special preparation of study drug is required. 
5.1.5. 
Administration of Study Drug 
5.1.5.1. 
Treatment by Physician Global Assessment Score 
Subjects entering with a PGA ≥ 1 will receive treatment with tapinarof cream, 1% until they 
achieve a PGA score of 0.  If/when disease worsening occurs, as evidenced by a PGA ≥ 2, 
treatment will then be re-initiated and continued until a PGA of 0 is observed.  Subjects entering 
with a PGA of 0 will have treatment discontinued and be monitored for durability of response. 
If/when disease worsening occurs, as evidenced by a PGA ≥ 2, treatment will then be re-initiated 
and continued until a PGA of 0 is observed. This treatment and re-treatment pattern of use will 
be continued until the end of the study (i.e., subjects may receive study treatment up until the 
Week 40 visit). 
 
 Subjects who experience suspected disease worsening between scheduled study visits may 
contact the study site to arrange an unscheduled visit (Section 7.5). See Disease Worsening 
(PGAt2) During the Study (Section 5.1.5.2) for further instructions. Upon confirmation of 
disease worsening, subjects will restart treatment with study drug. 
5.1.5.2. 
Disease Worsening (Physician Global Assessment Score ≥ 2) During the Study 
If disease worsening is suspected between scheduled study visits, an unscheduled visit may 
be performed. 
x If disease worsening (ie, PGA ≥ 2) is not confirmed, the subject will continue to be 
assessed at routine, scheduled visits (see Table 1). 
x For each confirmed episode of disease worsening (ie, PGA ≥ 2) during the study (at 
either a scheduled or unscheduled visit), a treatment course of tapinarof cream (once 
daily) will be initiated and will continue until the subject achieves a PGA 0, as 
assessed at scheduled visits, approximately every 4 weeks (see Table 1). 
x Subjects subsequently achieving a PGA of 0 will stop study drug and will then be 
assessed at routine, scheduled visits (see  
x Table 1). Subjects who then experience suspected disease worsening between 
scheduled study visits may contact the study site to arrange an unscheduled visit (see  
x Table 1). 
 If disease worsening is not confirmed, the subject will continue to be assessed at 
routine, scheduled visits. 
 If disease worsening is confirmed (ie, PGA ≥ 2) at either an unscheduled or a 
scheduled visit, subjects will initiate another treatment course of tapinarof cream 
(once daily) until a PGA 0 is achieved as described above. 
x This treatment and re-treatment pattern of use will be continued until the end of the 
study (ie, subjects may receive study treatment up until the Week 40 visit). 
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5.1.5.3. 
Application of Study Drug 
Study drug will be dispensed to subjects requiring treatment at the study visits specified in the 
Schedule of Assessments ( 
Table 1). 
Subjects will take the tubes home and self-administer (or have a caregiver apply if necessary), 
except on study visit days (when study drug is applied under supervision at the site), to affected 
areas once daily. 
Subjects will be instructed to apply study drug as follows: 
x For subjects with a PGA > 0, once daily application to affected areas including those 
areas treated in the pivotal study; subjects are to choose the application time they 
prefer and to apply the study drug at that time each day of study participation. 
x Subjects with a PGA of 0 will not receive treatment but if they worsen and experience 
a PGA of ≥ 2, apply once daily to newly affected areas only. 
x If a subject misses a daily dose, it will be recorded as a protocol deviation. The 
subject should continue dosing the next day and should not apply more than once 
daily to make up for the missed dose on the previous day. 
x If chosen application time is in the evening, the dose should be applied at least 
30 minutes prior to bedtime. 
x Study drug should be applied to dry, clean skin 
x Wash hands after application, unless treating lesions on the hands or fingernails. 
x Study drug should be applied to all lesions, including newly appearing lesions and 
lesions that have improved during the study. 
x Subjects are allowed, but not required, to treat fingernails, toenails, palms, soles, and 
scalp lesions with study drug; however, efficacy analyses will not include assessment 
of improvement of psoriasis in these areas). If using study drug on the scalp, no other 
treatment for scalp psoriasis is permitted during the study. 
x If there is residual cream visible on the disease-affected lesional skin, then the subject 
should be instructed to continue to lightly rub the cream into the skin until it is no 
longer visible 
x If study drug is applied to the subject by another person, that person should 
thoroughly wash his/her hands after application. When possible, use of disposable 
gloves is recommended. 
x Subjects should record the time of study drug application in the daily diary. 
x Subjects should avoid swimming, bathing, showering, or strenuous activities for at 
least 2 hours after application of study drug. 
x On study visit days, study drug should be applied in the clinic under the supervision 
of site personnel and after safety assessments have been completed 
NOTE: The time of the dose and assessments on study visit days will depend on the 
time of the study visit (either morning or afternoon visit). Therefore, the timing of the 
study visit may differ from the subject’s chosen dosing time (morning or evening); if 
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this occurs, it should not be recorded as a protocol deviation and the subject should 
resume their chosen dosing time following any such study visit. The intention is to 
allow flexibility to accommodate subjects’ schedules. 
5.2. 
Randomization/Treatment Assignment 
All subjects will receive treatment with tapinarof cream, 1% as needed per protocol. 
5.3. 
Blinding 
This study is an open-label study; blinding is not applicable. 
5.4. 
Compliance with Study Drug Administration 
At baseline, study staff will provide the subject with detailed instructions concerning protocol 
requirements and use of study drug in this extension study. Additionally, subjects will be asked 
to complete a daily diary with the time of each application of study drug. At each postbaseline 
study visit, study staff will review use of study drug, as applicable, with the subject. 
When subjects are dosed at the site, they will apply the study drug under supervision of the study 
staff. The date and time of each dose administered in the clinic will be recorded in the source 
documents. The study drug and study subject identification will be confirmed at the time of 
dosing by a member of the study site staff. 
At the time of dispensing study drug to each subject, site personnel will weigh the tubes to be 
dispensed and will record the weight of all tubes dispensed at each visit in the drug 
accountability logs. Subjects will be instructed to bring all used and unused tubes with them to 
each study visit. Site personnel will weigh the returned tubes (used and unused) and record the 
weight in the drug accountability logs. If a tube has been lost, discarded, or forgotten by the 
subject, the site personnel will make a notation of this on the drug accountability logs. The site 
personnel will remind the subject to keep all tubes of study drug dispensed and to bring all used 
and unused tubes to each study visit. These data will be used to estimate subject compliance with 
use of study drug. Tubes of study medication dispensed at the most recent prior visit, which 
remain unopened (the foil cap on the tube remains fully intact/undisturbed) may be redispensed 
to study subjects at the current visit. Unopened tubes may only be dispensed one time. Opened, 
partially used tubes, or tubes with foil overlay removed are not to be redispensed to study 
subjects. If there is any question as to redispensation, sites should issue new tubes of study 
medication to the subject(s). 
5.5. 
Treatment after the End of the Study 
Subjects will not receive any additional treatment with the study drug from the Sponsor after 
completion of the study. The indication being studied is not life threatening or seriously 
debilitating, and other treatment options are available. 
The Investigator is responsible for ensuring that consideration has been given to the poststudy 
care of the subject’s medical condition, whether or not the Sponsor is providing specific 
poststudy drug. 
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5.6. 
Prior and Concomitant Therapy 
 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
5.6.1. 
Permitted Medications and Nondrug Therapies 
Concomitant medications for medical treatment of other conditions are allowed, under the 
condition that the dosage and administration of these treatments is not planned to change from 
the Baseline visit to the completion of the study or discontinuation, and that the medication is not 
a prohibited medication as described in Section 5.6.2. In the event of skin infection, topical 
antibacterial agents can be applied to the infected area; however, study drug must not be applied 
to the area until the skin infection is healed. 
Subjects may use nonmedicated shampoos (must not contain corticosteroids, vitamin D analogs, 
salicylic acid, or coal tar). Nonmedicated emollients may be used on nonlesional skin; emollients 
should not be applied to lesional skin during active treatment courses and should not be applied 
on the morning of study visits. The same emollient should be used throughout the subject’s 
participation in the study. 
Note: Any emollient used during the study must be recorded as a concomitant medication. 
5.6.2. 
Prohibited Medications and Nondrug Therapies 
Medications and nondrug therapies that are prohibited throughout the study duration are as 
follows: 
x Biologic agents: rituximab, ustekinumab, secukinumab, golimumab, ixekizumab, 
infliximab, adalimumab, alefacept, etanercept (list is not exclusive, contact Medical 
Monitor for questions) 
x Systemic treatments: cyclosporin, interferon, methotrexate, apremilast, tofacitinib, 
mycophenolate, thioguanine, hydroxyurea, sirolimus, azathioprine, other systemic 
immunosuppressive or immunomodulating agents, fumaric acid derivatives, vitamin 
D3 and analogs (>5000 IU / day), retinoids (e.g., acitretin, isotretinoin), psoralens, 
corticosteroids, or adrenocorticotropic hormone analogs 
x Ultraviolet light: therapy or prolonged exposure to natural or artificial sources of UV 
radiation (e.g., phototherapy, tanning beds/booths, or therapeutic sunbathing) 
x Topical treatments: corticosteroids, antihistamines, immunomodulators, anthralin 
(dithranol), Vitamin D derivatives (e.g., calcipotriene, calcipotriol), retinoids 
(e.g., tazarotene), or coal tar 
x Drugs known to possibly worsen psoriasis (unless on a stable dose for 
>12 weeks): beta blockers (e.g., propranolol), lithium, iodides, angiotensin-
converting enzyme inhibitors, and indomethacin 
x Immunizations: live, attenuated vaccines (inactivated or subunit vaccines are 
acceptable when required) 
x Other: any Investigational products or procedures 
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6. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and assessments are summarized in the Schedule of Assessments (Table 1) and 
in Section 7. Adherence to the study design requirements, including those specified in the 
schedule of activities, is essential and required for study conduct. Protocol waivers or 
exemptions are not allowed. 
6.1. 
Medical History and Demography 
6.1.1. 
Medical History 
Medical, medication, and family history collected during the pivotal study will be used for 
this study. 
6.1.2. 
Demographics 
The demographic information collected during the pivotal study will be used for this study, 
including: age, sex, race, and ethnicity. 
6.2. 
Efficacy Assessments 
To minimize interobserver variability, investigators and evaluators/raters will be trained on each 
of the required assessments during an investigator meeting, site initiation visit, and/or utilizing 
online assessments before enrolling subjects at their study center. Only trained evaluators/raters 
are permitted to perform the efficacy assessments. To the fullest extent possible, the same 
investigator (or designated evaluator/rater) will perform all efficacy assessments for an 
individual subject throughout the study. If it is not possible for the same evaluator/rater to 
continue performing assessments, it is recommended that the primary and subsequent 
evaluator/rater both examine and discuss their respective scoring during at least 1 visit. 
6.2.1. 
Assessments by Investigator 
6.2.1.1. 
Physician Global Assessment 
The PGA is a clinical tool for assessing the current state/severity of a subject’s psoriasis at a 
given timepoint. It is a static 5-point morphological assessment of overall disease severity, as 
determined by the Investigator, using the clinical characteristics of erythema, scaling, and plaque 
thickness/elevation as guidelines; higher PGA scores represent more severe disease. The BSA 
affected is not considered in scoring of the PGA (see Section 6.2.1.2). Variations of the PGA are 
frequently used in clinical studies because it is a simple assessment that is more similar to the 
assessments actually used in clinical practice (see Appendix 1 for details). The PGA should be 
performed first, prior to %BSA, PASI, and LTS assessments. 
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6.2.1.2. 
Body Surface Area 
The assessment of the %BSA is an estimate of the percentage of total involved skin with 
psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject’s palm 
and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by 
psoriasis will be evaluated (from 0 to 100%). Details on calculation of approximate %BSA 
involvement in each subject (total and individual are provided in Appendix 2). Percentage BSA 
is a static assessment made without reference to previous scores. 
Note: for all efficacy assessments, lesions on the subject’s scalp, palms, fingernails, toenails, and 
soles will not be included in the calculation of %BSA affected as these areas will not be included 
in the efficacy analyses. 
6.2.1.3. 
Psoriasis Area and Severity Index 
The PASI scoring system is a widely-used standard clinical tool for assessing the severity of 
psoriasis that takes into account the overall severity of erythema (redness), induration (plaque 
thickness), and scale, and the extent of %BSA affected with psoriasis. The 3 clinical signs are 
each graded on a 5-point scale (0 to 4) and the %BSA affected is scored on a 7-point scale 
(0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk, and lower 
extremities). The individual scores are multiplied by a weighted factor for each body region; the 
sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. 
PASI is a static assessment made without reference to previous scores. See Appendix 2. 
6.2.2. 
Assessments Completed by Subject  
6.2.2.1. 
Dermatology Life-Quality Index 
Subjects will complete the DLQI questionnaire. The DLQI is simple dermatology-specific 
10-question validated questionnaire to assess the impact of the disease on a subject’s quality 
of life (Cardiff University, Department of Dermatology, Quality of Life Questionnaires). 
The DLQI has become an important outcome measure in dermatology clinical trials and is 
the most frequently used instrument in studies of randomized controlled trials in dermatology 
[Basra, 2015]. The DLQI can be analyzed as a total score (where a higher score indicates greater 
impairment in quality of life) and can also be scored for the following dimensions: Symptoms 
and Feelings (items 1 and 2), Daily Activities (items 3 and 4), Leisure (items 5 and 6), Work and 
School (item 7), Personal Relationships (items 8 and 9), and Treatment (item 10). An example of 
this assessment is provided Appendix 3. For additional information, refer to the Study Reference 
Manual. 
6.2.2.2. 
Patient Satisfaction Questionnaire 
Subjects will complete the Patient Satisfaction Questionnaire. The Patient Satisfaction 
Questionnaire is provided in Appendix 5. 
6.2.3. 
Optional Clinical Photography 
Clinical photography may be performed in a subgroup of subjects at selected study centers that 
participated in photography in the pivotal study. This is not required of subjects for participation 
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in the study. Informed consent and photographic release will be required. The photographs may 
not be referred to by the Investigator at any subsequent study visit for the purposes of grading. 
Photographs will be taken of a representative area of the subject’s disease area at the time points 
specified in the Schedule of Assessments (Table 1; see also section 7). Three photographs of the 
selected skin area will be taken in a standardized fashion (ie, same camera, angle, background, 
distance). Procedures for the clinical photography will be contained in the Photography Manual. 
6.3. 
Safety Assessments 
6.3.1. 
Adverse Events 
All AEs will be collected from the time the subject signs the ICF until the final visit/contact with 
the subject. Adverse events that began during the pivotal study and were ongoing at the end of 
that study will be reported as ongoing AEs. Additional safety information, including the 
definition of an AE and the methods for recording, evaluating, and assessing causality of AEs 
and the procedures for completing and transmitting SAE reports are provided in Section 8. 
6.3.2. 
Brief Physical Examination 
A brief physical examination will include, at a minimum, assessments of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen). Investigators should pay special 
attention to clinical signs related to previous serious illness. 
6.3.3. 
Vital Signs 
Vital signs will be measured before blood collection for clinical laboratory assessments and will 
include measurements of systolic and diastolic blood pressure, pulse rate, and body temperature. 
Subjects should be in a seated position for at least 5 minutes. 
6.3.4. 
Clinical Safety Laboratory Assessments 
All protocol-required laboratory assessments must be conducted in accordance with the Study 
Reference Manual or Laboratory Manual, and Protocol Schedule of Assessments. Laboratory 
requisition forms must be completed, and samples must be clearly labeled with the Subject 
number, protocol number, site/center number, and visit date. Details for the preparation and 
shipment of samples will be provided by the laboratory and are detailed in the Study Reference 
Manual or the Laboratory Manual. Reference ranges for all safety parameters will be provided to 
the site by the laboratory responsible for the assessments. 
A list of clinical laboratory tests and parameters is provided in Table 3. 
All laboratory tests with values that are considered clinically significantly abnormal during 
participation in the study should be repeated until the values return to normal or baseline. If such 
values do not return to normal within a period judged reasonable by the Investigator, the etiology 
should be identified, if possible, and the Sponsor notified. 
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6.3.5. 
Local Tolerability Scale 
At each specified study visit and if the subject is receiving study drug, the Investigator (or 
qualified evaluator) will assess the presence and overall degree of irritation at the application 
sites, according to the LTS (an example of the LTS is provided in Appendix 4). The score will 
ideally represent an ‘average’ across all application sites. To the fullest extent possible, the same 
Investigator (or designated evaluator) will perform all tolerability assessments for an individual 
subject throughout the study. If the subject is applying study treatment to “sensitive areas” 
(e.g., genitals, face, neck, and skin folds), then the degree of irritation for these areas should also 
be assessed by the investigator. 
Additionally, at each specified study visit if receiving study drug, the subject will use a 5-point 
LTS to assess the presence and degree of burning/stinging and itching at the treatment areas. The 
score will ideally represent an ‘average’ across all application sites. 
6.4. 
Treatment of Study Drug Overdose 
For this study, accidental or intentional ingestion of the study drug is considered an overdose. 
Ingestion of a 30-gram tube of 1% cream would result in an oral dose of 300 mg. 
The Sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator (or treating physician) should: 
x Contact Medical Monitor to discuss the event 
x In the event of excessive topical application, instruct the subject to wash study drug 
off of the skin and monitor for application-site AEs. 
x Monitor subject for systemic AEs/SAEs and clinically significant laboratory 
abnormalities. 
x Obtain blood sample within 2 days from the date of last application of study drug or 
date of ingestion to determine possible systemic exposure to study drug (if requested 
by the Medical Monitor; determined on a case-by-case basis) 
x Provide general symptomatic treatment as necessary 
x Document quantity of excess dose (e.g., by weighing the tube of cream) and duration 
of exposure, in the eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the subject. 
6.5. 
Pharmacokinetics/Pharmacodynamics 
Pharmacokinetics/pharmacodynamics will not be performed in this study. 
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7. 
TIMING OF PROCEDURES AND ASSESSMENTS 
This section lists the procedures and assessment to be performed at scheduled timepoints during 
the study as outlined in the Schedule of Assessments ( 
Table 1). Information on study procedures and assessments is provided in Section 6. 
x Any change in timing or any addition of a time point(s) for any planned study 
assessment must be documented in a “Note to File,” which is approved by the 
relevant Sponsor study team member and then archived in the study Sponsor and site 
study files; this will NOT constitute a protocol amendment. 
x The IRB/IEC will be informed of any safety issues that require alteration of the safety 
monitoring scheme or amendment of the ICF. 
NOTE: Assessments and procedures should be performed predose on study visit days. 
7.1. 
Visit 1; Baseline 
On Day 1, subjects from the pivotal studies who were considered eligible for this study will sign 
the ICF and be reassessed to confirm eligibility to participate in this study. All subjects who 
continue to meet study eligibility criteria will be enrolled. Subjects entering with a PGA ≥ 1 will 
receive treatment with tapinarof cream, 1% until they achieve a PGA score of 0, at which time 
treatment will be discontinued and subjects monitored for durability of response.  If/when 
disease worsening occurs, as evidenced by a PGA ≥ 2, treatment will then be re-initiated and 
continued until a PGA of 0 is observed.  Subjects entering with a PGA of 0 will have treatment 
discontinued and be monitored for durability of response  
The following procedures and assessments will be performed at the Baseline Visit: 
x Brief physical exam (last assessment from pivotal study) 
x Vital signs measurements (last assessment from pivotal study) 
x Urine pregnancy test (females of CBP; last assessment from pivotal study) 
x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests; last assessment from pivotal study) 
x Urinalysis  
x Photography of a representative area of the subject’s disease area (optional for 
subjects; at a subset of study centers) (last assessment from pivotal study) 
x PGA score (last assessment from pivotal study) 
x BSA affected calculation (last assessment from pivotal study) 
x PASI (last assessment from pivotal study) 
x DLQI (last assessment from pivotal study) 
x AE recording (Including any ongoing AEs from the pivotal study and from the time 
the ICF is signed) 
x Concomitant medication recording (from the time ICF is signed) 
x Diary dispensed (subjects will be instructed in how and when to complete diary), if 
applicable 
x Dispense study drug, if applicable 
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x Instruction on how to apply study drug, if applicable 
x Study drug application under supervision, if applicable 
7.2. 
Visits 2 to 10; Treatment Period 
Subjects entering with a PGA ≥ 1 will receive treatment with tapinarof cream, 1% until they 
achieve a PGA score of 0, at which time treatment will be discontinued and subjects 
monitored for durability of response.  If/when disease worsening occurs, as evidenced by a 
PGA ≥ 2, treatment will then be re-initiated and continued until a PGA of 0 is observed.  
Subjects entering with a PGA of 0 will have treatment discontinued and be monitored for 
durability of response. If/when disease worsening occurs, as evidenced by a PGA ≥ 2, 
treatment will then be re-initiated and continued until a PGA of 0 is observed.  Subjects will 
return to the study site at least every 4 weeks (±3 Days) during the 40-week monitoring 
period. The following assessments will be performed: 
x Brief physical exam 
x Vital signs measurements 
x Urine pregnancy test (females of CBP) 
x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests); Weeks 4, 12 only 
x Photography of a representative area of the subject’s disease area (optional for 
subjects; at a subset of study centers)  
x PGA score 
x BSA affected calculation 
x PASI 
x LTS (if patient has been applying study drug for the treatment period prior to the 
scheduled visit) 
x DLQI 
x AE recording 
x Concomitant medication recording 
x Collect and dispense diary, if applicable (subjects will be instructed in how and when 
to complete diary) 
x Review diary for treatment compliance, if applicable 
x Dispense and collect study drug, if applicable 
x Instruction on how to apply study drug, if applicable 
x Study drug application under supervision, if applicable 
7.3. 
Visit 11;  
The following procedures and assessments will be performed at the Week 40 Visit: 
 
x Brief physical exam 
x Vital signs measurements 
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x Urine pregnancy test (females of CBP) 
x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests) 
x Urinalysis 
x Photography of a representative area of the subject’s disease area (optional for 
subjects; at a subset of study centers)  
x PGA score 
x BSA affected calculation 
x PASI 
x LTS (if patient has been applying study drug for the treatment period prior to the 
scheduled visit) 
x DLQI 
x Patient Satisfaction Questionnaire 
x AE recording 
x Concomitant medication recording 
x Collect diary, if applicable  
x Review diary for treatment compliance, if applicable 
x Collect study drug, if applicable 
7.4. 
Follow-up Visit 
Subjects will return to the study site 4 weeks (±3 days) after last treatment to complete follow-up 
assessments as follows: 
x Brief physical exam 
x Vital signs measurements 
x Urine pregnancy test (females of CBP) 
x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests) 
x Urinalysis 
x Photography of a representative area of the subject’s disease area (optional for 
subjects; at a subset of study centers) 
x PGA score 
x BSA affected calculation 
x PASI 
x DLQI 
x AE recording 
x Concomitant medication recording 
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7.5. 
Phone Contact at Week 2 (Day 15 ±3 Days) 
Subjects will be contacted by Phone at Week 2 to review study drug application instructions and 
to record AEs and concomitant medication use.  Subjects should be reminded to complete their 
daily diary and bring it with them to the next study visit. 
7.6. 
Unscheduled Visits 
Unscheduled visits may occur, as needed. For subjects who experience suspected disease 
worsening (PGA ≥ 2) between scheduled study visits may contact the study site to arrange an 
unscheduled visit (see Section 5.1.5.2). The following assessments will be performed: 
x Brief physical exam 
x Vital signs measurements 
x Urine pregnancy test (females of CBP), as needed 
x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests), as needed 
x Urinalysis, as needed 
x Photography of a representative area of the subject’s disease area (optional for 
subjects; at a subset of study centers)  
x PGA score 
x BSA affected calculation 
x PASI 
x LTS (if patient has been applying study drug for the treatment period prior to the 
scheduled visit) 
x AE recording 
x Concomitant medication recording 
x Collect and dispense diary, if applicable (subjects will be instructed in how and when 
to complete diary) 
x Review subject diaries for treatment compliance, if applicable 
x Collect and dispense study drug (if applicable) 
x Instruction on how to administer study drug (if applicable) 
x Study drug administration under supervision (if applicable) 
If disease worsening is confirmed, a new treatment course will be initiated. 
7.7. 
Early Termination 
Subjects who withdraw early from the study will be asked to return to the study site to complete 
Early Termination assessments as follows: 
x Brief physical exam 
x Vital signs measurements 
x Urine pregnancy test (females of CBP) 
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x Blood sample collection for clinical laboratory tests (serum chemistry, hematology, 
diagnostic tests) 
x Urinalysis 
x Photography of a representative area of the subject’s disease area area (optional for 
subjects; at a subset of study centers) 
x PGA score 
x BSA affected calculation 
x PASI 
x LTS (if patient has been applying study drug for the treatment period prior to the 
scheduled visit) 
x DLQI 
x Patient Satisfaction Questionnaire  
x AE recording 
x Concomitant medication recording 
x Collect and review subject diaries for treatment compliance 
x Collect study drug 
7.8. 
End of Study 
The end of the study is defined as when the last active subject has completed the Follow-up Visit 
(Week 44). 
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8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events, Serious Adverse Events, and Adverse events of 
Special Interest 
The Investigator or site staff is responsible for detecting, documenting and reporting events that 
meet the definition of an AE, SAE, or adverse event of special interest (AESI). At each 
visit/contact, subjects should be questioned in a general way so as not to introduce bias in 
detecting AEs and/or SAE. Open-ended and non-leading verbal questioning of the subject is the 
preferred method to inquire about AE occurrence. 
Investigators are not obligated to actively seek AEs or SAEs in former study subjects. However, 
if the Investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event reasonably related to the study drug or 
study participation, the Investigator would promptly notify the Sponsor. 
8.1.1. 
Definition of Adverse Events 
An AE is any untoward medical occurrence in a subject temporally associated with the use of a 
medicinal product, whether considered causally related or not related to the medicinal product. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal product. 
Events that meet the definition of an AE include: 
x Any abnormal laboratory test results (hematology, clinical chemistry) or other safety 
assessments (e.g., vital signs measurements), including those that worsen from 
baseline, and felt to be clinically significant in the medical and scientific judgment of 
the Investigator 
x Exacerbation of a chronic or intermittent pre-existing condition (e.g., atopic 
dermatitis) including either an increase in frequency and/or intensity of the condition 
 For skin-related AEs, it should be noted whether or not the event is in the area of 
active application of study medication, and/or if spreading beyond the application 
site. 
x New conditions detected or diagnosed after study drug administration even though it 
may have been present prior to the start of the study 
x Signs, symptoms, or the clinical sequelae of a suspected interaction 
x Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug 
or a concomitant medication (overdose per se will not be reported as an AE/SAE) 
x "Lack of efficacy" or "failure of expected pharmacological action" per se will 
not be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition of an 
AE or SAE. 
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x Symptomatic complaints at the site of local application (e.g., burning/stinging, 
pruritus, erythema) 
Events that do not meet the definition of an AE include: 
x Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the Investigator 
to be more severe than expected for the subject’s condition 
x The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition 
x Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE 
x Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital) 
x Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen 
8.1.2. 
Definition of Serious Adverse Event 
If an event is not an AE per Section 8.1.1, then it cannot be an SAE even if serious conditions are 
met (e.g., hospitalization for signs/symptoms of the disease under study, death due to progression 
of disease, etc.). 
An SAE is any untoward medical occurrence that, at any dose: 
x Results in death 
x Is life-threatening 
 The term “life-threatening” refers to an event in which the subject was at risk of 
death at the time of the event; does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
x Requires hospitalization or prolongation of existing hospitalization 
 In general, this signifies that the subject has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or 
treatment that would not have been appropriate in the physician’s office or 
out-patient setting. Complications that occur during hospitalization are AEs. 
If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
x Results in disability/incapacity: a substantial disruption of a person’s ability 
to conduct normal life functions 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
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influenza, and accidental trauma (e.g., sprained ankle), which may interfere or 
prevent everyday life functions but do not constitute a substantial disruption. 
x Results in a congenital anomaly/birth defect 
x Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
8.1.3. 
Adverse Events of Special Interest 
In prior clinical studies, the following AEs have been identified as AEs of particular clinical 
importance and will be reported as AESIs in this study; in each case, study drug may be 
discontinued, and study drug may be restarted when event resolves: 
x Contact dermatitis: the study site should collect location, duration, size, associated 
symptoms (itching, burning, pain), severity (mild, moderate, severe), and photograph 
the affected site (if possible). If the subject contacts the study site to report significant 
skin irritation at or near the site of study drug application between study visits, the 
subject should be brought for an unscheduled visit, if possible. 
x Folliculitis: the study site should collect the location, duration, size, associated 
symptoms (itching, burning, pain), severity (mild, moderate, severe), indicate whether 
pustular, and photograph the affected site (if possible) 
x Headache: the study site should collect duration, severity (mild, moderate, severe), 
onset, and location  
Additional AESIs may be identified by the Drug Safety Physician and if applicable by the 
Clinical Study Team Physician during the evaluation of safety data for the Clinical Study Report. 
For each AESI, a narrative may be written and included in the Clinical Study Report. 
8.2. 
Classification of Adverse Events 
8.2.1. 
Assigning Severity Rating for Adverse Events 
8.2.1.1. 
Criteria for Determining Adverse Event Severity 
The Investigator will make an assessment of the severity of each AE and SAE according to the 
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), v. 5.0, 
2017. For terms not specified with the CTCAE, the criteria in Table 4 should be used to 
determine the grade severity. 
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Table 4: 
Criteria for Determining the Grade/Severity of Adverse Event Terms Not 
Specified by the National Cancer Institute CTCAE 
Grade 
Criteria 
1 
Mild; asymptomatic or mild symptoms, clinical or diagnostic observations only; intervention not 
indicated 
2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental 
activities of daily livinga 
3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care activities of daily livingb 
4 
Life threatening consequences; urgent intervention indicated 
5 
Death related to adverse event 
CTCAE = Common Terminology Criteria for Adverse Events. 
a  Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
b  Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
 
Adverse event severity should be recorded in the appropriate section of the adverse event case 
report form and in the subject’s source documents. 
8.2.1.2. 
Toxicity Management Criteria 
8.2.1.2.1. Grade 1 or Grade 2 Adverse Event 
Subjects who develop a Grade 1 or Grade 2 AE may continue study drug at the discretion of the 
Investigator. Subjects who choose to withdraw from study due to a Grade 1 or 2 AE should have 
study withdrawal / follow-up evaluations completed. 
8.2.1.2.2. Grade 3 Adverse Event 
Subjects who develop a Grade 3 AE should be managed as follows: 
x If the Investigator has compelling evidence that the Grade 3 AE has not been caused 
by study drug, then dosing may continue after discussion with the Medical Monitor. 
x Subjects who develop a Grade 3 AE that the Investigator considers related or possibly 
related to study drug should have the study drug discontinued. Subjects experiencing 
Grade 3 AEs requiring permanent discontinuation of study drug should be followed 
weekly until resolution or stability of the AE and encouraged to have withdrawal 
study evaluations completed. 
8.2.1.2.3. Grade 4 Adverse Event 
Subjects who develop a Grade 4 AE should have study drug permanently discontinued. 
Subjects experiencing Grade 4 AEs requiring permanent discontinuation of study drug should be 
followed weekly until resolution or stability of the AE and encouraged to have withdrawal study 
evaluations completed. 
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8.2.1.2.4. Other Management Criteria 
The Medical Monitor should be notified if any of the following occur: 
x Severe signs or symptoms, or significant changes in any of the safety assessments, 
that put the safety of the subject at risk (e.g., laboratory tests or vital signs, etc.) as 
judged by the Investigator 
8.2.2. 
Assigning Causal Relationship to Study Drug 
An Investigator is to make the causality assessment. Causality assessment may only be delegated 
to a Principal Investigator or Sub-Investigator; however, if it is delegated to any other staff, this 
must be recorded as a protocol deviation. The reasonable possibility of the relationship of an 
adverse event to study drug is to be assessed with careful medical consideration at the time of 
evaluation of an adverse event. The following definitions are to be used for the relationship of 
the adverse event to study drug: 
x Related: A clinical event, including laboratory test abnormality, with a temporal 
relationship to study drug administration that makes a causal relationship plausible, 
unlikely attributed to concurrent disease or other drugs or chemicals, and that follows 
a clinically reasonable response on readministration (rechallenge) with or withdrawal 
(dechallenge) from study drug, although information on drug withdrawal may be 
lacking or unclear 
x Not related: A clinical event, including laboratory test abnormality, with a temporal 
relationship to study drug administration that makes a causal relationship improbable 
and/or in which other drugs, chemicals, or underlying disease provide a plausible 
explanation 
Any AEs/SAEs assessed as related to study participation (e.g., protocol-mandated procedures, 
invasive tests, or change in existing therapy) or related to study drug will be collected from the 
time a subject consents to participate in the study up to and including any follow-up contact. 
All AEs, whether related to study drug or not, must be fully and completely documented on the 
AE page of the eCRF and in the subject’s clinical record. In the event a subject is withdrawn 
from the study because of an adverse event, the primary reason for withdrawal (e.g., due to an 
adverse event) must be recorded on the eCRF as such. 
8.3. 
Time Period and Frequency for Event Assessment and Follow-up 
8.3.1. 
Adverse Event Reporting 
All AEs will be collected from the time of signed informed consent until the final visit. 
Any AEs assessed as related to study participation (e.g., protocol-mandated procedures, invasive 
tests, or change in existing therapy) will be collected from the time a subject consented to 
participate in the study up to and including any follow-up contact. 
All SAEs will be recorded in the eCRF and reported to the Sponsor within 24 hours via email or 
phone (refer to Medical Monitor/Sponsor Information page for contact information) 
(see Section 8.4). 
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8.3.2. 
Follow-up of Adverse Events 
After the initial AE/SAE report, the Investigator is required to proactively follow each Subject at 
subsequent visits/contacts. All SAEs and nonserious AEs will be followed until resolution, until 
the condition stabilizes, until the event is otherwise explained, or until the subject is lost to 
follow-up. 
The Investigator will assess the outcome of each AE using the following criteria: 
x Recovered/Resolved: The event has improved or subject recuperated. 
x Recovered/Resolved with sequelae: The subject has recuperated but retained 
pathological conditions resulting from the prior disease or injury. 
x Recovering/Resolving: The event is improving. 
x Not recovered/Not resolved: The event has not improved or subject recuperated. 
x Unknown: The outcome of the event is not known, not observed, not recorded, or 
refused 
x Fatal: Termination of life as an outcome of the AE. 
8.4. 
Reporting Procedures 
8.4.1. 
Serious Adverse Event Reporting 
When an Investigator determines that an AE meets the protocol definition of an SAE during the 
study, he/she must notify the Sponsor using an SAE Report Form within 24 hours of the study 
site personnel’s knowledge of the event, regardless of the Investigator assessment of the 
relationship of the event to study drug. Relevant information will be entered on the AE page and 
on all other applicable pages of the eCRF; source documentation should not be sent with the 
SAE Report Form unless requested. 
Follow-up information received on SAEs, should all be faxed to the Sponsor within 1 business 
day of receipt (refer to Medical Monitor/Sponsor Information page for contact information). This 
information should be included on a follow-up SAE form and placed with the original SAE 
information. 
All SAEs will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the subject is lost to follow-up. 
The completed SAE Report Form should be submitted via email or fax to the SAE Reporting 
Contact which can be found on the Medical Monitor/Sponsor Information Page of this protocol. 
Do not delay reporting a suspected SAE in order to obtain additional information. Any additional 
information, if collected, can be reported as a follow-up to the initial report. 
8.4.2. 
Regulatory Reporting Requirements for Serious Adverse Events 
Prompt notification by the Investigator to the Sponsor of SAEs (even for noninterventional 
postmarketing studies) is essential so that legal obligations and ethical responsibilities towards 
the safety of subjects and the safety of a product under clinical investigation are met. 
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The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation. The Sponsor will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/IEC, and Investigators. 
Investigator safety reports are prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and are forwarded to Investigators as necessary. 
An Investigator who receives an Investigator safety report describing a SAE(s) or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will file it with the 
Investigator’s Brochure and will notify the IRB/IEC, if appropriate, according to local 
requirements. 
8.5. 
Pregnancy Management and Reporting 
Any female subject who becomes pregnant during the study will be withdrawn. Details will be 
collected for all pregnancies in female subjects and female partners of male subjects that begin 
after the start of dosing and through the Follow-up Visit. Pregnancy is not automatically 
considered an AE. 
If a pregnancy is reported, then the Investigator should complete a Pregnancy Report Form and 
submit via email or fax to the Pregnancy Reporting Contact which contact information can be 
found on the Medical Monitor/Sponsor Information Page of this protocol, within 2 weeks of 
learning of the pregnancy. The subject will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to the Sponsor. 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. 
Any premature termination of the pregnancy will be reported. 
Any SAE occurring in association with a pregnancy brought to the Investigator’s attention after 
the subject has completed the study and considered by the Investigator as possibly related to the 
study drug must be promptly reported to the sponsor or the sponsor’s representative. 
The Investigator must attempt to collect pregnancy information on any female partners of male 
study subjects who become pregnant while the subject is enrolled in the study. Pregnancy 
information must be reported to the sponsor or the sponsor’s representative as described above. 
The partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to Sponsor or the Sponsor’s representative. 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. 
Any premature termination of the pregnancy will be reported on the pregnancy report form. 
8.6. 
Safety Oversight 
No independent Data Monitoring Committee will be used for this study; however, the Sponsor 
(including the Medical Monitor) will monitor safety on a periodic basis throughout the study 
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9. 
DATA MANAGEMENT 
For this study, subject data will be entered into Sponsor-approved electronic database and 
combined with data provided from other sources in validated datasets then transmitted 
electronically to the Sponsor or designee. 
Management of clinical data will be performed in accordance with applicable Sponsor approved 
standards and data cleaning procedures to ensure the integrity of the data, e.g., errors will be 
corrected, and inconsistencies clarified. 
Adverse events and relevant medical history will be coded using the most current version of the 
Medical Dictionary for Regulatory Activities (MedDRA). Concomitant medications will be 
coded with the most current version of World Health Organization Drug Global Dictionary 
(WHODrugGlobal). 
The Investigator will retain original source documents and the Sponsor will receive 
eCRF-required data as electronic datasets. Subject initials will not be collected or transmitted to 
the Sponsor. 
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10. 
STATISTICAL CONSIDERATIONS AND DATA ANALYSES 
This study is intended to show that tapinarof cream has a favorable safety and efficacy profile 
during repeated, intermittent treatment courses over an extended period of time. 
10.1. 
General Considerations 
All study data will be summarized overall by treatment group in the pivotal studies using 
descriptive statistics. Categorical variables will be reported using frequency and percentage 
(e.g., gender, race). Continuous variables will be reported using number of subjects, mean, 
standard deviation (SD), median, minimum, and maximum. All safety and efficacy data will be 
listed by subject. 
10.2. 
Determination of Sample Size 
The sample size of this study is based on the ICH E1 guideline on extent of population exposure 
to assess clinical safety for drugs intended for long-term treatment of non-life-threatening 
conditions. An estimated 850 subjects who complete Study DMVT-505-3001 or 
Study DMVT-505-3002 will be enrolled in this study across all regions. A high discontinuation 
rate is anticipated in this long-term extension study. Approximately 300 subjects are expected to 
complete the study (40 weeks of treatment). 
10.3. 
Analysis Populations 
All subjects enrolled into the study will be included in the intent-to-treat (ITT) analysis set. 
10.4. 
Planned Analyses 
All efficacy and safety measures over the course of the study will be presented. All analyses will 
be based on the ITT population. Details of planned analyses will be described in the Statistical 
Analysis Plan (SAP), which will be finalized prior to database lock. 
10.4.1. 
Demographics and Baseline Characteristics 
Demographics and baseline characteristics will be summarized and include frequency and 
percentages for categorical variables and mean, SD, median, minimum, and maximum for 
continuous variables. 
10.4.2. 
Efficacy Analyses 
All efficacy analyses will be performed based on the ITT analysis set as described above. 
Summaries will be presented by original treatment group assigned in the pivotal studies and 
overall. Summaries of efficacy endpoints by visit will be performed using observed cases (OC) 
and last observation carried forward (LOCF) methods. 
Efficacy endpoints are as follows: 
x Proportion of subjects who experience a PGA ≥ 2 at least 1 time in the study and the 
median time from baseline to first worsening (PGA ≥ 2) for subjects entering the 
study with a PGA score of clear (0) 
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Change in disease impact on daily activities, as measured by the subject-reported DLQI total and 
individual dimension scores 
10.4.5. 
Analysis of Patient Satisfaction Questionnaire 
 
Responses for each question of the Patient Satisfaction Questionnaire will be summarized by 
visit. 
10.5. 
Interim Analyses 
A data-cut will be made at the time of preparation of the marketing application to present interim 
results; the final analysis will be conducted after study completion (e.g., the last subject’s last 
visit). 
10.6. 
Handling of Missing Data 
Summaries of efficacy endpoints by visit will be performed using observed cases (OC) and last 
observation carried forward (LOCF) methods. 
 
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11. 
RESPONSIBILITIES 
11.1. 
Investigator Responsibilities 
11.1.1. 
Good Clinical Practice 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
“Declaration of Helsinki” (as amended in Edinburgh, Tokyo, Venice, Hong Kong, and South 
Africa), ICH guidelines, or with the laws and regulations of the country in which the research is 
conducted, whichever affords the greater protection to the study subject. For studies conducted 
under a United States (US) Investigational New Drug Application (IND), the Investigator will 
ensure that the basic principles of “Good Clinical Practice,” as outlined in 21 Code of Federal 
Regulations (CFR) 312, Subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, 
part 50, 1998, and 21 CFR, part 56, 1998, are adhered to. These standards are consistent with the 
requirements of the European Community Directive 2001/20/EC. 
Since this is a “covered” clinical trial, the Investigator will ensure that 21 CFR, Part 54, 1998, is 
adhered to; a “covered” clinical trial is any “study of a drug or device in humans submitted in a 
marketing application or reclassification petition subject to this part that the applicant or Food 
and Drug Administration (FDA) relies on to establish that the product is effective (including 
studies that show equivalence to an effective product) or that make a significant contribution to 
the demonstration of safety.” This requires that Investigators and all sub-investigators must 
provide documentation of their financial interest or arrangements with the Sponsor, or 
proprietary interests in the drug being studied. This documentation must be provided before 
participation of the Investigator and any sub-investigator. The Investigator and sub-investigator 
agree to notify the Sponsor of any change reportable interests during the study and for 1 year 
following completion of the study. Study completion is defined as the date that the last subject 
has completed the protocol defined activities. 
11.1.2. 
Institutional Review Board/Independent Ethics Committee Approval 
This protocol and any accompanying material to be provided to the subject (such as 
advertisements, subject information sheets, or descriptions of the study used to obtain informed 
consent) will be submitted by the Investigator to an IRB or IEC. Approval from the IRB or IEC 
must be obtained before starting the study and should be documented in a letter to the 
Investigator specifying the protocol number, protocol version, protocol date, documents 
reviewed, and date on which the committee met and granted the approval. 
Any modifications made to the protocol after receipt of IRB or IEC approval must also be 
submitted to the IRB or IEC for approval before implementation. 
11.1.3. 
Informed Consent/Assent 
The Investigator is responsible for obtaining written informed consent/assent from each 
individual participating in this study after adequate explanation of the aims, methods, objectives, 
and potential hazards of the study and before undertaking any study-related procedures. The 
Investigator must utilize an IRB or IEC-approved consent form for documenting written 
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informed consent. Each informed consent will be appropriately signed and dated by the Subject 
or the subject’s legally authorized representative and the person obtaining consent. 
11.1.4. 
Confidentiality 
The Investigator must assure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. Only subject number, date of birth, and an 
identification code (e.g., not names) should be recorded on any form or biological sample 
submitted to the Sponsor, IRB or IEC, or laboratory. The Investigator must keep a screening log 
showing codes, names, and addresses for all Subjects screened and for all subjects enrolled in the 
trial. 
The Investigator agrees that all information received from the Sponsor, including but not limited 
to the Investigator’s Brochure, this protocol, eCRFs, the investigational new drug, and any other 
study information, remain the sole and exclusive property of the Sponsor 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 the Sponsor. The Investigator further agrees to take all reasonable 
precautions to prevent the disclosure by any employee or agent of the study site to any third 
party or otherwise into the public domain. 
11.1.5. 
Study Files and Retention of Records 
The Investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least the following 2 categories: (1) Investigator’s study file, and (2) subject 
clinical source documents. 
The Investigator’s study file will contain the protocol/amendments, eCRF and query forms, IRB 
or IEC and governmental approval with correspondence, informed consent, drug records, staff 
curriculum vitae and authorization forms, and other appropriate documents and correspondence. 
The required source data should include the following for each subject: 
x Subject identification (name, date of birth, gender) 
x Documentation that subject meets eligibility criteria, e.g., history, physical 
examination, and confirmation of diagnosis (to support inclusion and exclusion 
criteria) 
x Participation in trial (including trial number) 
x Trial discussed and date of informed consent 
x Dates of all visits 
x Documentation that protocol specific procedures were performed 
x Results of efficacy parameters, as required by the protocol 
x Start and end date (including dose regimen) of trial medication  
(preferably drug dispensing and return should be documented as well) 
x Record of all adverse events and other safety parameters  
(start and end date, and preferably including causality and intensity) 
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x Concomitant medication (including start and end date, dose if relevant; dose changes 
should be motivated) 
x Date of trial completion and reason for early discontinuation, if applicable 
All clinical study documents must be retained by the Investigator until at least 2 years after the 
last approval of a marketing application in an ICH region (e.g., US, Europe, or Japan) and until 
there are no pending or contemplated marketing applications in an ICH region; or, if no 
application is filed or if the application is not approved for such indication, until 2 years after the 
investigation is discontinued and regulatory authorities have been notified. Investigators may be 
required to retain documents longer if required by applicable regulatory requirements 
(e.g., 25 years in Canada), by local regulations, or by an agreement with the Sponsor. The 
Investigator must notify the Sponsor before destroying any clinical study records. 
Should the Investigator wish to assign the study records to another party or move them to another 
location, the Sponsor must be notified in advance. 
If the Investigator cannot guarantee this archiving requirement at the study site for any or all the 
documents, special arrangements must be made between the Investigator and the Sponsor to 
store these in sealed containers outside of the site so that they can be returned sealed to the 
Investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site. 
Biological samples at the conclusion of this study may be retained in storage by the Sponsor for 
a period up to 10 years for purposes of this study. 
11.1.6. 
Electronic Case Report Forms 
For each Subject enrolled, an eCRF must be completed and signed by the Principal Investigator 
or sub-investigator (as appropriate). This also applies to records for those Subjects who fail to 
complete the study. If a subject withdraws from the study, the reason must be noted on the eCRF. 
If a Subject is withdrawn from the study because of a treatment-limiting adverse event, thorough 
efforts should be made to clearly document the outcome. 
11.1.7. 
Drug Accountability 
The Investigator or designee (e.g., pharmacist) is responsible for ensuring adequate 
accountability of all used and unused investigational medicinal product, vehicles, and 
comparators. This includes acknowledgment of receipt of each shipment of study product 
(quantity and condition), subject dispensing records, and returned or destroyed study product. 
Dispensing records will document quantities received from the Sponsor and quantities dispensed 
to subjects, including lot number, date dispensed, subject identifier number, and the initials of the 
person dispensing the medication. 
At study initiation, the monitor will evaluate the site’s procedure for investigational medicinal 
product disposal/destruction in order to ensure that it complies with the Sponsor requirements. 
At the end of the study, following final drug inventory reconciliation by the monitor, the study 
site will dispose of and/or destroy all unused investigational medicinal product supplies, 
including empty containers, according to these procedures. If the site cannot meet the Sponsor’s 
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requirements for disposal, arrangements will be made between the site and the Sponsor or its 
representative for destruction or return of unused investigational medicinal product supplies. 
All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
11.1.8. 
Inspections 
The Investigator should understand that source documents for this trial should be made available 
to appropriately qualified personnel from the Sponsor or its representatives, to IRBs or IECs, or 
to regulatory authority or health authority inspectors. 
11.1.9. 
Protocol Compliance 
The Investigator is responsible for ensuring the study is conducted in accordance with the 
procedures and evaluations described in this protocol. 
11.2. 
Sponsor Responsibilities 
11.2.1. 
Protocol Modifications 
Protocol modifications, except those intended to reduce immediate risk to study subjects, may be 
made only by the Sponsor. All protocol modifications must be submitted to the IRB or IEC and 
regulatory authorities in accordance with local requirements. Approval must be obtained before 
changes can be implemented. 
11.2.2. 
Study Report and Publications 
A clinical study report will be prepared and provided to the regulatory agency(ies). The Sponsor 
will ensure that the report meets the standards set out in the ICH Guideline for Structure and 
Content of Clinical Study Reports (ICH E3). Note that an abbreviated report may be prepared in 
certain cases. 
After conclusion of the study and without prior written approval from Dermavant Sciences 
GmbH, investigators in this study may communicate, orally present, or publish in scientific 
journals or other scholarly media only after the following conditions have been met: 
x The results of the study in their entirety have been publicly disclosed by or with the 
consent of Dermavant Sciences GmbH, in an abstract, manuscript, or presentation 
form 
OR 
x The study has been completed at all study sites for at least 5 years 
No such communication, presentation, or publication will include Dermavant Sciences GmbH, 
confidential information (see Section 11.1.4). 
The Investigator will submit any proposed publication or presentation along with the respective 
scientific journal or presentation forum at least 30 days before submission of the publication or 
presentation. The Investigator will comply with Dermavant Sciences GmbH, request to delete 
references to its confidential information (other than the study results) in any paper or 
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presentation and agrees to withhold publication or presentation for an additional 60 days in order 
to obtain patent protection if deemed necessary. 
11.2.3. 
Posting of Information on Publicly Available Clinical Trial Registers 
Study information from this protocol will be posted on publicly available clinical trial registers 
before enrollment of subjects begins. Results will be posted as required. 
11.3. 
Joint Investigator/Sponsor Responsibilities 
11.3.1. 
Access to Information for Monitoring 
In accordance with ICH Good Clinical Practice guidelines, the study monitor must have direct 
access to the Investigator’s source documentation in order to verify the data recorded in the 
CRFs for consistency. 
The monitor is responsible for routine review of the CRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries on the CRFs. The Investigator agrees to cooperate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved. 
11.3.2. 
Access to Information for Auditing or Inspections 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
Dermavant Sciences GmbH, may conduct a quality assurance audit. 
Authorized representatives of Dermavant Sciences GmbH, a regulatory authority, an IEC or 
an IRB may visit the site to perform audits or inspections, including source data verification. The 
purpose of a Dermavant Sciences GmbH, audit or inspection is to systematically and 
independently examine all study-related activities and documents to determine whether these 
activities were conducted, and data were recorded, analyzed, and accurately reported according 
to the protocol, Good Clinical Practice guidelines of the ICH, and any applicable regulatory 
requirements. The Investigator should contact Dermavant Sciences GmbH immediately if 
contacted by a regulatory agency about an inspection. 
Representatives of regulatory authorities or of the Sponsor may conduct inspections or audits of 
the clinical study. If the Investigator is notified of an inspection by a regulatory authority the 
Investigator agrees to notify the Sponsor Medical Monitor immediately. The Investigator agrees 
to provide to representatives of a regulatory agency or the Sponsor access to records, facilities, 
and personnel for the effective conduct of any inspection or audit. 
11.3.3. 
Study Discontinuation 
The Sponsor reserves the right to terminate the study at any time. Should this be necessary, the 
Sponsor will arrange discontinuation procedures and notify the appropriate regulatory 
authority(ies), IRBs, and IECs. In terminating the study, the Sponsor and the Investigator will 
assure that adequate consideration is given to the protection of the subjects’ interests. 
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12. 
REFERENCES 
Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY Dermatology. Determining the 
minimal clinically important difference and responsiveness of the Dermatology Life Quality 
Index (DLQI): further data.2015;230(1):27-33. 
Cappon GD and Hurtt ME. Developmental toxicity of the kidney. In: Kapp RW and Yyl L, 
editors. Reproductive Toxicology, Target Organ Series, 3rd edition. New York:Informa 
Healthcare, 2010:193-204. 
Frazier KS and Seely JC. Urinary system. In: Sahota PS, Popp JA, Hardisty JF and Gopinath C, 
editors. Toxicologic Pathology: Nonclinical Safety Assessment. CRC Press, 2013:421-84. 
International Conference on Harmonisation, Guideline for the extent of population exposure to 
assess clinical safety for drugs intended for long-term treatment of non-life-threatening 
conditions. 1994. Available at: https://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/ 
Guidelines/Efficacy/E1/Step4/E1_Guideline.pdf. 
Mason AR, Mason J, Cork M, Dooley G, Hancock H. Topical treatments for chronic plaque 
psoriasis. Cochrane Database of Systematic Reviews. 2013;(3):CD005028. doi: 
10.1002/14651858.CD005028.pub3. 
Parisi R, Symmons DPM, Griffiths CEM, Ashcroft DM. Global epidemiology of psoriasis: a 
systematic review of incidence and prevalence. J Invest Dermatol. 2012;133:377-385. 
Zoetis T and Hurtt ME. Species comparison of anatomical and functional renal development. 
Birth Defects Research Part B. 2003;68:111-120. 
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13.
APPENDICES
PHYSICIAN GLOBAL ASSESSMENT
Each assessment should be made as a visual ‘average’ of the severity of all treated areas at the 
time of the assessment. Following the Baseline visit, assessments will be made without reference 
to Baseline state or any other previous scores.
Scoring should not be influenced by extent of lesions, subject symptoms, or impact on subject’s 
quality of life.
Score/Grade
Description
0
Clear
No signs of psoriasis; postinflammatory hyperpigmentation may be present
1
Almost 
clear
No thickening; normal to pink coloration; no to minimal focal scaling
2
Mild
Just detectable to mild thickening; pink to light red coloration; predominantly fine 
scaling
3
Moderate
Clearly distinguishable to moderate thickening; dull to bright red, clearly distinguishable 
erythema; moderate scaling
4
Severe
Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse 
scaling covering almost all or all lesions
Langley RGB, Feldman SR, Nyirady J, van de Kerkhof P, Papavassilis C. The 5-point Investigator’s Global Assessment (IGA) 
Scale: A modified tool for evaluating plaque psoriasis severity in clinical trials. J Dermatolog Treat. 2015;26(1):23-31.
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DERMATOLOGY LIFE QUALITY INDEX (DLQI) AGES 
16 AND UP
The aim of this questionnaire is to measure how much your skin problem has affected your life 
OVER THE LAST WEEK.  Please check one box for each question.
1.
Over the last week, how itchy, sore, painful or stinging has your skin been?
Very much
A lot
A little
Not at all
2.
Over the last week, how embarrassed or self conscious have you been 
because of your skin?
Very much
A lot
A little
Not at all
3.
Over the last week, how much has your skin interfered with you going 
shopping or looking after your home or yard?
Very much
A lot
A little
Not at all
   Not relevant
4.
Over the last week, how much has your skin influenced the clothes you 
wear?
Very much
A lot
A little
Not at all
   Not relevant
5.
Over the last week, how much has your skin affected any social or leisure
activities?
Very much
A lot
A little
Not at all
   Not relevant
6.
Over the last week, how much has your skin made it difficult for you to do 
any sport?
Very much
A lot
A little
Not at all
   Not relevant
7.
Over the last week, has your skin prevented you from working or studying?
Yes
No
   Not relevant
If "No", over the last week how much has your skin been a problem at work
or studying?
A lot
A little
Not at all 
8.
Over the last week, how much has your skin created problems with your 
partner or any of your close friends or relatives? 
Very much
A lot
A little
Not at all
   Not relevant
9.
Over the last week, how much has your skin caused any sexual difficulties?
Very much
A lot
A little
Not at all
   Not relevant
10. Over the last week, how much of a problem has the treatment for your skin 
been, for example by making your home messy, or by taking up time?
Very much
A lot
A little
Not at all
   Not relevant
© AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the 
authors.
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LOCAL TOLERABILITY SCALE ASSESSMENT
At each specified study visit, the investigator (or qualified evaluator) will assess the presence and 
overall degree of irritation at the application sites, according to the 5-point scale. The score will 
ideally represent an ‘average’ across all application sites. To the fullest extent possible, the same 
investigator (or designated evaluator) will perform all tolerability assessments for an individual 
subject throughout the study.
If the subject is applying study treatment to “sensitive areas” (e.g., genitals, face, neck, and skin folds), 
then also assess the degree of irritation for these areas.
Local Tolerability – Dryness, Erythema, and Peeling
Score
Severity
Description
0
No irritation
No evidence of local irritation/intolerance
1
Mild
Minimal erythema and/or edema, slight glazed appearance
2
Moderate
Definite erythema and/or edema with peeling and/or cracking but does not require 
treatment modification
3
Severe
Erythema, edema glazing with fissures, few vesicles or papules
4
Very Severe 
Strong reaction spreading beyond the treated area, bullous reaction, erosions
At each specified study visit, the subject will use a 5-point tolerability scale to assess the 
presence and degree of burning/stinging and itching at the treatment areas. The score will ideally 
represent an ‘average’ across all application sites.
Local Tolerability – Burning/Stinging and Itching
Score
Severity
Description
0
None
Normal, no discomfort
1
Slight
An awareness, but no discomfort and no intervention required
2
Mild
A noticeable discomfort that causes intermittent awareness
3
Moderate
A noticeable discomfort that causes intermittent awareness and interferes occasionally
with normal daily activities
4
Strong/Severe
A definite continuous discomfort that interferes with normal daily activities
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PATIENT SATISFACTION QUESTIONNAIRE
You are being asked the below questions to better understand how you feel about the cream 
medication (study drug) you used to treat your psoriasis in this study and how it compares to 
other medications you have used to treat your psoriasis in the past.  When answering each 
question, think about the cream medication (study drug) that you have been using as a patient in 
this study.  Please circle the answer that most closely matches how you feel.  
1.
I can easily manage my psoriasis with the study drug 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
2.
The time spent applying the study drug every day was acceptable and did not affect my 
everyday life 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
3.
I am satisfied with how well the study drug worked for my psoriasis
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
4.
I have confidence in the study drug 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
5.
The study drug cleared my skin and kept my psoriasis from coming back 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
6.
If the study drug was available by prescription, I would recommend it to other patients with 
psoriasis
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
7.
If the study drug was available by a prescription, I would use it again or continue on it
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
8.
The study drug is easy to apply
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
9.
The study drug is not greasy 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
10. The study drug quickly absorbs into my skin 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
11. The study drug feels good on my skin 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
12. I am satisfied with the look and feel of the study drug 
Strongly Agree
Agree
Neutral
Disagree 
Strongly Disagree
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The below questions # 13-18 are comparing the study drug to other drugs you have used to treat your 
psoriasis in the past.  When answering these questions, think about how this study drug compares to 
those other drugs you have used.   
 
A topical drug is a drug that is applied to the skin like creams, ointments, lotions, gels, foams, sprays.  
A systemic drug is a drug that is taken by mouth like a capsule or tablet or injected through the skin 
with a needle like a shot or through a vein by a healthcare practitioner.   
 
Have you used other topical drugs to treat your psoriasis in the past?  Yes/no.  If yes, please answer 
questions 13-15.  If no, please go to question 16.   
13. The study drug is more effective than other topical drugs I have used to treat my psoriasis  
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
14. The study drug is easier to use than other topical drugs I have used to treat my psoriasis 
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
15. I prefer the study drug to other topical drugs I have used to treat my psoriasis   
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
Have you used systemic drugs to treat your psoriasis in the past?  Yes/no.  If yes, please answer the 
following questions.  If no, that is the end of the questionnaire.   
16. The study drug is more effective than systemic drugs I have used to treat my psoriasis 
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
17. The study drug is easier to use than systemic drugs I have used to treat my psoriasis  
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
18. I prefer the study drug to systemic drugs I have used to treat my psoriasis 
Strongly Agree  
Agree  
Neutral  
Disagree  
Strongly Disagree 
 
Thank you very much for your participation in this clinical study and questionnaire.   
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PROTOCOL AMENDMENT SUMMARY OF CHANGES
The protocol has been updated with the following changes.  Edits to the protocol are shown in 
bold.
ABBREVIATIONS
Added LOCF (Last Observation Carried Forward). Added OC (Observed Cases); Updated 
WHODrugGlobal to WHO (World Health Organization)
SYNOPSIS
Added statement on use of rescue medication.
Inclusion criteria: revised contraception language for clarity.
The following efficacy study endpoints were added: 
x
Proportion of subjects who experience a PGA ≥ 2 at least 1 time in the study and the 
median time from baseline to first worsening (PGA ≥ 2) for subjects entering the study 
with a PGA score of clear (0)
x
Proportion of subjects who achieve a PGA score of 0 at least 1 time in the study and the 
median time from baseline to first achieving a PGA score of 0 for subjects entering the 
study with a PGA score ≥ 1
x
Duration of each treatment episode, defined as time from each treatment initiation/re-
initiation to each subsequent treatment success (PGA score of 0).
x
Duration of each treatment success (PGA score of 0) to each subsequent worsening (PGA 
≥ 2)
x
Proportion of subjects who never achieve a PGA ≥ 2 throughout the study
x
Proportion of subjects who never achieve a PGA score of 0 or 1 throughout the study
x
Proportion of subjects who never achieve a PGA score of 0 throughout the study
x
PGA scores by visit (OC and LOCF)
x
Change and percent change from baseline in %BSA affected by visit (OC and LOCF)
x
Change and percent change in PASI score by visit (OC and LOCF)
The following study endpoints were deleted: 
x
Median time from each treatment success (PGA 0 or 1) to each subsequent worsening 
(PGA ≥ 2)
x
Proportion of subjects who have a PGA score of clear (0) after treatment
x
Proportion of subjects who have a PGA score of clear (0) or almost clear (1) after 
treatment
x
Proportion of subjects who do not experience disease worsening (PGA ≥ 2)
x
Change over time in percent of %BSA affected
x
Mean duration of each treatment course
x
Percent change over time in PASI score
The statistical method section was updated for clarification as follows: 
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All study data will be summarized overall and by treatment group in the pivotal studies using 
descriptive statistics using the intent-to-treat (ITT) analysis set of subjects.   
The Kaplan-Meier product limit method will be used to estimate the median time (if estimable) 
from baseline to first disease worsening and first disease success (PGA≥2).   
 
Duplicative section of Duration of Treatment was deleted 
Table 1. Schedule of Assessment 
Addition of clinical photography, as applicable at Visits 1-11. Removal of diary and study drug 
assessments for phone call check at Week 2.  Removal of study drug application at the last visit 
(Week 40). Correction of footnote on disease worsening. LTS assessments completed by 
Investigator and Subject were removed for the Baseline Visit (Visit 1). Footnote i. was updated 
to include: This assessment is only required to be completed if the subject was applying study 
drug. Update to footnotes g-m to accommodate photography addition. Added Patient Satisfaction 
Questionnaire at Visit 11. 
Section 1.1 Background Information 
Correction made to reflect language in study report; “contact dermatitis” changed to “dermatitis 
contact.” 
The most frequently reported (1% to 6% of 235 subjects) dermatological adverse events (AEs), 
regardless of causality, were application site discoloration/hyperpigmentation, application site 
dermatitis, papular rash, pruritus, contact dermatitis contact, folliculitis, erythema, and skin 
burning sensation.   
Section 1.3.1.2. Clarification on study design added; 
In the open-label PK Study 201851 with BID dosing of Formulation F of tapinarof cream 
(n=11), 1% and 2%, headache was the most frequently reported during the study (reported for 
100% and 60% of subjects at the 1% and 2% doses, respectively). 
Corrected typographical error: To mitigate potential systemic risks, subjects will be monitored 
for AEs and any abnormal vital signs, physical examination, and laboratory test results.  
Section 2. Objectives and Endpoints 
The following safety and tolerability endpoint was added to this section for consistency with 
other sections within this protocol: Mean scores by visit from LTS 
The following efficacy endpoints were added: 
x Proportion of subjects who experience a PGA ≥ 2 at least 1 time in the study and the 
median time from baseline to first worsening (PGA ≥ 2) for subjects entering the study 
with a PGA score of clear (0) 
x Proportion of subjects who achieve a PGA score of 0 at least 1 time in the study and the 
median time from baseline to first achieving a PGA score of 0 for subjects entering the 
study with a PGA score ≥ 1 
x Duration of each treatment episode, defined as time from each treatment initiation/re-
initiation to each subsequent treatment success (PGA score of 0). 
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x Duration of each treatment success (PGA score of 0) to each subsequent worsening (PGA 
≥ 2) 
x Proportion of subjects who never achieve a PGA ≥ 2 throughout the study 
x Proportion of subjects who never achieve a PGA score of 0 or 1 throughout the study 
x Proportion of subjects who never achieve a PGA score of 0 throughout the study 
x PGA scores by visit (OC and LOCF) 
x Change and percent change from baseline in %BSA affected by visit (OC and LOCF) 
x Change and percent change in PASI score by visit (OC and LOCF) 
x Change in disease impact on daily activities, as measured by the DLQI total and 
individual dimension scores 
 The following study endpoints were deleted:  
• 
Median time from each treatment success (PGA 0 or 1) to each subsequent worsening 
(PGA ≥ 2) 
• 
Proportion of subjects who have a PGA score of clear (0) after treatment 
• 
Proportion of subjects who have a PGA score of clear (0) or almost clear (1) after 
treatment 
• 
Proportion of subjects who do not experience disease worsening (PGA ≥ 2) 
• 
Change over time in percent of %BSA affected 
• 
Mean duration of each treatment course 
• 
Percent change over time in PASI score 
Section 3.1 Overall Design 
Clarified wording around time of dosing each day and protocol violations which is further 
addressed in Section 5.1.5 (Administration of Study Drug) 
Added statement on use of rescue medication. 
Section 4.2 Inclusion Criteria 
Revised contraception language for clarity. 
Section 5.1.5.  Administration of Study Drug 
Provided clarification on application to affected areas for those entering with a PGA score of 0 or 
> 0. 
Added clarification wording around missed doses and protocol deviations: “If a subject misses a 
daily dose, it will be recorded as a protocol deviation. The subject should continue dosing 
the next day and should not apply more than once daily to make up for the missed dose on 
the previous day.” 
Section 5.4 
Clarified that unopened tubes may only be dispensed one time. 
Section 5.6 Prior and Concomitant Therapy 
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Clinical Study Protocol  
 
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Removed wording on collection of concomitant medication for 30 days prior to the baseline visit 
as these medications will already being collected as part of the prior pivotal study. 
Section 6.2.1.1. Physician Global Assessment 
Corrected typographical error: higher PGA scores represent more severe disease.  
Section 6.2.2.2 patient Satisfaction Questionnaire 
Added that subjects will complete the Patient Satisfaction Questionnaire and referenced 
Appendix 5. 
Section 6.2.3. Optional Clinical Photography 
Clinical photography may be performed in a subgroup of subjects at selected study centers that 
participated in photography in the pivotal study. This is not required of subjects for participation 
in the study. Informed consent and photographic release will be required. The photographs may 
not be referred to by the Investigator at any subsequent study visit for the purposes of grading. 
Photographs will be taken of a representative area of the subject’s disease area at the time points 
specified in the Schedule of Assessments (Table 1; see also section 7). Three photographs of the 
selected skin area will be taken in a standardized fashion (ie, same camera, angle, background, 
distance). Procedures for the clinical photography will be contained in the Photography Manual. 
Section 6.3.5 Local Tolerability Scale 
Clarified that the LTS will only be completed by those subjects who are receiving study drug. 
Section 7.1 Visit 1; Baseline 
Added photography of a representative area of the subject’s disease area (optional; at a 
subsection of study centers) (last assessment from pivotal study) 
Removed LTS (last assessment from parent study) 
Section 7.2 Visits 2 to 101; Treatment Period  
The title of the section was updated to accurately reflect the visits. Added Photography of a 
representative area of the subject’s disease area (optional; at a subsection of study centers)   
Section 7.3 Visit 11  
This section was added, as the Patient Satisfaction Questionnaire is now included.  
Section 7.4 Phone Contact at Week 2 (Day 15±3 Days) 
The title of this section was renumbered to Section 7.5 
Section 7.5 Unscheduled Visits 
The title of this section was renumbered to Section 7.6. Added photography of a representative 
area of the subject’s disease area (optional; at a subsection of study centers). Correction made to 
remove the requirement for a study visit. “If disease worsening is confirmed, a new treatment 
course will be initiated, and the subject will be scheduled to return to the study site after 2 
weeks.” 
Section 7.6 Early Termination  
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The title of this section was renumbered to Section 7.7. Added the Patient Satisfaction 
Questionnaire.  
Section 7.7 End of Study  
The title of this section was renumbered to Section 7.8.  
Section 8.1.1. Definition of Adverse Events 
To avoid confusion, the wording that defines local adverse events has been edited since 
“evaluation of local tolerability” is being assessed with a specific scale (Appendix 8). 
Section 8.1.3. Adverse Events of Special Interest 
Changed wording to state that “study drug will may be discontinued, and study drug may be 
restarted when event resolves”, if a subject has an adverse event of special interest 
Section 8.2.2 Assigning Causal Relationship to Study Drug 
Updated to allow Principal Investigator to delegate causality assessment to sub-Investigators. 
Changed wording to state that “Causality assessment may only be delegated to a Principal 
Investigator or Sub-Investigator;” 
Section 10.4.2. Efficacy Analyses 
Updated with revised efficacy endpoints described in the synopsis and Section 2. 
Section 10.4.5. Analysis of Patient Satisfaction Questionnaire 
Statistical analysis of the Patient Satisfaction Questionnaire was added. 
Section 10.6 Handling of Missing Data 
Section updated as follows: Missing data will not be imputed. Summaries of efficacy endpoints 
by visit will be performed using observed cases (OC) and last observation carried forward 
(LOCF) methods. 
Appendix 3, page 75. CALCULATION of BSA and PASI 
Clarification of body surface area calculation and correction in table for calculation of PASI; 
score of 0 changed from 1% to 0% skin covered with psoriasis and score of 1 changed from 1 - 
<10% to <10% consistent with published paper (Feldman Feldman SR, Krueger GG. Psoriasis 
assessment tools in clinical trials. Ann Rheum Dis.2005;64 (suppl II):ii65-ii68.) 
 
Percentage of skin covered with psoriasis for each of the 4 areas 
Affected  
0% 
< 10% 
10 - < 30% 
30 - < 50% 
50 - < 70% 
70 - < 90% 
≥ 90% 
Score 
0 
1 
2 
3 
4 
5 
6 
In addition, the Area Score has been shaded and will be auto-calculated in the eCRF. 
Appendix 5. Patient Satisfaction Questionnaire  
New appendix added with example questions. 
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SAP_001.pdf: 
Protocol No. DMVT-505-3003
IQVIA Biotech Study No. GZA92798
A LONG-TERM, OPEN-LABEL, EXTENSION STUDY TO EVALUATE THE SAFETY
AND EFFICACY OF TAPINAROF CREAM, 1% FOR THE TREATMENT OF PLAQUE
PSORIASIS IN ADULTS
Statistical Analysis Plan Amendment 2, version 3.0
Document last saved: 16-Nov-2020 8:25 PM


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Revision History
Date
Reason for update
Section Updated
21FEB2020
Original Version 1.0
NA
15JUN2020
Amendment 1
Version 2.0
Section 11.4 Study Medication and Exposure
Compliance
o
Updated the calculation for average grams of 
study drug administered per doses
administered. 
Section 11.7 Efficacy endpoint
o
Added PASI-50, PASI-75, PASI-90 analysis
Added Section 11.12 Additional Analyses – COVID-
19
Removed Section 11.11.5 Physical Examination
Section 12 Change from the protocol and planned 
analyses
o
Clarified additional analyses added due to 
COVID-19
16NOV2020
Amendment 2
Version 3.0
Section 8 Handling of missing data
o
Clarified Visit 1 date instead of first dose date 
will be used in imputation rule of AE dates
Section 10.4 Baseline and change from baseline
o
Updated baseline definition
Section 11.1 Subject disposition
o
Updated definition of number of days in the 
study
Section 11.4 Study medication exposure and 
compliance
o
Updated exposure parameter definition 
Section 11.7 Efficacy endpoints
o
Updated definition of time to achieving PGA 
score of 0, duration of treatment episodes, 
duration of treatment successes
Section 11.11.1 Adverse events
o
Updated treatment-emergent AE definition
o
Added a listing for AEs resolved prior to the 
Visit 1 date
o
Added additional TEAE summaries


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Table of Contents
Revision History.............................................................................................................................2
Table of Contents...........................................................................................................................3
List of Abbreviations and Definitions of Terms..........................................................................5
1.
INTRODUCTION..................................................................................................................6
2.
STUDY OBJECTIVES..........................................................................................................6
3.
STUDY DESIGN....................................................................................................................6
4.
HARDWARE AND SOFTWARE........................................................................................7
5.
DATABASE CLOSURE .......................................................................................................7
6.
SAMPLE SIZE DETERMINATION...................................................................................7
7.
ANALYSIS POPULATIONS ...............................................................................................7
8.
HANDLING OF MISSING DATA ......................................................................................8
9.
INTERIM ANALYSIS ..........................................................................................................8
10. DATA CONVENTIONS FOR ANALYSIS.........................................................................9
10.1
General Statistical Principles.........................................................................................9
10.2
Pooling of Study Sites....................................................................................................9
10.3
Study Day.......................................................................................................................9
10.4
Baseline and Change from Baseline ..............................................................................9
10.5
Analysis Visit Window..................................................................................................9
10.6
Multiple Comparisons..................................................................................................10
11. STATISTICAL EVALUATION.........................................................................................10
11.1
Subject Disposition......................................................................................................10
11.2
Protocol Deviation .......................................................................................................10
11.3
Demographic and Baseline Characteristics .................................................................10
11.4
Study Medication Exposure and Compliance..............................................................11
11.5
Prior and Concomitant Medications ............................................................................12
11.6
Medical History and Concurrent Procedures...............................................................12
11.7
Efficacy Endpoints.......................................................................................................12
11.8
Efficacy Analyses ........................................................................................................13
11.9
Health-related Quality of Life......................................................................................14
11.10 Patient Satisfaction Questionnaire...............................................................................16
11.11 Safety Analysis ............................................................................................................16


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11.11.1 Adverse Events ................................................................................................16
11.11.2Local Tolerability Scale (LTS) ........................................................................18
11.11.3Clinical Laboratory Testing.............................................................................18
11.11.4 Vital Signs........................................................................................................19
11.12 Additional Analyses – COVID-19...............................................................................19
12. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES.........................19
13. HEADINGS ..........................................................................................................................20
14. ARCHIVING AND RETENTION OF DOCUMENTS....................................................20
15. OUTLINE OF PROPOSED TABLES, LISTINGS AND FIGURES..............................20


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List of Abbreviations and Definitions of Terms
Abbreviation
Definition
ADaM
Analysis dataset model
AE
Adverse event
AESI
Adverse event of special interest
ATC
Anatomical Therapeutic Chemical Classification System
BMI
Body mass index
BSA
Body surface area
COVID-19
Coronavirus Disease 2019
DLQI
Dermatology Life Quality Index
eCRF
Electronic Case Report Form
EOS
End of study
ITT
Intent-to-Treat
LOCF
Last Observation Carried Forward
LTS
Local Tolerability Scale
MedDRA
Medical Dictionary for Regulatory Activities
OC
Observed Cases
ODS
Output Delivery System
PASI
Psoriasis Area and Severity Index
PGA
Physician’s Global Assessment
PT
Preferred Term
QoL
Quality of Life
RTF
Rich-text-formatted
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Standard deviation
SDTM
Study data tabulation model
SOC
System Organ Class
TEAE
Treatment-emergent adverse event
WHO-DD
World Health Organization – Drug Dictionary


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1. INTRODUCTION
This Statistical Analysis Plan (SAP), based on the study Protocol Amendment 1 (Version 1.0)
dated December 16, 2019, provides additional details concerning the statistical analyses outlined 
in the protocol and will reflect all changes to the protocol from all amendments. This plan will 
not repeat all the definitions given in the protocol but will provide further details of the 
summaries and analyses planned therein. 
2. STUDY OBJECTIVES
The objectives of this study are as follows:
To evaluate the safety and tolerability of tapinarof cream, 1% in adults with plaque 
psoriasis
To describe the efficacy of tapinarof cream, 1% over an extended period of time in adults
with plaque psoriasis
To describe the effect of tapinarof cream, 1% on psoriasis symptom severity and the 
associated impact on daily activities and attitudes in adults with plaque psoriasis
3. STUDY DESIGN
This is a long-term, open-label, multicenter, study to evaluate the safety and efficacy of topical
tapinarof cream, 1% in adults with plaque psoriasis. Subjects in this study completed treatment
with tapinarof or
vehicle in 1 of 2 pivotal
Phase 3
efficacy and safety studies
(Study DMVT-505-3001 or Study DMVT-505-3002). The study consists of up to 40 weeks of 
treatment and a 4-week safety follow-up period.
At the completion of the Week-12 Visit of the pivotal study (Visit 1, Baseline [Day 1] in this
study), eligibility of the subjects opting to enroll in this extension study is confirmed. Study 
visits during the treatment period occur every 4 weeks (±3 days). A Phone Call is performed at 
Week 2 (Day 15).  Unscheduled visits occur, as needed. Subjects who withdraw from the study 
before Week 40 return to the study center for an Early Termination Visit. The total duration of 
study participation is approximately 44 weeks.
At the start of the study, subjects entering with a PGA
1 receive treatment with tapinarof 
cream, 1% until they achieve a PGA score of 0, at which time treatment is discontinued and 
subjects are monitored for durability of response. If/when disease worsening occurs, as
evidenced by a P
then be re-initiated and continued until a PGA of 0 is 
observed. 
Subjects entering with a PGA of 0 will have treatment discontinued and they will be monitored 
for durability of response. If/when disease worsening occurs, as evidenc
treatment is re-initiated and continued until a PGA of 0 is observed.
The pattern of treatment, suspension and re-treatment is continued until the Week 40 visit.
Study drug dispensed to subjects during the clinic visits is applied once daily to all affected 
areas, including newly appearing lesions and lesions that improve during the study. Subjects 


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apply sufficient study drug to cover completely each lesion with a thin layer of study drug and
record the time of study drug application in a daily diary provided by the study site. Subjects 
may treat fingernails, toenails, palms, soles, and scalp lesions with study drug; however,
improvement of psoriasis is not assessed in these areas.
Safety assessments include AEs, local (application site) tolerability, clinical laboratory tests, vital 
signs, physical examinations, and investigator-assessed LTS. Efficacy assessments include a 
5-point static PGA (0-4 scale), %BSA affected, the PASI, and subject-reported DLQI.
A subject is considered to have completed the study when he/she completes all required 
procedures/visits for the 40-week (Visit 11) treatment period. The end of the study is defined as 
when the last active subject has completed the Follow-up Visit.
4. HARDWARE AND SOFTWARE
Statistical analysis will be performed following IQVIA Biotech standard operating procedures 
and on the IQVIA Biotech computer network. All statistical analysis will be performed using 
SAS Version 9.4 or greater with program code prepared specifically for the project by qualified 
IQVIA Biotech statisticians and SAS programmers.
The SAS programs will generate rich-text-formatted (RTF) output with the “RTF” extension 
using the SAS (ODS). Datasets will be created and taken as input to validated SAS programs to
generate the report-ready tables, listings, and figures. Each output display will show the names of 
the data sets and SAS program used to produce it.
5. DATABASE CLOSURE
After completion of all data review procedures, validation of the project database, and approval 
of the data review document by the study sponsor, the clinical database will be closed. Any 
change to the clinical database after this time will require written authorization, with explanation, 
by the Sponsor and the Biostatistician.
6. SAMPLE SIZE DETERMINATION
The sample size of this study is based on the ICH E1 guideline on extent of population exposure
to assess clinical safety for drugs intended for long-term treatment of non-life-threatening 
conditions. An estimated 850 subjects who complete Study DMVT-505-3001 or Study DMVT-
505-3002 will be enrolled in this study at approximately 100 to 120 study sites in the US and 
Canada. A high discontinuation rate is anticipated in this long-term extension study. 
Approximately 300 subjects are expected to complete the study (40 weeks of treatment).
7. ANALYSIS POPULATIONS
Intent-To-Treat (ITT) Analysis Set: includes all subjects enrolled into the study. All subjects 
who signed the informed consent will have enrolled in the study. All efficacy and safety analysis
will be performed over ITT analysis set.


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Subjects will be analyzed overall and by the original treatment assigned in pivotal studies
(DMVT-505-3001 and DMVT-505-3002). This will be referred to below as DB (double-blind)
treatment group.
8. HANDLING OF MISSING DATA 
Efficacy endpoints will be summarized by visit using observed cases (OC) and last observation 
carried forward (LOCF) methods as appropriate. Baseline values will not be carried forward.
Imputation of Start and End Dates of Adverse Event (AE)
To calculate duration of Adverse Events, the following rules will be used where applicable to 
impute partial or completely missing start dates or end dates:
If only the day is missing for a start date, the 1st of the month will be imputed. If the new 
estimated date falls before the Visit 1 date, while the known month and year match the 
month and year of the Visit 1 date, the date of Visit 1 will be used as the new estimated 
date. 
If only the day is missing for an end date, the last day of the month will be imputed. If the 
new estimated date falls after the date of last study visit, the date of last study visit will be 
used as the new estimated date.
If both the day and the month are missing for a start date or end date, no imputation will 
be used, and the duration will not be calculated. 
If the start date or end date is completely missing, duration will not be calculated. 
For AEs ongoing at the end of pivotal studies, duration will be computed using the DMVT-505-
3003 visit 1 date as the AE start date.
If relationship of AE to treatment is missing, the event will be conservatively considered as being 
related to study drug. Missing AE severity will be imputed to the highest severity level (most 
severe). Through the data cleaning process, all attempts will be made to avoid missing values for 
relationship and severity.  
9. INTERIM ANALYSIS
A data-cut will be made at the time of preparation of the marketing application to present interim 
results, Guidance ICH-E1A suggests that at such time, 100 tapinarof subjects should have
completed 52 weeks of treatment and 300 tapinarof subjects should have completed 26 weeks of 
treatment exposure combined over the pivotal studies and the current study. The final analysis 
will be conducted after study completion (e.g., the last participant’s last visit).


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10.DATA CONVENTIONS FOR ANALYSIS
10.1
General Statistical Principles
The study efficacy and safety results will be summarized descriptively.
There will be no
statistical testing.
All observed and derived variables (e.g., change from baseline, percentage change from baseline, 
and response status) that are summarized will be presented in by-subject listings. Unless 
otherwise noted, the data will be sorted by DB treatment group and subject number and then by 
date within subject number.
For categorical parameters, the number and percentage of subjects in each category will be 
presented. The denominators for percentages will be the number of subjects appropriate for the
purpose. For continuous parameters, descriptive statistics will include number of subjects, mean, 
standard deviation (SD), median, minimum, and maximum.
10.2
Pooling of Study Sites
No by-site summaries are planned.
10.3
Study Day
Day 1 is the date of Visit 1 (which is also the last visit in pivotal studies). Study day is calculated
relative to the date of Day 1.
10.4
Baseline and Change from Baseline
For PGA score and % BSA Affected, baseline is defined as the assessment collected at Visit 1 in 
the extension study. If Visit 1 measurement is missing, the baseline value will be considered as 
missing. 
For all other efficacy and safety assessments (PASI, DLQI, vital signs and laboratory results), 
baseline is defined as the last available measurement on or after Week 12 visit date in pivotal 
studies and on or before the Visit 1 visit date in the extension study. If there’s no measurement 
available during this time period, the baseline value will be considered as missing. Change from 
baseline is the post-baseline value minus baseline unless otherwise specified. Percent change
from baseline is (Change from baseline / baseline) * 100%.
10.5
Analysis Visit Window
Efficacy and safety endpoints will be summarized according to the nominal visit as assigned by 
the investigator except for assessments collected on early termination visits. Early termination 
visit will be re-numbered to the last nominal visit number + 1. For example, if a subject attended 
Visit 1, Visit 2 (Week 4), Visit 3 (Week 8) and then early terminated, the early termination visit 
will be re-numbered and analyzed as Visit 4 (Week 12). 


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Unscheduled visits will not be re-numbered and will not be included in table summaries. They 
will only be listed.
10.6
Multiple Comparisons
Does not apply.
11.STATISTICAL EVALUATION 
11.1
Subject Disposition
Subjects who enroll (ITT population), who apply any study medication, who complete the study
and who withdraw from the study (together with the reasons for withdrawal) will be summarized
by counts and percentages. Subjects for whom drug was permanently withdrawn or interrupted 
due to AE, PGA score or other reasons will also be summarized by counts and percentages, over 
the entire study and by visit.
Counts will be presented overall and by DB treatment group. Listings by subject will document 
enrollment and disposition.
The number of days in the study, defined as date of study completion / discontinuation (or date 
of last visit if the study completion/discontinuation date is missing) minus date of Visit 1 plus 1,
will be summarized using descriptive statistics overall and by DB treatment group. A figure with
Kaplan-Meier curves will also be generated to illustrate this information.
11.2
Protocol Deviation
Protocol deviations will be listed by subject. Protocol deviation categories will be summarized 
overall and by DB treatment group.
11.3
Demographic and Baseline Characteristics
Demographics and baseline characteristics will be summarized overall and by DB treatment 
group over the ITT population. The following demographic (as collected in pivotal studies) and 
baseline variables will be included:
Age (years)
Gender 
Race
Ethnicity
Weight (kg)
Height (cm)
BMI (kg/m2)
Baseline PGA – current study and pivotal study
Baseline PASI score – current study and pivotal study
Baseline %BSA Affected – current study and pivotal study


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11.4
Study Medication Exposure and Compliance
Subjects will be characterized by a series of treatment episodes as defined in Section 11.7. These 
treatment episode definitions are based on attainment of specified PGA values.  
The following exposure and compliance parameters will be summarized descriptively over the
overall span of treatment episodes, overall and by DB treatment group:
Total expected number of days exposed, calculated as the sum of number of days over all 
treatment episodes.
Total number of doses administered within treatment episodes, calculated from the 
subject dose diary and summed over all treatment episodes. If a subject does not return 
diary or returns the diary with missing dosing record, the number of doses taken during 
that period is assumed to be 0.
Grams (g) of study drug administered within treatment episodes, total will be summed 
over all treatment episodes. Drug administered is calculated as the summation of the
difference between dispensed weight and returned weight for all returned tubes. 
Unreturned tubes will be assumed unused and will be included as 0 gram in amount drug
used calculation. Average grams of study drug administered per expected day exposed 
and per doses administered will be calculated as the total grams / total number of days 
exposure (or total number of doses administered). Subjects with more than 1-day
exposure but had no diaries returned will not have average grams per doses administered 
reported.
Percent compliance will be calculated as the total number of doses administered within 
treatment episodes over the total expected number of days exposed.
Subject compliance,
compliance over the entire duration of study. If the
percentage of study medication compliance is unknown, the subject is assumed to be non-
compliant with study medication.
In addition, the following exposure parameters will be summarized descriptively for the entire 
study (regardless of PGA status) overall and by DB treatment group:
Total number of doses administered, calculated from the subject dose diary and in-clinic 
dosing. If a subject does not return diary or returns the diary with missing dosing record, 
the number of doses taken during that period is assumed to be 0.  
Grams (g) of study drug administered. Drug administered is calculated as the summation 
of the difference between dispensed weight and returned weight for all returned tubes. 
Unreturned tubes will be assumed unused and will be included as 0 gram in amount drug 
used calculation. Average grams of study drug administered per doses administered will 


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be calculated as the total grams / total number of doses administered. Subjects that had no 
diaries returned will not have average grams per doses administered reported.
11.5
Prior and Concomitant Medications
Prior (within 30 days before Visit 1 and with stop dates prior to Visit 1) medications would have
been captured in the pivotal studies and will not be presented in this study.
Concomitant (ongoing or with stop dates on or after Visit 1) medications will be listed by 
subject. If the medication is ongoing or the stop year is missing, the medication will be 
considered as received for the entire duration of the study. Concomitant medications that are
ongoing as of the end of the pivotal studies will be displayed in a separate listing.
Medications will be coded using WHO-DD terminology. Concomitant medications will be 
summarized by WHO-DD Anatomical-Therapeutic-Chemical (ATC) classification and preferred 
term (PT), overall and by DB treatment group.
11.6
Medical History and Concurrent Procedures
Medical history (including previous and ongoing medical conditions) collected during the pivotal
studies will be coded using MedDRA and listed by subject. Medical history will be summarized 
by system organ class (SOC) and PT, overall and by DB treatment group.
11.7
Efficacy Endpoints
Efficacy endpoints are as follows:
For subjects entering the study with a PGA score of clear (0): 
Proportion of subjects who experience
at least 1 time during the study.
Proportion of subjects who never experience
throughout the study.
Time to first worsening (
), defined as days from date of Visit 1 date to the date 
2. Subjects who never experience
throughout the 
study will be censored at the date of their last PGA assessment.
For subjects entering the study
1:
Proportions of subjects who achieve PGA = 0 at least 1 time during the study 
 
For subjects entering the study
2:


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Proportions of subjects who achieved PGA = 0 or 1 at least 1 time during the study.
Proportions of subjects who never achieve PGA = 0 or 1 throughout the study.
The following endpoints will be summarized over subjects in ITT population:
Duration (days) of treatment episodes, defined as time (days) from the date of each PGA 
2 (or PGA 
1 for the first episode) to 1 day before each subsequent treatment success 
(PGA = 0). The date of the last PGA assessment will be used as the end date for episodes 
ongoing at the end of the study.
 
 
 
 
 
 
 
 
 
 
change and percent change from baseline in %BSA affected by visit
(OC and LOCF).
 change and percent change from baseline in PASI score by visit (OC 
and LOCF)
 
 
 
 
 
 
11.8
Efficacy Analyses
All efficacy parameters will be summarized over the ITT analysis set overall and by DB 
treatment group.
Summaries of efficacy endpoints by visit will be performed using OC and 
LOCF methods.


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Time to event parameters, such as the time from treatment success to subsequent worsening
(PGA 
2) or duration of treatment episode, will be summarized by the Kaplan-Meier product 
limit method using OC.
Median time to event will be estimated.
If the median time is not 
determined, other percentiles will be estimated. 
The remaining efficacy endpoints will be summarized descriptively as follows: continuous data 
will include the mean, SD, minimum, maximum, median, and number of observations; 
descriptive summary statistics for categorical data will include frequency counts and 
percentages.
For the following efficacy outcomes:
1. Proportions of subjects who achieve PGA = 0 at least 1 time during the study (for 
subjects entering the study
1):
2. Proportions of subjects who experienced PGA 
2 at least 1 time during the study (for 
subjects entering the study with a PGA score = 0):
3. PGA scores at Week 40 (LOCF)
4. BSA
 change from baseline to Week 40 (LOCF)
5. PASI 
 change from baseline to Week 40 (LOCF)
subgroup analyses will be generated for the following groupings:
Baseline PGA
Age (<65 and >= 65 years old)
Sex 
Race (White, Other)
Baseline % BSA affected – (<10%,
10%)
Duration of disease (<5 years, 5-10 years, >10 years)
Country (USA and Canada)
11.9
Health-related Quality of Life
The DLQI was assessed at 4-week intervals to measure the impact of tapinarof cream, 1% on 
quality of life in adults with plaque psoriasis.:
The DLQI is a 10-item PRO measure that assesses the extent to which the skin condition has
affected the subject’s quality of life over the past week, including 6 domains (daily activities, 
personal relationships, symptoms and feelings, leisure, work/school, and treatment). The total 
score (0-30) is the sum of 10 questions with each ranging from 0 to 3. The scoring of each 
question (for Question 7 see below) is as follows:


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Response
Score
Very much
3
A lot
2
A little
1
Not at all
0
Not relevant
0
Question unanswered
0
Question 7: Over the last 
week, 
has 
your 
skin 
prevented 
you
from 
working or studying?
Question 7A: If “No”, over 
the last week how much has 
your skin been a problem at 
work or studying?
Score
Yes
Any response
3
No
A lot
2
No
A little
1
No
Not at all
0
Not relevant
Any response
0
If one question is left unanswered this is scored 0 and the scores are summed and expressed as 
usual out of a maximum of 30. If two or more questions are left unanswered the total DLQI score 
is missing. 
When summarizing the domain scores, if a domain contains two questions and the answer to one 
of the questions is missing, that domain will be scored as the answer to the non-missing question. 
If all the answers to questions in a domain are missing, the domain will not be scored.
DLQI total score and subscores on DLQI domains and their changes from baseline as well as
percent change from baseline values will be summarized descriptively. The following table 
identifies the DLQI domains and the questions that are summed in order to calculate them.
Domain
Questions
Symptoms and feelings
1 and 2
Daily activities
3 and 4
Leisure
5 and 6
Work and school
7
Personal relationships
8 and 9
Treatment
10


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11.10
Patient Satisfaction Questionnaire
.
11.11
Safety Analysis
All safety parameters will be summarized over the ITT population of all enrolled subjects,
overall and by DB treatment group.
11.11.1
Adverse Events
AE terms will be coded using Medical Dictionary for Regulatory Activities (MedDRA)
dictionary. All AEs reported in current study are considered as treatment-emergent AE (TEAE)
except for those AEs ongoing at the end of pivotal studies but resolved prior to the Visit 1 date in 
the extension study.
All TEAEs will be listed by subject, detailing the verbatim term given by the investigator, the 
preferred term (PT), system organ class (SOC), onset date and time, end date and time, ongoing 
at the end of pivotal studies (Y/N), duration (days), CTCAE grade, outcome, relationship to 
study drug, action taken with study drug, other action taken to treat the event, AE of special 
interest (Y/N), seriousness and criteria for seriousness.
AEs resolved prior to the Visit 1 date, Serious TEAEs (STEAEs), TEAEs leading to study 
discontinuation and TEAEs related to study drug will also be listed separately. The following 
adverse events of special interest (AESIs) will be identified and listed separately: contact
dermatitis, folliculitis, and headache.
The number and percent of subjects with TEAEs will be summarized as incidence rates of:
Any TEAE 
Any TEAE Excluding Those Ongoing at the end of the Pivotal Studies
Any TEAE Ongoing at the end of the Pivotal Studies
Any treatment-emergent AESIs 
Any treatment-emergent AESIs Excluding Those Ongoing at the end of the Pivotal 
Studies
Any treatment-emergent AESIs Ongoing at the end of the Pivotal Studies
Any treatment-related TEAE 
Any TEAE leading to study drug discontinuation
Any TEAE leading to study discontinuation
Any serious TEAE 


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Death
Treatment-related Serious TEAE
Serious TEAE leading to study drug discontinuation 
Serious TEAE leading to study discontinuation
TEAE (COVID-19)
Individual PTs will be summarized by SOC in alphabetical order and PT in descending order of 
frequency for the following subsets and subgroupings:
All TEAEs
All TEAEs by maximum CTCAE grade
All TEAEs by maximum causality (not related, related) to the study drug 
All TEAEs Excluding Those Ongoing at the End of the Pivotal Studies
All TEAEs ongoing at the end of the pivotal studies 
All treatment-related TEAEs
All TEAEs leading to study discontinuation
All TEAEs leading to study drug discontinuation 
All serious TEAEs
All TEAEs and all serious TEAEs will also be summarized by SOC (alphabetical order) and PT 
(descending order) for the following subgroups:
Age (<65 and >= 65 years old)
Sex 
Race (White, Other)
Furthermore, TEAEs will be categorized by day of onset among the following 4 categories:
12 weeks
>12 to 24 weeks
> 24 to 40 weeks
>40 weeks.
For each of these categories, TEAEs will be summarized by SOC in alphabetical order and PT in 
descending order of frequency. TEAEs ongoing at the end of the pivotal studies will be 
considered in the first category (i.e. day of onset 
12 weeks).
At each level of summarization, a subject will be counted once if he/she reported one or more 
events. The severity of TEAEs and relationship to study drug will be summarized in a similar 


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manner. For summaries of relationship to study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE CTCAE grade, a subject will be classified
according to the worst grade.
For AESIs, summarization will be more extensive, reflecting the more detailed information 
collected.  Information summarized will include number of events per subject, earliest onset day,
duration (in days), causality, grade and seriousness of AESIs, outcome, actions taken, assorted 
physical characteristics of the AESIs, and demographic/baseline characteristics and PGA status 
of the subjects experiencing them.  Each type of AESI will be summarized separately. If a
subject has more than one treatment-emergent occurrence of an AESI, the subject’s maximum
duration, highest levels of causality and seriousness, maximum grade and generally the most 
extreme level of each characteristic will be summarized. If an AESI was ongoing at end of study 
(EOS), it will not be included in the duration summary. AESIs ongoing at the end of pivotal 
studies will also be included in the summary.
A Kaplan-Meier figure will be generated for each AESI of time to first event for events starting 
during the study.  Subjects not experiencing the AESI will be censored at the date of study 
completion or discontinuation. AESIs ongoing at the end of pivotal studies will not be included.
11.11.2
Local Tolerability Scale (LTS)
LTS scores will be summarized by visit and DB treatment group for subject overall assessment
(scores from 0=None to 4=Strong/Severe) and Investigator overall assessment (scores from
0=No irritation to 4=Very Severe) separately. .LTS scores at the sensitive areas will be 
summarized by visit, area and DB treatment group for Investigator overall assessment as well as 
listed in a by-subject and by anatomical site listing.
11.11.3
Clinical Laboratory Testing
All clinical laboratory (hematology, clinical chemistry, urinalysis) values will be listed by DB 
treatment group and subject. The reference normal ranges and reference range indicators (e.g. 
high, low, normal etc.) will be supplied by the central laboratory and displayed in the data 
listings. For the purpose of shift table summaries, the central lab reported reference range 
indicators will be classified as low, normal and high accordingly based on the table below.
Reference Range Indicator in Shift Tables
Reference Range Indicator Reported by Central Lab
Low
Low, Low Level 1 Alert, Low Lever 2 Alert
Normal
Normal
High
High, High Level 1 Alert, High Level 2 Alert
Values outside the normal range will be flagged. Change from baseline in abnormality status will 
be summarized using shift tables. For urinalysis, only lab tests with numeric results reported are 
included in shift tables. Separate listings will identify subjects with markedly abnormal values.
For quantitative measures, observed values and change from baseline in clinical laboratory 
values will be summarized descriptively by visit, overall and by DB treatment group.




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According to the protocol, “Responses for each question of the Patient Satisfaction 
Questionnaire will be summarized by visit.” However, the PSQ was assessed only at the Week 
40 or at ET visits.  Consequently, it will be summarized overall rather than by visit.
Any additional statistical analyses to handle modifications to study conduct and/or missing data 
due to the COVID-19 pandemic have been documented in Section 11.12 above in this SAP and 
will be finalized prior to database lock.
13.HEADINGS
Each page of the analysis will show the sponsor’s name, the investigational product, and the 
protocol number. Report tables will be embedded in the MS Word report document from SAS 
program output without change. The footer of each table will show the name of the SAS program
module which generated it, the names of all data sets providing input data in the program and the 
date and time the table was generated.
14.ARCHIVING AND RETENTION OF DOCUMENTS
After finalization of the analysis, the following will be archived at IQVIA Biotech and/or with 
the study sponsor:
SAP and any amendments
All SAS code used in the project for statistical analysis, report tables generation, and 
analysis data set creation
Tables, listings and figures as included in the clinical study report
SAS study data tabulation model (SDTM) and analysis dataset model (ADaM) datasets
15.OUTLINE OF PROPOSED TABLES, LISTINGS AND FIGURES