Clinical trial NCT05680740
Conditions: Psoriasis
Keywords: Tapinarof Plaque psoriasis Adult Phase 4 Topical Open-label Efficacy Safety Psoriasis Intertriginous Psoriasis Inverse Psoriasis
Sponsor: Organon and Co
Start date: 2022-12-27; Completion date: 2023-05-25
Enrollment: 34 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is an open-label, multi-center study to evaluate the efficacy and safety of VTAMA (tapinarof) cream, 1% in adults with intertriginous psoriasis

Detailed description:
This is an open-label study in which participants will be assigned to receive VTAMA (tapinarof) cream, 1% once daily for 12 weeks. Study participants will have a follow-up period of 1 week. The study duration will be up to 17 weeks.

Arms: arm 1: VTAMA® (tapinarof) Cream 1% applied topically once daily
Interventions: intervention 1: VTAMA® (tapinarof) Cream 1%
Intervention descriptions: intervention 1: VTAMA® (tapinarof) Cream 1% applied topically once daily

Protocol documents:
Prot_002.pdf: 
DMVT-505 (tapinarof) 
IND 104601 
Dermavant Sciences, Inc. 
Clinical Study Protocol 
Confidential 
Page | 1 
 
 
Protocol Title:  
A Phase 4, open-label study to investigate the efficacy and safety of VTAMA® (tapinarof) cream, 1% in the 
treatment of plaque psoriasis in intertriginous areas 
Protocol Number:  DMVT-505-4001 
Product:  VTAMA (tapinarof) cream, 1% 
Brief Title:  
A study to investigate efficacy and safety of VTAMA® (tapinarof) cream, 1% in intertriginous plaque 
psoriasis  
Study Phase:  4 
Sponsor Name:  Dermavant Sciences, Inc. 
Legal Registered Address:  3300 Paramount Parkway, Suite 150, Morrisville, NC, USA  27560 
Regulatory Agency Identifier Number(s):  IND 104601 
 
 
 


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eSignature Approval 
 
14 Oct 2022 
 
 
Date Signed: 
This protocol has been approved by a representative of Dermavant Sciences, Inc.  This electronic signature is 
legally binding equivalent of traditional handwritten signatures and is captured in the audit trail of the 
document. 
 
Medical Monitoring 
Medical Monitor contact information can be found in the Study Reference Manual. 
Serious Adverse Event (SAE)/Pregnancy should be reported to the North American Safety Mailbox:  
 
 
Study Sponsor 
This study is sponsored by Dermavant Sciences, Inc. 
Sponsor Registered Address and Regulatory Contact 
Dermavant Sciences, Inc. 
3300 Paramount Parkway, Suite 150 
Morrisville, NC  27560 
USA 
 
 


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Table of Contents  
1 
Protocol Summary ........................................................................................................................ 8 
1.1 
Synopsis ........................................................................................................................................ 8 
1.2 
Schema .......................................................................................................................................... 12 
1.3 
Schedule of Activities ................................................................................................................... 13 
2 
Introduction ................................................................................................................................... 15 
2.1 
Study Rationale ............................................................................................................................. 15 
2.2 
Background ................................................................................................................................... 15 
2.3 
Benefit/Risk Assessment .............................................................................................................. 15 
2.3.1 
Risk Assessment ........................................................................................................................... 16 
2.3.2 
Benefit Assessment ....................................................................................................................... 16 
2.3.3 
Overall Benefit Risk Conclusion .................................................................................................. 16 
3 
Objectives and Endpoints ............................................................................................................. 17 
4 
Study Design ................................................................................................................................. 18 
4.1 
Overall Design .............................................................................................................................. 18 
4.2 
Scientific Rationale for Study Design .......................................................................................... 18 
4.3 
Justification for Dose .................................................................................................................... 18 
4.4 
End-of-Study Definition ............................................................................................................... 19 
5 
Study Population ........................................................................................................................... 20 
5.1 
Inclusion Criteria .......................................................................................................................... 20 
5.2 
Exclusion Criteria ......................................................................................................................... 20 
5.3 
Lifestyle Considerations ............................................................................................................... 23 
5.4 
Screen Failures .............................................................................................................................. 23 
5.5 
Criteria for Temporarily Delaying Enrollment ............................................................................. 23 
6 
Study Intervention(s) and Concomitant Therapy ......................................................................... 24 
6.1 
Study Intervention(s) Administered ............................................................................................. 24 
6.2 
Preparation, Handling, Storage, and Accountability .................................................................... 24 
6.3 
Assignment to Study Intervention ................................................................................................ 25 
6.4 
Blinding ........................................................................................................................................ 25 
6.5 
Study Intervention Compliance .................................................................................................... 25 
6.6 
Dose Modification ........................................................................................................................ 25 
6.7 
Continued Access to Study Intervention after the End of the Study ............................................ 25 
6.8 
Treatment of Overdose ................................................................................................................. 25 
6.9 
Prior and Concomitant Therapy .................................................................................................... 26 
7 
Discontinuation of Study Intervention and Participant Discontinuation/Withdrawal .................. 27 


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7.1 
Discontinuation of Study Intervention.......................................................................................... 27 
7.1.1 
Temporary Discontinuation .......................................................................................................... 27 
7.1.2 
Rechallenge ................................................................................................................................... 27 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................. 27 
7.3 
Lost to Follow up .......................................................................................................................... 27 
8 
Study Assessments and Procedures .............................................................................................. 29 
8.1 
Administrative and Baseline Procedures ...................................................................................... 29 
8.1.1 
Informed Consent ......................................................................................................................... 29 
8.1.2 
Demographics ............................................................................................................................... 29 
8.1.3 
Medical History ............................................................................................................................ 29 
8.1.4 
Instructions for Dosing Regimen .................................................................................................. 29 
8.2 
Efficacy Assessments ................................................................................................................... 30 
8.2.1 
Efficacy Assessments completed by Investigator ......................................................................... 30 
8.2.1.1 
Physician Global Assessment of Intertriginous Areas .................................................................. 30 
 
 
 
 
 
 
 
 
 
 
 
 
8.3 
Safety Assessments ....................................................................................................................... 31 
8.3.1 
Pregnancy Testing ........................................................................................................................ 31 
 
 
8.4 
Adverse Events,  Serious Adverse Events, and Other Safety Reporting ...................................... 32 
8.4.1 
Time Period and Frequency for Collecting AE and SAE Information ......................................... 32 
8.4.2 
Method of Detecting AEs and SAEs ............................................................................................ 32 
8.4.3 
Follow-up of AEs and SAEs ......................................................................................................... 32 
8.4.4 
Regulatory Reporting Requirements for SAEs ............................................................................. 33 
8.4.5 
Pregnancy ..................................................................................................................................... 33 
8.5 
Pharmacokinetics .......................................................................................................................... 33 
8.6 
Pharmacodynamics ....................................................................................................................... 33 
8.7 
Genetics ........................................................................................................................................ 33 
8.8 
Biomarkers .................................................................................................................................... 34 
8.9 
Immunogenicity Assessments ...................................................................................................... 34 
8.10 
Health Economics ......................................................................................................................... 34 


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9 
Statistical Considerations .............................................................................................................. 35 
9.1 
Statistical Hypothesis .................................................................................................................... 35 
9.1.1 
Multiplicity Adjustment................................................................................................................ 35 
9.2 
Analysis Sets ................................................................................................................................. 35 
9.3 
Statistical Analyses ....................................................................................................................... 35 
9.3.1 
General Considerations ................................................................................................................. 35 
9.3.2 
Primary Endpoint Analysis ........................................................................................................... 35 
9.3.3 
Secondary Endpoint Analysis ....................................................................................................... 35 
9.3.4 
Exploratory Endpoint(s) Analysis ................................................................................................ 35 
9.3.5 
Safety Analyses ............................................................................................................................ 36 
9.4 
Interim Analysis ............................................................................................................................ 36 
9.5 
Sample Size Determination .......................................................................................................... 36 
10 
Supporting Documentation and Operational Considerations ....................................................... 37 
10.1 
Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations ..................................... 37 
10.1.1 
Regulatory and Ethical Considerations ........................................................................................ 37 
10.1.2 
Financial Disclosure ..................................................................................................................... 37 
10.1.3 
Informed Consent Process ............................................................................................................ 37 
10.1.4 
Data Protection ............................................................................................................................. 38 
10.1.5 
Dissemination of Clinical Study Data .......................................................................................... 38 
10.1.6 
Data Quality Assurance ................................................................................................................ 38 
10.1.7 
Source Documents ........................................................................................................................ 39 
10.1.8 
Study and Site Start and Closure .................................................................................................. 39 
10.1.9 
Publication Policy ......................................................................................................................... 40 
10.2 
Appendix 2:  Clinical Laboratory Tests ........................................................................................ 41 
10.3 
Appendix 3:  AEs and SAEs:  Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ............................................................................................................. 42 
10.3.1 
Definition of AE ........................................................................................................................... 42 
10.3.2 
Definition of SAE ......................................................................................................................... 43 
10.3.3 
Recording and Follow-Up of AE and/or SAE .............................................................................. 44 
10.3.4 
Reporting of SAEs ........................................................................................................................ 45 
 
 
10.4 
Appendix 4:  Contraceptive and Barrier Guidance ....................................................................... 47 
10.4.1 
Definitions .................................................................................................................................... 47 
10.4.2 
Contraception Guidance ............................................................................................................... 49 
10.5 
Appendix 5:  Physician Global Assessment of Intertriginous Areas ............................................ 50 


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10.6 
 
10.7 
 
10.8 
 
10.9 
 
10.10 
 
11 
References ..................................................................................................................................... 57 
List of Tables 
Table 1: 
Study Intervention(s) Administered ............................................................................................. 24 
Table 2: 
Study Arm(s) ................................................................................................................................ 24 
Table 3: 
Fitzpatrick Skin Type Scale .......................................................................................................... 29 
Table 4: 
Criteria for Determining the Grade/Severity of Adverse Event Terms Not Specified by the 
National Cancer Institute CTCAE ................................................................................................ 44 
 
 
 


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List of Abbreviations  
Term 
Description 
AD 
atopic dermatitis 
AE 
adverse event 
AhR 
aryl hydrocarbon receptor 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CTCAE 
common terminology criteria for adverse events 
CV 
cardiovascular 
 
 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone 
GCP 
good clinical practice 
HRT 
hormonal replacement therapy 
IB 
Investigator’s brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
IND 
Investigational new drug application 
iPGA 
intertriginous Physician Global Assessment 
IRB 
institutional review board 
ITT 
intent-to-treat 
IU 
international units 
IUD 
intrauterine device 
 
 
 
 
OC 
observed cases 
PGA 
Physician Global Assessment 
 
 
PSO 
plaque psoriasis 
QD 
once a day 
SAE 
serious adverse event 
SoA 
schedule of activities 
SD 
standard deviation 
SUSARs 
suspected unexpected serious adverse reactions  
 
 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
USA 
United States of America 
USPI 
United States product insert 
UV 
ultraviolet 
WOCBP 
woman of childbearing potential 
WONCBP 
woman of nonchildbearing potential 


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1 Protocol Summary  
1.1 Synopsis  
Protocol Title:  A Phase 4, open-label study to investigate the efficacy and safety of VTAMA® (tapinarof) 
cream, 1% in the treatment of plaque psoriasis in intertriginous areas 
Brief Title:  A study to investigate efficacy and safety of VTAMA® (tapinarof) cream, 1% in intertriginous 
plaque psoriasis 
Regulatory Agency Identifier Number(s):  
IND 
104601 
Rationale:  
Among patients with PSO, up to 79% develop intertriginous PSO and 63% may develop genital PSO, 
although this may be underreported by patients due to embarrassment (Hong 2021).  Plaque PSO in these 
sensitive areas has a significant impact on patients’ quality of life (Khosravi 2017; Yang 2018).  
 
  
Intertriginous PSO, also called inverse PSO, is characterized by inflammatory lesions in skin folds including 
the axillae, perianal skin, antecubital fossae, popliteal fossae, intergluteal cleft, inframammary, 
genital/inguinal, abdominal, and retroauricular folds (Khosravi 2017).  Patients suffering from intertriginous 
PSO report negative body image, pain, fissuring, skin maceration, and embarrassment that impair daily 
activities, including clothing choice and personal hygiene (Khosravi 2017). 
The current first-line recommended therapy for plaque PSO in sensitive areas, including intertriginous areas 
and external genitalia, is low-potency topical corticosteroids (Khosravi 2017).  Increased systemic absorption, 
due to thin skin and the natural occlusion in these areas, exacerbates the known safety risks associated with 
topical corticosteroids and limits their use to short-term therapy.  Other topical therapies offer better safety 
profiles but with moderate efficacy.  Systemic treatment, such as biologics and oral therapy, is reserved for 
the more severe and resistant cases due to the more considerable adverse effects and cost associated with 
these agents associated with systemic treatment (Beck 2018).  There is a clear medical need for an effective 
topical treatment, without a safety profile that limits utility, for patients with plaque PSO in sensitive skin 
areas.  Dermavant has developed an effective, steroid-free, locally acting, cosmetically acceptable, elegant 
topical therapy that is safe and tolerable and offers patients the opportunity for a treatment-free remittive 
period.  Application of the product to plaque PSO in intertriginous areas was permitted in the Phase 3 
registrational trials to assess tolerability.  In addition, efficacy assessments in registrational trials included 
evaluation of plaques located in intertriginous regions as part of the overall response in treated areas.  
Although targeted efficacy responses were not evaluated in those specific areas, the USPI does not restrict 
application of VTAMA to intertriginous regions. 
VTAMA (tapinarof) cream, 1% was approved by the FDA in May 2022 for the treatment of plaque PSO in 
adults.  Tolerability in sensitive areas, including intertriginous areas, was excellent in Phase 3 pivotal studies 
and the long-term extension study for a total duration of up to 52 weeks (Lebwohl 2021; data on file).  This 
study will further assess efficacy and safety of VTAMA (tapinarof) cream, 1% when used to treat PSO in 
intertriginous areas. 
 
 




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Overall Design Synopsis:  
Brief Summary:  
The purpose of this open-label study is to evaluate the efficacy and safety of VTAMA (tapinarof) cream, 1% 
in adults with intertriginous PSO.  Efficacy of the treatment of plaque PSO in intertriginous areas will be 
assessed with a PGA evaluation only of intertriginous areas (iPGA).  
 
 Participants will be allowed 
to treat plaque PSO in other body areas according to instructions provided in USPI, but no assessments of 
efficacy will be performed outside of intertriginous 
 
VTAMA will be dispensed and will be administered at home between clinic visits as instructed by site 
personnel.  Application instructions will be reviewed at all clinic visits except during the final treatment/end-
of-study visits.  Participants will be instructed to apply cream QD to all affected areas, including intertriginous 
areas, and any other locations on the body.  Existing lesions will be treated as well as newly appearing lesions 
and lesions/areas that improved or cleared during the study.  Participants will apply sufficient cream to cover 
completely each lesion with a thin layer and will record the time of application in a daily diary provided by 
the study site.  Participants will be instructed to maintain the approximate dosing time chosen at the beginning 
of the study for their full study participation. 
Number of Participants:  
Approximately 30 participants will be enrolled. 
Note:  Enrolled means participants agreement to participate in a clinical study following completion of the 
informed consent process and screening.  Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in the study, are not considered enrolled, unless 
otherwise specified by the protocol.  A participant will be considered enrolled if the informed consent is not 
withdrawn prior to participating in any study activity after screening.   
Study Arms and Duration:  
VTAMA (tapinarof) cream, 1% is a white to off-white cream containing 1% weight/weight (10 mg/g) 
tapinarof, supplied in 60-gram tubes.  VTAMA is to be administered by the participant QD via topical 
application of a thin layer to affected areas in accordance with instructions in USPI. 
Dosing may be interrupted if deemed necessary by the Investigator for management of adverse events. 
Study duration: 
• The study duration will be up to 17 weeks. 
• The treatment duration will be up to 12 weeks. 
• The follow-up period will be up to 1 week. 
Statistical Methods 
Efficacy, safety, 
 will be summarized for the ITT 
population.   
Every effort will be made to collect complete data at all visits.  All efficacy data will be summarized based on 
OC.  The primary and exploratory efficacy endpoints will also be summarized utilizing the last observation 


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carried forward method to impute missing data 
 
 
Efficacy and Safety Analyses 
Demographics and baseline characteristics, efficacy, and all safety assessments 
 
, 
 will be summarized descriptively, no 
statistical comparisons will be performed.  Continuous data will be summarized by number of participants, 
mean, SD, median, minimum, and maximum, and categorical data will be summarized by frequency counts 
and percentages.  The 95% confidence intervals will be reported as appropriate.  Median time to event 
analyses will use the Kaplan-Meier product limit method (if estimable). 
Determination of Sample Size 
The sample size for this study is based on clinical considerations only.  No formal sample size calculation will 
be performed.  A total of 30 participants is planned for this study which is considered adequate to evaluate the 
efficacy and safety for the treatment of plaque psoriasis in the intertriginous areas. 
Data Monitoring/Other Committee: 
No data monitoring committee has been appointed for this study.








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2 Introduction  
VTAMA (tapinarof) cream, 1% was approved by the FDA in May 2022 for the treatment of plaque PSO in 
adults.  Tolerability in sensitive areas, including intertriginous areas, was excellent in Phase 3 pivotal studies 
and the long-term extension study for a total duration of up to 52 weeks (Lebwohl 2021; data on file).   
2.1 Study Rationale  
This study will further assess efficacy and safety of VTAMA (tapinarof) cream, 1% when used to treat PSO in 
intertriginous areas.   
2.2 Background  
Among patients with PSO, up to 79% develop intertriginous PSO and 63% may develop genital PSO, 
although this may be underreported by patients due to embarrassment (Hong 2021).  Plaque PSO in these 
sensitive areas has a significant impact on patients’ quality of life (Khosravi 2017; Yang 2018).  
 
.  
Intertriginous PSO, also called inverse PSO, is characterized by inflammatory lesions in skin folds including 
the axillae, perianal skin, antecubital fossae, popliteal fossae, intergluteal cleft, inframammary, 
genital/inguinal, abdominal, and retroauricular folds (Khosravi 2017).  Patients suffering from intertriginous 
PSO report negative body image, pain, fissuring, skin maceration, and embarrassment that impair daily 
activities, including clothing choice and personal hygiene (Khosravi 2017). 
The current first-line recommended therapy for plaque PSO in sensitive areas, including intertriginous areas 
and external genitalia, is low-potency topical corticosteroids (Khosravi 2017).  Increased systemic absorption, 
due to thin skin and the natural occlusion in these areas, exacerbates the known safety risks associated with 
topical corticosteroids and limits their use to only short-term therapy.  Other topical therapies offer better 
safety profiles but with moderate efficacy.  Biologics are reserved for the more severe and resistant cases due 
to the more severe adverse effects associated with systemic treatment (Beck 2018).  There is a clear medical 
need for an effective topical treatment, without a safety profile that limits utility, for patients with plaque PSO 
in sensitive skin areas. 
VTAMA (tapinarof) cream, 1% is a novel, cosmetically elegant, steroid-free topical cream that has 
demonstrated clinically meaningful and highly statistically significant efficacy in the treatment of plaque PSO 
and, thus, has the potential to meet the need in patients with plaque PSO in intertriginous areas.   
Application of the product to plaque PSO in intertriginous areas was permitted in the Phase 3 registrational 
trials to assess tolerability.  In addition, efficacy assessments in registrational trials included evaluation of 
plaques located in intertriginous regions as part of the overall response in treated areas.  Although targeted 
efficacy responses were not evaluated in those specific areas, the USPI does not restrict application of 
VTAMA to intertriginous regions.  A detailed description of the chemistry, pharmacology, efficacy, and 
safety of VTAMA (tapinarof) cream, 1% is provided in the IB. 
2.3 Benefit/Risk Assessment  
More detailed information about the known and expected benefits and risks and reasonably expected AEs of 
VTAMA (tapinarof) cream, 1% may be found in the IB. 


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2.3.1 Risk Assessment  
No major safety concerns were identified during the development program; no deaths or SAEs were 
considered related to VTAMA (tapinarof) cream, 1%.  Most AEs were mild localized skin reactions of a type 
commonly observed and managed by dermatologists.  A low incidence of safety issues, serious or 
non-serious, were observed.  The common AEs associated with the administration of VTAMA (tapinarof) 
cream, 1% in the clinical trials for plaque PSO were folliculitis, contact dermatitis, and headache.  Folliculitis 
events were generally mild and well tolerated and did not worsen or progress over time with continued 
treatment.  The vast majority of participants elected to continue with VTAMA (tapinarof) cream, 1% 
suggesting the perceived benefit outweighs the burden of folliculitis.  See Section 10.3.5 for further 
information on the management of follicular events.  Observations suggest that the events of contact 
dermatitis experienced by participants with plaque PSO may not represent allergic contact dermatitis.   
2.3.2 Benefit Assessment  
VTAMA (tapinarof) cream is a novel, cosmetically elegant, steroid-free topical cream that has demonstrated 
clinically meaningful and highly statistically significant efficacy in the treatment of plaque PSO consistently 
across the clinical program.  Benefits to participants include rapid improvement in signs and symptoms that 
persists with continued use, the ability to achieve complete disease clearance, and maintenance of disease 
control via a remittive effect after treatment discontinuation in a convenient once-daily topical therapy that 
can be administered for extended treatment durations with no limit to the size or location of the treatment 
area.  The remittive effect off therapy observed for VTAMA (tapinarof) cream, 1% is a unique and 
differentiating attribute that, coupled with durability on therapy, provides patients with a new option for 
long-term disease management.  These attributes are coupled with minimal systemic absorption and a 
favorable safety and tolerability profile. 
2.3.3 Overall Benefit Risk Conclusion  
Given the measures taken to minimize risk to participants participating in this study, the potential risks 
identified in association with VTAMA (tapinarof) cream are justified by the anticipated benefits that may be 
afforded to participants with plaque PSO in intertriginous areas.  Please see USPI for the most up-to-date 
information. 




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4 Study Design  
4.1 Overall Design  
This is a single-group, open-label, multicenter study to evaluate the safety and efficacy of VTAMA 
(tapinarof) cream, 1% in the treatment of plaque PSO in intertriginous areas.  Participants will treat plaque 
PSO in intertriginous areas with VTAMA (tapinarof) cream, 1% QD for 12 weeks.  Efficacy of the treatment 
of plaque PSO in intertriginous areas will be assessed with a PGA evaluation only of intertriginous areas 
(iPGA).  In
 
 Participants will be allowed to treat plaque PSO in other body 
areas according to instructions provided in USPI, but no assessments of efficacy will be performed outside of 
intertriginous 
 
Study duration: 
• The study duration will be up to 17 weeks. 
• The treatment duration will be up to 12 weeks. 
• The follow-up period will be up to 1 week. 
4.2 Scientific Rationale for Study Design  
The safety and efficacy of VTAMA (tapinarof) cream, 1% in the treatment of plaque PSO were established in 
Phase 3 studies, which included the treatment of sensitive areas.  This study is intended to broaden the 
understanding of the safety and efficacy of VTAMA (tapinarof) cream, 1% in the treatment of plaque PSO 
occurring in intertriginous areas.  Efficacy and tolerability in these areas, 
 
.   
The PGA is a clinical tool for assessing the current state/severity of a participant’s PSO at a given time point.  
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.  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.  
Improvements in PGA generally correlate with improvements in quality of life.  The primary endpoint will 
assess the percentage of participants who achieve an iPGA score of clear (0) or almost clear (1) with a ≥ 2-
grade improvement from Baseline at Week 12.  The type of endpoint is well established as means of 
measuring the success of treatments in plaque PSO.  The secondary endpoint will assess the time to achieve 
an iPGA score of 0 or 1, as onset of action is incredibly important to patients in the clinic. 
 
 
  
 
 
 
4.3 Justification for Dose  
The FDA-approved dosing regimen for VTAMA (tapinarof) cream, 1% for the treatment of plaque PSO is 
QD dosing and will be followed in this study.  This regimen is based on the evaluation of various tapinarof 


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regimens in participants with plaque PSO and AD and the success of this regimen in Phase 3 studies in 
participants with plaque PSO.   
4.4 End-of-Study Definition  
The end of the study is defined as the date of the last visit of the last participant in the study.   
 


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5 Study Population  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol 
waivers or exemptions, is not permitted. 
5.1 Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 years of age or older, at the time of signing the informed consent. 
Type of Participant and Disease Characteristics 
2. Participants with clinical diagnosis of plaque PSO, including lesion(s) in intertriginous area(s) and 
stable disease in intertriginous areas for at least 3 months prior to the study 
3. An iPGA score of 2 (mild), 3 (moderate), or 4 (severe) at screening and baseline.   
Sex and Contraceptive/Barrier Requirements 
Contraceptive use by men and women should be consistent with local regulations regarding the methods of 
contraception for those participating in clinical studies. 
4. Female participants: 
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the 
following conditions applies: 
• Is a WONCBP as defined in Appendix 4 Contraceptive and Barrier Guidance  
OR 
• Is a WOCBP and using an acceptable contraceptive method as described in Appendix 4 
Contraceptive and Barrier Guidance during the treatment period, until after the last dose of study 
product.  The Investigator should evaluate the potential for contraceptive method failure (e.g., 
noncompliance, recently initiated) in relationship to the first dose of study product). 
o A WOCBP must have a negative urine pregnancy test before the first dose of study product, 
see Section 8.3.1 Pregnancy Testing.   
o The Investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
Informed Consent 
5. Capable of giving signed informed consent as described in Appendix 1 which includes compliance 
with the requirements and restrictions listed in the ICF and in this protocol; written informed consent 
must be obtained prior to any study related procedures. 
5.2 Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Diagnosis of a type of psoriasis other than plaque PSO 


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2. Any sign of infection of any of the psoriatic lesions 
3. Concurrent significant dermatologic or inflammatory condition other than plaque PSO that, in the 
Investigator’s opinion, would make it difficult to interpret data or assessments during the study 
4. A history of or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the 
Investigator’s opinion, may interfere with participation in the study and ability to understand and give 
informed consent. 
5. History of sensitivity to the study product, or components thereof or a history of drug or other allergy 
that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study. 
Prior/Concomitant Therapy 
6. Previous OR current use of VTAMA. 
7. Use of any prohibited medication within the indicated period before the Baseline visit. 
NOTE:  Prohibited concomitant medications, therapy, etc., during the defined period are as listed in the 
bullets below.  If a participant requires any of these medications throughout the study period, he/she may 
be excluded from or discontinued from the study. 
• Minimum of 5 half-lives for biologic agents: e.g., 12 months for rituximab; 8 months for 
ustekinumab; 5 months for secukinumab, risankizumab or tildrakizumab; 12 weeks for golimumab 
or guselkumab; 10 weeks for ixekizumab or infliximab; 8 weeks for infliximab, adalimumab, 
alefacept, or brodalumab; and 4 weeks for etanercept 
• Four weeks for systemic treatments: deucravacitinib, 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), psolarens, corticosteroids, or 
adrenocorticotropic hormone analogs 
• Two weeks for immunizations with a live viral component; drugs known to possibly worsen PSO, 
such as beta-blockers (e.g., propranolol), lithium, iodides, angiotensin-converting enzyme 
inhibitors, and indomethacin, unless on a stable dose for > 12 weeks 
• With the exception of non-medicated emollients, 2 weeks for topical treatments including 
corticosteroids, roflumilast, antihistamines, immunomodulators, anthralin (dithranol), vitamin D 
derivatives (e.g., calcipotriene, calcipotriol), retinoids (Note:  4 weeks for tazarotene), or coal tar 
• NOTE:  If participants are on a stable regimen of non-medicated emollient(s), they may continue 
to use the same emollient(s) on nonlesional skin during the study.   
Prior/Concurrent Clinical Study Experience 
8. Current enrollment OR past participation in another investigational study in which tapinarof was 
administered.  
9. The participant has received an investigational product within the following time period prior to the 
first dosing day in the current study:  30 days, 5 half-lives, or twice the duration of the biological 
effect of the study product (whichever is longer). 
Other Exclusion Criteria 
10. UV light therapy or prolonged exposure to natural or artificial sources of UV radiation (e.g., 
phototherapy, tanning beds/booths, or therapeutic sunbathing) within 4 weeks prior to the Baseline 


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visit and/or plans to have such exposures during the study which could potentially impact the 
participant's PSO (as determined by the Investigator). 


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5.3 Lifestyle Considerations  
Timing of Study Product Application 
• Participants will be instructed to maintain the approximate dosing time chosen at the beginning of 
the study for their full study participation. 
• Participants should avoid swimming, bathing, showering, or strenuous activities for at least 2 hours 
after application. 
• If the participant elects to apply study product in the evening, the dose should be applied at least 
30 minutes prior to bedtime. 
5.4 Screen Failures  
A screen failure occurs when a participant who has consented to participate in the clinical study is not 
subsequently entered in the study.  A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the CONSORT publishing requirements and to 
respond to queries from regulatory authorities.  Minimal information includes demography, screen failure 
details, eligibility criteria, and any AEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be rescreened 
1 time.  Rescreened participants should be assigned a new participant number. 
5.5 Criteria for Temporarily Delaying Enrollment 
Not applicable 


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6 Study Intervention(s) and Concomitant Therapy  
Study products are all prespecified, investigational and non-investigational medicinal products, medical 
devices, and other interventions (e.g., surgical and behavioral) intended to be administered to the study 
participants during the study conduct. 
6.1 Study Intervention(s) Administered  
Table 1: 
Study Intervention(s) Administered  
Intervention 
Name 
VTAMA (tapinarof) cream, 1% 
Intervention 
Description 
A thin layer of cream (tapinarof 1%) applied to lesions QD  
Type  
Drug 
Dose 
Formulation 
Cream 
Unit Dose 
Strength(s) 
cream, 1% 
Dosage 
Level(s) 
Total dosage is dependent on BSA affected 
Route of 
Administration 
Topical 
Use 
Experimental 
IMP and 
NIMP/AxMP 
IMP  
Sourcing 
Provided centrally by the Sponsor to study site for distribution 
Packaging and 
Labeling 
VTAMA (tapinarof) cream, 1% will be provided in 60-g commercial tubes and labeled to be distributed in the 
participating country and will meet all applicable requirements. 
Current/ 
Former 
Names/Aliases 
DMVT-505, formerly known as GSK2894512A, GSK2894512, STI-1001, WBI-1001, or JTE-061 
AxMP = auxiliary medical product; BSA = body surface area; GSK = GlaxoSmithKline; IMP = Investigational Medicinal Product; 
NIMP = non-investigational medical product; QD = once daily. 
Table 2: 
Study Arm(s)  
Arm Title 
VTAMA (tapinarof) cream, 1% 
Arm Type 
Experimental: open-label 
Arm 
Description 
Participants will apply sufficient study product to completely cover each lesion with a thin layer QD for 
12 weeks.  Participants will treat all lesions in intertriginous areas 
 
  Participants may treat plaque PSO in other areas; however, improvement of PSO in these areas will 
not be included in any efficacy analyses. 
Participants will be instructed to maintain the same approximate dosing time chosen at the beginning of the 
study for their full study participation. 
PSO = psoriasis; QD = once daily 
6.2 Preparation, Handling, Storage, and Accountability  
11. The Investigator or designee must confirm appropriate conditions (e.g., temperature) have been 
maintained during transit for all study product received, and any discrepancies are reported and 
resolved before use of the study product. 
12. Only participants enrolled in the study may receive study product, and only authorized site staff may 
supply study product.   


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13. All study product must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to the 
Investigator and authorized site staff. 
14. The Investigator or authorized site staff is responsible for study product accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records). 
15. Further guidance and information for the final disposition of unused study products are provided in the 
Study Reference Manual. 
6.3 Assignment to Study Intervention  
Not applicable 
6.4 Blinding  
This is an open-label study. 
6.5 Study Intervention Compliance  
At Visit 2, study product will be dispensed, and participants will be instructed on how to apply cream and will 
apply the study product application under supervision.  During the study, participants will self-administer 
study product(s) at home and will record the time of study product application in a daily diary provided by the 
study site.  Participants will be instructed to maintain the same approximate dosing time chosen at the 
beginning of the study for their full study participation.  Compliance with study product will be assessed at 
each visit based on diary entries.  Participants will be instructed to bring all used and unused tubes with them 
to each study visit.  If a tube has been lost, discarded, or forgotten by the participant, then the site personnel 
will make a notation of this on the drug accountability logs.  Forgotten tubes should be returned by the 
participant at the next study visit.  Unopened tubes and opened, partially used tubes or tubes with foil overlay 
removed may only be re-dispensed once to study participants.  A new tube may be dispensed if the current 
tube does not contain sufficient study product to last until the next visit.  All tubes, including empty tubes, 
will be collected at Visit 8.  Deviation(s) from the prescribed dosage regimen should be recorded. 
A record of the quantity of study product dispensed to and administered by each participant must be 
maintained and reconciled with study product and compliance records.  Intervention start and stop dates, 
including dates for intervention delays, will also be recorded. 
6.6 Dose Modification  
Dosing may be interrupted if deemed necessary by the Investigator for management of AEs. 
6.7 Continued Access to Study Intervention after the End of the Study  
VTAMA (tapinarof) cream, 1% is commercially available for the treatment of plaque PSO. 
6.8 Treatment of Overdose  
For this study, accidental or intentional oral ingestion of drug product will be considered an overdose.  
Ingestion of a 60-gram tube of VTAMA (tapinarof) cream, 1% would result in an oral dose of 600 mg of 
tapinarof. 


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The Sponsor does not recommend specific treatment for an overdose; however, in the event of an overdose, 
the Investigator (or treating physician) should do the following: 
• Contact Medical Monitor to discuss the event 
• Closely monitor the participant for AEs/SAEs and laboratory abnormalities 
• Provide general symptomatic treatment as necessary 
• Document the quantity of the excess dose as well as the duration of the overdosing 
Decisions regarding dose interruptions or modifications following an overdose will be made by the 
Investigator in consultation with the Medical Monitor based on the clinical evaluation of the participant. 
6.9 Prior and Concomitant Therapy  
Any medication or vaccine, including over the counter or prescription medicines, recreational drugs, vitamins, 
and/or herbal supplements, as well as non-medicated emollients, that the participant is utilizing at the time of 
consent or receives during the study must be recorded along with: 
• Reason for use  
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The medical monitor should be contacted if there are any questions regarding concomitant or prior therapy. 
Concomitant medications for medical treatment of other conditions are allowed, under the condition that the 
dosage and administration of these treatments are 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 5.2.   
In the event of skin infection, topical antibacterial agents can be applied to the infected area; however, study 
product must not be applied to the area until the skin infection is healed. 
Participants may use non-medicated shampoos (must not contain corticosteroids, vitamin D analogs, salicylic 
acid, or coal tar).  Non-medicated emollients may be used outside of the intertriginous areas; emollients 
should not be applied to intertriginous skin.  The same emollient should be used throughout participation in 
the study.   


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7 Discontinuation of Study Intervention and Participant Discontinuation/Withdrawal  
Discontinuation of specific sites or of the study as a whole are detailed in Appendix 1. 
7.1 Discontinuation of Study Intervention  
In rare instances, it may be necessary for a participant to permanently discontinue study product.  If study 
product is permanently discontinued, the participant should, if at all possible, remain in the study to be 
evaluated for safety.  See the SoA for data to be collected at the time of discontinuation of study product and 
follow-up and for any further evaluations that need to be completed. 
7.1.1 Temporary Discontinuation  
Some dermatological reactions have been observed following treatment with VTAMA (tapinarof) cream, 1% 
(see Section 2.3.1).  After cessation of exposure, dermatological reactions generally subside spontaneously or 
with topical treatments. 
In this study, treatment of plaque PSO in intertriginous regions with study product may be interrupted for 
dermatological reactions.  If treatment is interrupted due to a safety issue, the Medical Monitor will be 
contacted, and the event documented in the eCRF. 
See Section 10.3.5 for further information on the management of follicular events. 
7.1.2 Rechallenge  
If study product is temporarily discontinued due to dermatological reactions, treatment may be resumed at the 
Investigator’s discretion when the reaction has subsided. 
7.2 Participant Discontinuation/Withdrawal from the Study  
• A participant may withdraw from the study at any time at the participant’s own request for any 
reason (or without providing any reason). 
• A participant may be withdrawn at any time at the discretion of the Investigator for safety or 
compliance reasons.   
• At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA.  See SoA for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
• The participant will be permanently discontinued from the study product and the study at that time. 
• If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
• If a participant withdraws from the study, the participant may request destruction of any samples 
taken and not tested, and the Investigator must document this in the site study records. 
7.3 Lost to Follow up  
A participant will be considered lost to follow-up if the participant 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 participant fails to return to the clinic for a required study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as possible, 
counsel the participant on the importance of maintaining the assigned visit schedule, and ascertain 
whether the participant wishes to and/or should continue in the study. 


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• Before a participant is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the participant (where possible, 3 telephone calls, and if necessary, a 
certified letter to the participant’s last known mailing address or local equivalent methods).  These 
contact attempts should be documented in the participant’s medical record. 
• Should the participant continue to be unreachable, the participant will be considered to have 
withdrawn from the study.   
 


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8 Study Assessments and Procedures  
• Study procedures and their timing are summarized in the SoA.  Protocol waivers or exemptions are 
not allowed. 
• Adherence to the study design requirements, including those specified in the SoA, is essential and 
required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria.  The Investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
• In the event of a significant study-continuity issue (e.g., caused by a pandemic), alternate strategies 
for participant visits, assessments, medication distribution, and monitoring may be implemented by 
the Sponsor or the Investigator, as per local health authority/ethics requirements.   
8.1 Administrative and Baseline Procedures  
8.1.1 Informed Consent  
The Investigator is responsible for obtaining written informed consent 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 informed consent.  Each informed consent will be appropriately signed 
and dated by the participant and the person obtaining consent. 
8.1.2 Demographics  
Demographic information collected will include age, sex, race, ethnicity, and Fitzpatrick skin type (Table 3).   
Table 3: 
Fitzpatrick Skin Type Scale  
Skin Type 
Sunburn Tendency 
Suntan Tendency  
Type I 
Always burns easily 
Never tan 
Type II 
Always burns easily 
Tans slightly 
Type III 
Burns moderately 
Tans gradually 
Type IV 
Burns minimally 
Tans moderately 
Type V 
Rarely burns 
Tans profusely 
Type VI 
Never burns 
Tans profusely 
8.1.3 Medical History  
Medical history will be collected to ensure participants are eligible for participation in the study (per inclusion 
Section 5.1 and exclusion Section 5.2 criteria).   
Data collected will include year of plaque PSO diagnosis, allergic conditions, and CV medical history and risk 
factors (medical conditions, and family history of premature CV disease).   
If a participant has previously tested positive for COVID-19 or has previously received a COVID-19 vaccine, 
it should be documented in the participant’s medical history. 
8.1.4 Instructions for Dosing Regimen  
Participants will self-administer study product at home, QD, and will record the time of application in a daily 
diary provided by the study site.   


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Application Instructions 
Participants will be instructed to: 
• Treat all lesions in intertriginous areas, both newly appearing lesions and lesions that have 
improved or cleared during the study 
Note:  Participants may treat plaque PSO in other areas according to instructions provided in the 
USPI.  No other treatment for scalp PSO is permitted during the study. 
• Apply cream to dry, clean skin in an amount sufficient to completely cover each lesion with a thin 
layer 
• Continue to lightly rub any residual cream visible on the disease-affected skin until it is no longer 
visible 
• Wash hands after application, unless treating lesions on the hands or fingernails 
Timing of Application 
Participants will be instructed to: 
• Maintain the approximate time of day for dosing at home throughout their full study participation 
• Record the time of application in the daily diary 
• Apply cream at least 30 minutes prior to bedtime if their chosen application time is in the evening 
• Avoid swimming, bathing, showering, or strenuous activities for at least 2 hours after application  
Missed Doses 
A missed daily dose will be recorded as a protocol deviation.   
Participants will be instructed that if a dose is missed, they should continue dosing the next day and should 
not apply more than QD to make up for the missed dose on the previous day. 
8.2 Efficacy Assessments   
Planned time points for all efficacy assessments are provided in the SoA. 
8.2.1 Efficacy Assessments completed by Investigator  
To minimize inter-observer 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 site.  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. 
8.2.1.1 
Physician Global Assessment of Intertriginous Areas  
The PGA is a clinical tool for assessing the current state/severity of a participant’s PSO at a given time point.  
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 (see Appendix 5).   
In this study, the PGA should be used only to assess plaque PSO in intertriginous areas (iPGA). 


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8.2.1.2 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
   
 
   
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
  
 
   
8.3 Safety Assessments  
Planned time points for all safety assessments are provided in the SoA. 
8.3.1 Pregnancy Testing  
• Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
• Refer to the SoA for timing of periodic scheduled urine pregnancy tests. 




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stabilization, the event is otherwise explained, or the participant is lost to follow-up (as defined in 
Section 7.3).  Further information on follow-up procedures is provided in Appendix 3. 
8.4.4 Regulatory Reporting Requirements for SAEs  
• Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
product under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study product under clinical investigation.  The Sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRBs/IECs, and Investigators. 
• An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review, acknowledge 
electronically, and retain a copy within the Study Reference Manual and will notify the IRB/IEC, 
if appropriate according to local requirements. 
• Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to Investigators as necessary. 
8.4.5 Pregnancy  
• Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study product and until the last dose of study 
product. 
• If a pregnancy is reported, the Investigator will record pregnancy information on the appropriate 
form and submit it to the Sponsor within 24 hours of learning of the female participant or female 
partner of a male participant (after obtaining the necessary signed informed consent from the 
female partner) pregnancy. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
• The participant/pregnant female partner will be followed to determine the outcome of the 
pregnancy.  The Investigator will collect follow-up information on the participant/pregnant female 
partner and the neonate, and the information will be forwarded to the Sponsor. 
• Any poststudy pregnancy-related SAE considered reasonably related to the study product by the 
Investigator will be reported to the Sponsor as described in Section 8.4.4.  While the Investigator is 
not obligated to actively seek this information in former study participants/pregnant female 
partner, he or he may learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will discontinue 
study product or be withdrawn from the study. 
8.5 Pharmacokinetics  
Pharmacokinetic parameters are not evaluated in this study. 
8.6 Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
8.7 Genetics  
Genetics are not evaluated in this study. 


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8.8 Biomarkers  
Biomarkers are not evaluated in this study. 
8.9 Immunogenicity Assessments  
Immunogenicity is not evaluated in this study. 
8.10 Health Economics   
Health economics parameters are not evaluated in this study. 
 




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9.3.5  Safety Analyses   
 
   
The number and percent of participants with TEAEs will be summarized by system organ class, and preferred 
term for all TEAEs, all TEAEs by system organ class, preferred term, and maximum CTCAE grade, all 
TEAEs considered by the Investigator to be related to study product, SAEs, TEAEs leading to study product 
discontinuation, and TEAEs leading to discontinuation from study. 
9.4 Interim Analysis  
Not applicable 
9.5 Sample Size Determination  
The sample size for this study is based on clinical considerations only.  No formal sample size calculation will 
be performed.  A total of 30 participants is planned for this study which is considered adequate to evaluate the 
efficacy and safety for the treatment of plaque PSO in the intertriginous areas. 


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10 Supporting Documentation and Operational Considerations  
10.1 Appendix 1:  Regulatory, Ethical, and Study Oversight Considerations  
10.1.1 Regulatory and Ethical Considerations  
• This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the Declaration of 
Helsinki and Council for International Organizations of Medical Sciences international ethical 
guidelines 
o Applicable ICH GCP guidelines 
o Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator’s brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to study 
participants.   
• Protocols and any substantial amendments to the protocol will require health authority approval 
prior to initiation (if applicable per country- or region-specific regulations) except for changes 
necessary to eliminate an immediate hazard to study participants. 
• The Investigator will be responsible for the following, as applicable: 
o Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures 
o Providing oversight of the conduct of the study at the site and adherence to requirements of 
21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies, 
European Medical Device Regulation 2017/745 for clinical device research, and all other 
applicable local regulations 
10.1.2 Financial Disclosure  
Investigators and Sub-Investigators will provide the Sponsor with sufficient, accurate financial information as 
requested to allow the Sponsor to submit complete and accurate financial certification or disclosure statements 
to the appropriate regulatory authorities.  Investigators and Sub-Investigators are responsible for providing 
information on financial interests during the course of the study and for 1 year after completion of the study. 
10.1.3 Informed Consent Process  
• The Investigator or the Investigator’s representative will explain the nature of the study, including 
the risks and benefits, to the potential and answer all questions regarding the study. 
• Potential participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, privacy and data protection requirements, where applicable, and the 
IRB/IEC or study center. 
• The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained.  The 
authorized person obtaining the informed consent must also sign the ICF. 


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• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
10.1.4 Data Protection  
• Participants will be assigned a unique identifier by the Sponsor.  Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred. 
• The participant must be informed that their personal study-related data will be used by the Sponsor 
in accordance with local data protection law.  The level of disclosure must also be explained to the 
participant who will be required to give consent for their data to be used as described in the 
informed consent  
• The participant must be informed that their medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
• The contract between Sponsor and study sites specifies responsibilities of the parties related data 
protection, including handling of data security breaches and respective communication and 
cooperation of the parties. 
• Information technology systems used to collect, process, and store study-related data are secured 
by technical and organizational security measures designed to protect such data against accidental 
or unlawful loss, alteration, or unauthorized disclosure or access. 
10.1.5 Dissemination of Clinical Study Data  
Anonymized Clinical Study Reports will be disclosed as required by regulatory authorities. 
Study information and tabular study results will be posted on National Institutes of Health’s website 
www.clinicaltrials.gov and other publicly accessible sites.  Study results may be published in peer-reviewed 
publications or presented at scientific meetings. 
Following an assessment of a rigorously defined research question from a third party, Dermavant may grant 
access to analyzable datasets from this study through a secure system.   
10.1.6 Data Quality Assurance  
• All participant data relating to the study will be recorded on printed or electronic CRFs unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data).  The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF. 
• Guidance on completion of CRFs will be provided in CRF completion guidelines. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source documents. 
• Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the Study Reference Manual. 
• The Sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. 


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• The Sponsor assumes accountability for actions delegated to other individuals (e.g., contract 
research organizations). 
• Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period.  No records may be destroyed during the 
retention period without the written approval of the Sponsor.  No records may be transferred to 
another location or party without written notification to the Sponsor. 
10.1.7 Source Documents  
• Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected.  Source documents are filed at the Investigator’s site. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source documents must 
be consistent with the source documents or the discrepancies must be explained.  The Investigator 
may need to request previous medical records or transfer records, depending on the study.  Also, 
current medical records must be available. 
• Definition of what constitutes source data and its origin can be found in source data 
acknowledgment. 
• The Investigator must maintain accurate documentation (source data) that supports the information 
entered in the eCRF. 
• The Sponsor or designee will perform monitoring to confirm that data entered into the CRF by 
authorized site personnel are accurate, complete, and verifiable from source documents; that the 
safety and rights of participants are being protected; and that the study is being conducted in 
accordance with the currently approved protocol and any other study agreements, ICH GCP, and 
all applicable regulatory requirements. 
10.1.8 Study and Site Start and Closure  
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of participants. 
The first act of recruitment is the first site activated and will be the study start date. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor.  Study sites will be closed upon study completion.  A study site is 
considered closed when all required documents and study supplies have been collected and a study-site 
closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause and sufficient 
notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are not limited to: 
For study termination: 
• Discontinuation of further study product development 
For site termination: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or local 
health authorities, the Sponsor’s procedures, or GCP guidelines 


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• Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants by the 
Investigator 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the Investigators, the 
IECs/IRBs, the regulatory authorities, and any contract research organization(s) used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements.  The Investigator 
shall promptly inform the participant and should assure appropriate participant therapy and/or follow-up. 
10.1.9 Publication Policy  
• The results of this study may be published or presented at scientific meetings.  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, Inc. request to delete references to its 
confidential information (other than the study results) in any paper or presentation and agrees to 
withhold publication or presentation for an additional 60 days in order to obtain patent protection 
if deemed necessary.  This allows the Sponsor to protect proprietary information and to provide 
comments. 
• After conclusion of the study and without prior written approval from Dermavant Sciences, Inc., 
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: 
− The results of the study in their entirety have been publicly disclosed by or with the consent of 
Dermavant Sciences, Inc., in an abstract, manuscript, or presentation form; OR 
− The study has been completed at all study sites for at least 5 years. 
• No such communication, presentation, or publication will include Dermavant Sciences, Inc. 
confidential information. 
• The Sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data.  In this case, a coordinating 
Investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
 


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10.2 Appendix 2:  Clinical Laboratory Tests  
No clinical laboratory tests will be performed in this study. 
 
 


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10.3 Appendix 3:  AEs and SAEs:  Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting  
10.3.1 Definition of AE  
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, temporally associated 
with the use of study product, whether or not considered related to the study product. 
• NOTE:  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 study product. 
Definition of Unsolicited and Solicited AE 
• An unsolicited AE is an AE that was not solicited using a participant diary and that is 
communicated by a participant who has signed the informed consent.  Unsolicited AEs include 
serious and nonserious AEs. 
• Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses requiring a 
hospitalization, emergency room visit, or visit to/by a healthcare provider).  The participant will be 
instructed to contact the site as soon as possible to report medically attended event(s), as well as 
any events that, though not medically attended, are of participant concern.  Detailed information 
about reported unsolicited AEs will be collected by qualified site personnel and documented in the 
participant’s records. 
• Unsolicited AEs that are not medically attended nor perceived as a concern by the participant will 
be collected during an interview with the participant and by review of available medical records at 
the next visit. 
• Solicited AEs are predefined local and systemic events for which the participant is specifically 
questioned, and which are noted by the participant in their diary. 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (i.e., not related to progression of underlying disease, or more severe than expected for 
the participant’s condition) 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition 
• New condition detected or diagnosed after study product administration even though it may have 
been present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study product or a 
concomitant medication.  Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent.  Such overdoses should be 
reported regardless of sequelae. 
• 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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Events not Meeting the AE Definition 
• Any abnormal laboratory findings or other abnormal safety assessments that are associated with 
the underlying disease, unless judged by the Investigator to be more severe than expected for the 
participant’s condition 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition 
• Medical or surgical procedure (e.g., endoscopy, appendectomy):  The condition that leads to the 
procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital) 
• 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 
10.3.2 Definition of SAE  
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria 
listed: 
a. Results in death 
b. Is life threatening 
The term life threatening in the definition of serious refers to an event in which the participant was at risk of 
death at the time of the event.  It does not refer to an event, which hypothetically might have caused death, if 
it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the participant has been admitted (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 outpatient 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. 
d. Results in persistent or significant disability/incapacity 
• The term disability means 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, influenza, and accidental trauma (e.g., 
sprained ankle) that may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Is a suspected transmission of any infectious agent via an authorized medicinal product 
g. Other situations: 
• Medical or scientific judgment should be exercised by the Investigator in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the participant 


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or may require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition.  These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, convulsions not 
resulting in hospitalization, or development of intervention dependency or intervention abuse. 
10.3.3 Recording and Follow-Up of AE and/or SAE  
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• The Investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the Investigator to send photocopies of the participant’s medical records to 
the Sponsor in lieu of completion of the required form. 
• There may be instances when copies of medical records for certain cases are requested by 
regulatory authorities.  In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to regulatory 
authorities. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information.  Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
• 
 
Assessment of Severity 
The Investigator will make an assessment of severity for each AE and SAE reported during the study 
according to the National Cancer Institute 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. 
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 
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. 
CTCAE = Common Terminology Criteria for Adverse Events. 


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Assessment of Causality 
• The Investigator is obligated to assess the relationship between study product and each occurrence 
of each AE/SAE.  The Investigator will use clinical judgment to determine the relationship. 
• A reasonable possibility of a relationship conveys that there are facts, evidence, and/or arguments 
to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study product administration, will be considered 
and investigated. 
• For causality assessment, the Investigator will also consult the IB and/or product information, for 
marketed products. 
• The Investigator must review and provide an assessment of causality for each AE/SAE and 
document this in the medical notes.  There may be situations in which an SAE has occurred, and 
the Investigator has minimal information to include in the initial report to the Sponsor or designee.  
However, it is very important that the Investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to the Sponsor or designee. 
• The Investigator may change their opinion of causality in light of follow-up information and send 
an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the Sponsor or designee to elucidate 
the nature and/or causality of the AE or SAE as fully as possible.  This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other health 
care professionals. 
• If a participant dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide the Sponsor with a copy of any postmortem findings including 
histopathology, if applicable. 
• New or updated information will be recorded in the originally submitted documents. 
• The Investigator will submit any updated SAE data to the Sponsor or designee within 24 hours of 
receipt of the information. 
10.3.4 Reporting of SAEs  
SAE Reporting to Sponsor via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the Sponsor or designee will be the electronic 
data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data collection tool (see 
next section) to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes available. 
• After the study is completed at a given site, the electronic data collection tool will be taken offline 
to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken offline, then the 


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site can report this information on a paper SAE form (see next section) or to the Sponsor or 
designee by telephone. 
• Contacts for SAE reporting can be found in Study Reference Manual. 
SAE Reporting to Sponsor or Designee via Paper Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred method to transmit 
this information to the Sponsor or designee or the SAE coordinator. 
• Initial notification via telephone does not replace the need for the Investigator to complete and sign 
the SAE data collection tool within the designated reporting timeframes. 
• Contacts for SAE reporting can be found in the Study Reference Manual. 
  
 
 
 
 
 
 
 
   
 
 
 


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10.4 Appendix 4:  Contraceptive and Barrier Guidance  
10.4.1 Definitions  
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming postmenopausal unless permanently sterile (see below) 
• A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. 
o A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state 
in women not using hormonal contraception or HRT.  However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required.   
o Females on HRT and whose menopausal status is in doubt will be required to use one of the 
nonestrogen hormonal highly effective contraception methods if they wish to continue their 
HRT during the study.  Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
o For individuals with permanent infertility due to an alternate medical cause other than the 
above (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), Investigator 
discretion should be applied to determining study entry. 
Note:  Documentation can come from the site personnel’s review of the participant’s medical records, 
medical examination, or medical history interview. 
• If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study product, additional evaluation should be considered. 
Woman of Nonchildbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 
1. Premenopausal female with permanent infertility due to one of the following: 
a. Documented hysterectomy 
b. Documented bilateral salpingectomy 
c. Documented bilateral oophorectomy 
d. For individuals with permanent infertility due to an alternate medical cause other than the above 
(e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), Investigator discretion 
should be applied to determining study entry. 
Note:  Documentation can come from the site personnel’s review of the participant’s medical records, 
medical examination, or medical history interview. 


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2. Postmenopausal female 
a. A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. 
i. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state 
in women not using hormonal contraception or HRT.  However, in the absence of 12 months of 
amenorrhea, confirmation with more than one FSH measurement is required. 
ii. Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 


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10.4.2 Contraception Guidance  
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of < 1% per year when used consistently and 
correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual partner of the woman of 
childbearing potential and the absence of sperm has been confirmed.  If not, an additional highly effective method of 
contraception should be used.  Spermatogenesis cycle is approximately 90 days. 
Note:  Documentation of azoospermia for a male participant can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of < 1% per year when used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
oral 
• 
injectable 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study product.  The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the study and the preferred and usual lifestyle of the participant. 
Effective Methodsd That Are Not Considered Highly Effective Failure rate of ≥ 1% per year when used consistently and 
correctly. 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action 
• 
Male or female condom with or without spermicide 
• 
Cervical cap, diaphragm, or sponge with spermicide 
• 
A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide (double-barrier methods)c 
a) Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for 
those participating in clinical studies. 
b) Failure rate of < 1% per year when used consistently and correctly.  Typical use failure rates differ from those when used 
consistently and correctly. 
c.) If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods 
are limited to those which inhibit ovulation as the primary mode of action.   
d) Considered effective, but not highly effective—failure rate of ≥ 1% per year.   
Note:  Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, 
and lactational amenorrhea method (LAM) are not acceptable methods of contraception.  Male condom and female condom 
should not be used together (due to risk of failure from friction). 


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10.5 Appendix 5:  Physician Global Assessment of Intertriginous Areas  
In this study, this PGA should be used only to assess plaque PSO in intertriginous areas (iPGA). 
Each assessment should be made as a visual “average” of the severity of all treated intertriginous 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, participant symptoms, or impact on participant’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 
Source:  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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10.8 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
   
  
 
 
 
 
  
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
   
  


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10.9 Appendix
  
 
 
 
   
 
  
 
 
  
 
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 


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SAP_001.pdf: 


Dermavant Sciences, Inc. 
 
Statistical Analysis Plan, v1.0 
DMVT-505-4001 
 
02JUN2023 
CONFIDENTIAL 
Page 2/19 
DMVT-505-4001_SAP_v1.0.docx 
SAP Signatures 
 
I give my approval for the SAP, including the table, listing, and figure shells, dated 02JUN2023. 
The analysis methods and data presentations are acceptable. 
 
 
Statistician (Author) 
Name: 
  
 
 
 
 
Title 
Senior Statistician 
 
 
Signature:
 
 
 
Date: 
 
 
 
 
 
 
 
 
 
Statistician Reviewer (As applicable) 
Name: 
  
 
 
 
Title 
Statistician 
 
 
 
Signature:
 
 
 
Date: 
 
 
 
 
 
 
 
 
 
Sponsor Approval 
Name: 
 
  
Title 
Director, Biostatistics 
 
Signature:
 
 
 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
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	
		
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  	 

  	 



Dermavant Sciences, Inc. 
 
Statistical Analysis Plan, v1.0 
DMVT-505-4001 
 
02JUN2023 
CONFIDENTIAL 
Page 3/19 
DMVT-505-4001_SAP_v1.0.docx 
TABLE OF CONTENTS 
VERSION HISTORY ......................................................................................................................5 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY OBJECTIVES ................................................................................................7 
2.1. 
Primary Objective .........................................................................................................7 
2.2. 
Secondary Objectives ...................................................................................................7 
2.3. 
Exploratory Objectives .................................................................................................7 
2.4. 
Safety Objectives ..........................................................................................................7 
3. 
STUDY DESIGN .........................................................................................................8 
3.1. 
Overall Design ..............................................................................................................8 
3.2. 
Study Assessments........................................................................................................9 
3.3. 
Assignment to Study Intervention ................................................................................9 
3.4. 
Blinding ........................................................................................................................9 
4. 
SAMPLE SIZE DETERMINATION ...........................................................................9 
5. 
STATISTICAL CONSIDERATIONS .........................................................................9 
5.1. 
General Considerations .................................................................................................9 
5.2. 
Analysis Populations ..................................................................................................10 
5.3. 
Analysis Windowing ..................................................................................................10 
5.4. 
Statistical Hypotheses .................................................................................................10 
5.5. 
Multiplicity Adjustment..............................................................................................11 
5.6. 
Missing Data ...............................................................................................................11 
5.7. 
Interim Analysis ..........................................................................................................11 
6. 
STUDY POPULATION .............................................................................................11 
6.1. 
Subject Disposition .....................................................................................................11 
6.2. 
Protocol Deviations ....................................................................................................11 
6.3. 
Eligibility ....................................................................................................................11 
6.4. 
Demographic and Baseline Characteristics ................................................................11 
6.5. 
Medical History ..........................................................................................................12 
6.6. 
Prior and Concomitant Therapy ..................................................................................12 
7. 
EFFICACY ANALYSES ...........................................................................................13 
7.1. 
Efficacy Endpoints ......................................................................................................13 
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	
		


Dermavant Sciences, Inc. 
 
Statistical Analysis Plan, v1.0 
DMVT-505-4001 
 
02JUN2023 
CONFIDENTIAL 
Page 4/19 
DMVT-505-4001_SAP_v1.0.docx 
7.2. 
Efficacy Analyses .......................................................................................................13 
7.3. 
 .............................................................................................................14 
8. 
SAFETY ASSESSMENTS ........................................................................................15 
8.1. 
Extent of Exposure .....................................................................................................15 
8.2. 
 ...........................................................................................................15 
8.3. 
17 
9. 
REPORTING CONVENTIONS ................................................................................18 
10. 
QUALITY ASSURANCE OF STATISTICAL PROGRAMMING ..........................18 
11. 
MODIFICATIONS .....................................................................................................18 
11.1. 
Modifications to Protocol-Specified Analyses ...........................................................18 
12. 
REFERENCES ...........................................................................................................19 
 
 
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VERSION HISTORY 
 
SAP Version 
Date 
Change 
Rationale 
1.0 
02JUN2023 
Not applicable 
Original version 
 
 
 
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Statistical Analysis Plan, v1.0 
DMVT-505-4001 
 
02JUN2023 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
ATC 
Anatomical/Therapeutic/ Chemical 
CCG 
eCRF Completion Guidelines 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
 
 
DMP 
Data Management Plan 
eCRF 
electronic Case Report Form 
ICH 
International Council for Harmonisation 
IND 
Investigational New Drug application 
iPGA 
intertriginous Physician Global Assessment 
ITT 
Intent-To-Treat 
LOCF 
Last Observation Carried Forward 
 
 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
OC 
Observed Cases 
PGA 
Physician Global Assessment 
 
 
 
 
PSO 
Plaque Psoriasis 
PT 
Preferred Term 
QD 
Once a Day 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedures 
 
 
TEAE 
Treatment-Emergent Adverse Event 
TLF 
Tables, Listings, and Figures 
USA 
United States of America 
USPI 
United States Prescribing Information 
VTAMA 
tapinarof 
WHO 
World Health Organization 
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Statistical Analysis Plan, v1.0 
DMVT-505-4001 
 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) for the final analysis is based on the most recent approved 
clinical study protocol (Version 1.0 dated on 14 October 2022), electronic case report form 
(eCRF)  (Version 1.1 dated on 09 February 2023), eCRF completion guidelines (CCG, Version 
2.0 dated on 10 March 2023), and Data Management Plan (DMP, Version 1.0 dated on 02 
November 2022).   
This SAP (Methods) documents the planned statistical analyses and data presentations for the 
final analysis of study DMVT-505-4001.  This SAP will be finalized and approved prior to the 
database lock. Any deviations from this plan will be documented in the clinical study report 
(CSR). 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of the study is to evaluate the efficacy of VTAMA (tapinarof) cream, 1% 
in adults with intertriginous PSO. 
2.2. 
Secondary Objectives 
The secondary objective of the study is to assess onset of effect of VTAMA (tapinarof) cream, 
1% in adults with intertriginous PSO. 
 
 
 
 
2.4. 
Safety Objectives 
The safety objective of the study is to evaluate the safety and tolerability of VTAMA (tapinarof) 
cream, 1% in adults with plaque PSO in intertriginous areas. 
 
 
 
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Statistical Analysis Plan, v1.0 
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3.2. 
Study Assessments 
Please refer to protocol Section 8 for descriptions of study procedures and assessments and 
protocol section 1.3 for timing of procedures and assessments (Schedule of Activities). 
3.3. 
Assignment to Study Intervention 
All subjects will be assigned to the study intervention of VTAMA (tapinarof) cream, 1% in the 
treatment of plaque PSO in intertriginous areas. 
3.4. 
Blinding 
This is an open-label study. 
4. 
SAMPLE SIZE DETERMINATION  
The sample size for this study is based on clinical considerations only. No formal sample size 
calculation will be performed. This study will enroll approximately 30 participants which is 
considered adequate to evaluate the efficacy and safety for the treatment of plaque PSO in the 
intertriginous areas. 
5. 
STATISTICAL CONSIDERATIONS 
5.1. 
General Considerations 
will perform the statistical analysis of the data. SAS version 9.4 or higher will be 
used to generate all statistical outputs (tables, listings, figures [TLFs], and datasets). The 
International Council for Harmonisation (ICH) numbering convention will be used for all TLFs. 
Continuous endpoints will be summarized by presenting the number of observations, means, 
standard deviations, medians, minimums, and maximums. The 95% confidence intervals will be 
reported as appropriate.  
Time to event analyses will use the Kaplan-Meier product limit method (if estimable) based on 
observed cases. 
Categorical endpoints will be summarized by presenting counts and percentages of subjects in 
corresponding categories. All possible categories as defined in the case report form (CRF) will 
be populated, even if they have zero counts. With the exception of ethnicity and race in the 
demographic table, percentages for missing values are omitted and do not account for the percent 
calculation of other categories. In certain tables (e.g., TEAEs), the total number of subjects is 
used as denominator. Footnotes will specify the percent basis in those cases. 
Individual subject data obtained from the eCRFs and any derived data will be presented by 
subject in data listings.  
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5.2. 
Analysis Populations 
The intent-to-treat (ITT) population will include all participants enrolled in the study.  
5.3. 
Analysis Windowing 
Study days are measured from date of first dose of study medication. Study days corresponding to 
measurements are calculated as:  
x 
Assessment date – date of first dose + 1 if assessment date is on or after the date of first 
exposure of treatment.  
x 
Assessment date – date of first dose if assessment date is before the date of first exposure of 
treatment.  
All efficacy and safety endpoints will be analyzed according to the nominal visits (i.e. actual visit) 
except for assessments collected on early termination and unscheduled visits. Early termination and 
unscheduled visits will be re-numbered to an analysis visit based on their windowed visits defined by 
actual study day. If more than one visit occurs within a single visit window, then the analysis will 
take the one closest to the target day. If the 2 visits are equidistant from the target day, the visit with 
later date and time will be used.  
The following analysis visit windows will apply to early termination and unscheduled visits: 
Analysis Visit 
Target Day 
Analysis Visit Window 
Baseline (1) 
1 
1 
Week 1 
8 
Post first dose to Day 12 
Week 2 
15 
Day 13 – Day 22 
Week 4 
29 
Day 23 – Day 36  
Week 6 
43 
Day 37 – Day 50 
Week 8 
57 
Day 51 – Day 71  
Week 12 
85 
Day 72 – Maximum (last day of 
treatment + 3 days, Day 87) 
Week 13 
92 
> Maximum (last day of 
treatment + 3 days , Day 87) 
5.4. 
Statistical Hypotheses 
Not applicable. Demographic and baseline characteristics, efficacy, safety,
 
 will be summarized descriptively. No inferential 
testing will be performed. 
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Statistical Analysis Plan, v1.0 
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5.5. 
Multiplicity Adjustment 
Not applicable 
5.6. 
Missing Data 
Every effort will be made to collect complete data at all visits.   
 
All efficacy data will be summarized based on observed cases (OC). 
Imputation of Missing Efficacy Data 
In addition to the efficacy analysis based on OC, the primary and exploratory efficacy endpoints 
will also be summarized utilizing the last observation carried forward (LOCF) method to impute 
missing data 
 
 Baseline will not be used when applying LOCF and LOCF will be 
implemented through Week 12 (i.e., Week 13 not included in LOCF). LOCF summaries will be 
considered supportive. 
5.7. 
Interim Analysis 
Not applicable 
6. 
STUDY POPULATION 
6.1. 
Subject Disposition 
Subject disposition information will be summarized and will include number of subjects 
screened, number of subjects included in the ITT population, the number of subjects completing 
the treatment phase of the study, the number of subjects completing the study through follow-up 
and primary reason for discontinuation. 
6.2. 
Protocol Deviations 
Protocol deviations will be summarized by deviation category (major, minor). Additionally, 
protocol deviations will be presented in a data listing. 
6.3. 
Eligibility 
Participants not fulfilling the eligibility criteria will be presented in a data listing. 
6.4. 
Demographic and Baseline Characteristics 
Demographic variables include age, sex, ethnicity, race, and Fitzpatrick skin type. Age will be 
reported on the CRF and will be based on age at time of signing informed consent. 
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Statistical Analysis Plan, v1.0 
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Baseline characteristics include intertriginous Physician Global Assessment (iPGA), 
 
 
 
Unless otherwise noted, baseline is defined as the last non-missing value recorded before the first 
dose of study drug. Unscheduled visits will be used in the determination of baseline values, when 
applicable. 
6.5. 
Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA, 
version 26.0). The summary will show the system organ class (SOC) and preferred terms (PT) 
ordered alphabetically by SOC and descending PT frequency.  The corresponding data listing by 
participant will be ordered by start date, end date, then alphabetically by preferred term. 
Psoriasis history in the intertriginous areas will be summarized by duration of disease (<5 years, 
5-10 years, >10 years) and by intertriginous areas affected. 
6.6. 
Prior and Concomitant Therapy 
Prior and concomitant medication verbatim terms will be mapped to Anatomical/Therapeutic/ 
Chemical (ATC) class and preferred names using the WHODrug global dictionary (Version B3 
01MAR2023). 
Prior (within the 30 days before screening, and with stop dates prior to first dose of study drug) 
and concomitant (ongoing or with stop dates on or after first dose of study drug) 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. 
To distinguish prior vs concomitant medications, the following rules for stop dates will apply: 
x If only year was recorded, and it is before Baseline, it is a prior medication; if year is 
same or after Baseline, it is assumed to be a concomitant medication.  
x If day is missing, but month and year are before Baseline, it is a prior medication; if 
month and year are the same as Baseline, it is assumed to be a concomitant medication; if 
month and year are after Baseline, it is a concomitant medication.  
x If start date is after Baseline, it is a concomitant medication regardless.  
Prior and concomitant medications will be summarized separately by WHO ATC 2 and preferred 
name. Subjects may have more than 1 medication per ATC 2 and preferred name. At each level 
of subject summarization, a subject is counted once if he/she reported 1 or more medications at 
that level. Frequencies and percentages of prior and concomitant medications will be ordered 
alphabetically by ATC class and descending preferred name. The corresponding data listing by 
participant will be ordered by start date of administration, end date of administration, then 
alphabetically by preferred name. 
 
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Statistical Analysis Plan, v1.0 
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8. 
SAFETY ASSESSMENTS 
8.1. 
Extent of Exposure  
The following exposure and compliance parameters will be summarized descriptively by 
treatment:  
x Total number of days exposed, defined as date of last dose of study drug - date of first 
dose of study drug + 1.  
x Number of doses administered, calculated from the in-clinic dose at Baseline and the 
subject dose diary. If a subject is exposed to study drug for more than 1 day, and 
returns no diary records, then the total number of doses is regarded to be missing. 
Otherwise, for any day for which there is no diary record, it is assumed that no study 
drug was administered at home.  
x Percent compliance will be calculated as the (Number of Doses Administered) / 
(Number of Days Exposed) * 100. Number of missed doses will be based on data 
from the summary of missed doses form.  
x 6XEMHFW FRPSOLDQFH GHILQHG DV  FRPSOLDQFH ZKLOH HQUROOHG LQ WKH VWXG\ ,I WKH
percentage of study medication compliance cannot be computed, the subject is 
assumed to be less than 80% compliant. 
$ VXEMHFW ZLOO EH FRPSOLDQW ZLWK WKH GRVLQJ UHJLPHQ LI WKH\ DSSOLHG  RI WKH H[SHFWHG GRVHV
Expected number of doses is based on length of time enrolled in the treatment-phase of the 
study.  
8.2. 
Adverse Events 
All AE summaries will be restricted to TEAEs, which are defined as those AEs that occurred 
after dosing and those pre-existing AEs (prior to first application of study treatment) that 
worsened during the study. If it cannot be determined whether the AE is treatment emergent due 
to a partial onset date, then it will be counted as TEAE. Verbatim terms in the eCRFs will be 
mapped to SOCs and PTs using MedDRA (Version 26.0).  
Imputation of start and end dates of AEs  
To calculate duration of AEs, the following rules will be used where applicable to impute partial 
or completely missing start dates or end dates:  
x 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 date of first dose, while the known month and year match 
the month and year of the first dose, the date of first dose will be used as the new 
estimated date. The AE will be considered as a treatment-emergent AE (TEAE).  
x 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. Last study visit is defined as the Week 13 visit.  
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Statistical Analysis Plan, v1.0 
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x 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. However, if the year of start is the same 
or greater than the year of the first dose date, the AE will be considered as a TEAE.  
x If the start date or end date is completely missing, duration will not be calculated. 
However, an event with completely missing start date will be considered as a TEAE.  
Imputation of missing relationship and/or missing severity  
If relationship to treatment is missing, the event will be conservatively treated as related to study 
drug.  
If severity is missing and the AE is reported as serious and fatal, severity will be imputed as 
CTCAE=5. If severity is missing and the AE is reported as serious and not fatal, severity will be 
imputed as CTCAE=4. If severity is missing and the AE is not reported as serious, severity will 
be imputed as CTCAE=3.  
All AEs will be listed by subject, detailing the verbatim term given by the investigator, the SOC, 
PT, onset date and time, end date and time, duration (days), common terminology criteria for 
adverse events (CTCAE) grade, outcome, relationship to study drug, action taken with study 
drug, other action taken to treat the event, seriousness, and criteria for seriousness. Serious AEs 
(SAEs), TEAEs related to study drug, TEAEs leading to study drug discontinuation, and TEAEs 
leading to study discontinuation will also be listed separately.  
All AE will be summarized using frequency counts and percentages:  
x Any TEAEs 
x Related TEAEs 
x TEAEs leading to study treatment discontinuation 
x TEAEs leading to discontinuation from study 
x Any Serious TEAE (non-Fatal) 
x Any Serious TEAE (All) 
x Death 
x Treatment-related Serious TEAE 
x Serious TEAE leading to study treatment discontinuation 
x Serious TEAE leading to discontinuation from study 
TEAEs will be ordered alphabetically by MedDRA SOC and by descending PT frequency. 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 
manner. For summaries of relationship to study drug, a subject will be classified according 
related or not related. For summaries of TEAE CTCAE grade, a subject will be classified 
according to the worst grade. 
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8.3. 
 
 
 
 
 
 
 
 
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9. 
REPORTING CONVENTIONS 
Means and medians will be presented to 1 more decimal place than the raw data. Standard 
deviations will be presented to 2 more decimal places than the raw data. Minimums and 
maximums will be reported with the same number of decimal places as the raw data. Percentiles 
(eg, 25%, median, 75%) will be presented to 1 decimal place more than the raw/derived data.  
10. 
QUALITY ASSURANCE OF STATISTICAL PROGRAMMING 
 Standard Operating Procedures (SOPs) governing the statistical analysis and 
programming will be followed.  
11. 
MODIFICATIONS   
11.1. 
Modifications to Protocol-Specified Analyses 
Week 13 will be included in the summaries of iPGA, 
.  
 
 
 
 
 
 
 
 
 
 
 
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