Tapinarof for the Treatment of Atopic Dermatitis in Child... | NCT05014568

Label	Type	Description	Intervention Names
tapinarof cream	Experimental	tapinarof cream, 1%, applied topically once daily	Drug: tapinarof cream, 1%
vehicle cream	Placebo Comparator	vehicle cream, applied topically once daily	Drug: Vehicle cream

Name	Type	Description	Arm Group Labels	Other Names
tapinarof cream, 1%	Drug	applied topically once daily	tapinarof cream

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.	The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease. Statistics are based on 100 imputed datasets.	Baseline to Week 8

Secondary Outcomes

Measure	Description	Time Frame
Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.	The Eczema Area and Severity Index (EASI) is a scoring system that takes into account the overall severity of disease based on lesion severity and the extent of percent body surface area affected with atopic dermatitis. The EASI is a composite score ranging from 0 -72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the percent body surface area involved for each body region relative to the whole body. A higher EASI score represents more severe disease. Statistics are based on 100 imputed datasets.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female subjects ages 2 and above with clinical diagnosis of AD
Subject with atopic dermatitis covering ≥5% and ≤ 35% of the BSA
A vIGA-AD score of ≥3 at screening and baseline
An EASI score of ≥6 at screening and baseline
Atopic dermatitis present for at least 6 months for ages 6 years old and above or 3 months for ages 2 to 5 years old
Female subjects of childbearing potential who are engaging in sexual activity that could lead to pregnancy should use acceptable birth control methods
Must not be pregnant
Subject, subject's parent, or legal representative must be capable of giving written informed consent/assent

Exclusion Criteria:

Immunocompromised at screening
Chronic or acute systemic or superficial infection requiring treatment with systemic antibacterials or antifungals within one week prior to baseline visit
Significant dermatological or inflammatory condition other than AD that, in the Investigator's opinion, would make it difficult to interpret data or assessments during the study
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.0x the upper limit of normal (ULN).
Screening total bilirubin > 1.5x ULN
Current or chronic history of liver disease
Current or history of cancer within 5 years except for adequately treated cutaneous basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix
Subjects who would not be considered suitable for topical therapy
Use of any prohibited medication or procedure within the indicated period before the baseline visit including other investigational product within 30 days or 5 half-lives of the investigational product (whichever is longer)
History of or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the Investigator's opinion, may interfere with the subject's participation in the study, interpretation of results, or ability to understand and give informed consent.
Pregnant or lactating females
History of sensitivity to the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation
Previous known participation in a clinical study with tapinarof (previously known as GSK2894512 and WBI-1001)

Name	Affiliation	Role
Diana Villalobos	Dermavant Sciences, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Dermavant Investigative Site		Birmingham	Alabama	35244	United States
Dermavant Investigative Site

PubMed Identifier	Type	Citation	Retractions
38777187	Result	Silverberg JI, Eichenfield LF, Hebert AA, Simpson EL, Stein Gold L, Bissonnette R, Papp KA, Browning J, Kwong P, Korman NJ, Brown PM, Rubenstein DS, Piscitelli SC, Somerville MC, Tallman AM, Kircik L. Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials. J Am Acad Dermatol. 2024 Sep;91(3):457-465. doi: 10.1016/j.jaad.2024.05.023. Epub 2024 May 20.
40696240

ID	Title	Description
FG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
FG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 9, 2022	Jan 13, 2025

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00015.6± 16.62 BG00115.6± 16.49 BG00215.6± 16.56

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

2-6 Years

Title	Measurements
	BG00076 BG00139 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000140 BG00171 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00054 BG00144 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0002 BG0010 BG002

Region of Enrollment

Number

Count of participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG00040 BG00112 BG002

Validated Investigator Global Assessment for Atopic Dermatitis

Grading (per protocol score definition):

0: Clear - No inflammatory signs of atopic dermatitis.

Almost Clear - Barely perceptible erythema, induration/papulation, and/or minimal lichenification.
Mild - Slight but definite erythema (pink), slight but definite induration/papulation, and/or slight but definite lichenification.
Moderate - Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, and/or clearly perceptible lichenification.
Severe - Marked erythema (deep or bright red), marked induration/papulation, and/or marked lichenification.

Count of Participants

Participants

Title

Denominators

Categories

0 - Clear

Title	Measurements
	BG0000 BG001

Percent Body Surface Area (BSA)

Mean

Standard Deviation

Percentage of Affected BSA

Title

Denominators

Categories

Title	Measurements
	BG00016.45± 8.666 BG00117.71± 9.500 BG002

Eczema Area and Severity Index (EASI)

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG00012.24± 5.007 BG00112.86± 5.633 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent of Subjects Who Have a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of Clear or Almost Clear (0 or 1) With a Minimum 2-grade Improvement From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.

The vIGA-AD is a global assessment of the current state of the disease. It is a static 5-point scale used to grade overall disease severity (scalp excluded), as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. The vIGA-AD ranges from 0 to 4 and is calculated as Clear (0), Almost clear (1), Mild (2), Moderate (3), and Severe (4). Higher vIGA-AD scores represent more severe disease.

Statistics are based on 100 imputed datasets.

ITT Population (MI Estimand)

Posted

Number

Percentage of participants

Baseline to Week 8

ID	Title	Description
OG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
OG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Units	Counts
Participants	OG000270 OG001137

Title

Denominators

Categories

Title	Measurements
	OG00045.4 OG00113.9

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	H0: The proportion of subjects who achieve a vIGA-AD score of clear (0) or almost clear (1) and at least a 2-grade reduction from Baseline at Week 8 is equal between tapinarof cream, 1% and vehicle cream; H1: The proportion of subjects who achieve a vIGA-AD score of clear (0) or almost clear (1) and at least a 2-grade reduction from Baseline at Week 8 is different between the tapinarof cream, 1% and vehicle cream.	Cochran-Mantel-Haenszel	Stratified by Baseline vIGA-AD Score and Age Group	<0.0001		Risk Ratio, log	2.60			2-Sided	95	1.66	4.09			Adjusted logit-based estimate of the common relative risk of success (Tapinarof Cream 1%/Vehicle Cream) over all strata. Multiple imputation p-value is for null hypothesis that the log (Relative Risk) equals 0.

Secondary

Percent of Subjects With ≥ 75% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.

The Eczema Area and Severity Index (EASI) is a scoring system that takes into account the overall severity of disease based on lesion severity and the extent of percent body surface area affected with atopic dermatitis. The EASI is a composite score ranging from 0 -72 that takes into account the degree of erythema, edema/papulation, excoriation, and lichenification (each scored from 0 to 3 separately) for each of four body regions, with adjustment for the percent body surface area involved for each body region relative to the whole body. A higher EASI score represents more severe disease.

Statistics are based on 100 imputed datasets.

ITT Population (MI Estimand)

Posted

Number

Percentage of participants

Baseline to Week 8

ID	Title	Description
OG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
OG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Units	Counts

Secondary

Mean Change in in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 8.

Assessment of percent body surface area (%BSA) is an estimate of the percentage of total involved skin with atopic dermatitis. Estimates were made using the handprint method, where the full palmar hand of the participant (fully extended palm, fingers and thumbs together) represented approximately 1% of the total BSA. Body regions are assigned a specific number of handprints with associated percentages (Head and neck = 10% [10 handprints], upper extremities = 20% [20 handprints], trunk (including axillae and groin) = 30% [30 handprints], lower extremities, including buttocks, = 40% [40 handprints]). Estimates of the percent involvement of each body region will be multiplied by the fraction of total body area to obtain the total %BSA involved by region and overall.

ITT Population (MI Estimand)

Posted

Mean

Standard Error

change in affected BSA percentage

Baseline to Week 8

ID	Title	Description
OG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
OG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Secondary

Percent of Subjects With ≥ 90% Improvement in Eczema Area and Severity Index (EASI) From Baseline to Week 8. Analyses Were Done Using Multiple Imputation.

Statistics are based on 100 imputed datasets.

ITT Population (MI Estimand)

Posted

Number

Percentage of participants

Baseline to Week 8

ID	Title	Description
OG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
OG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Units	Counts

Secondary

Percent of Subjects ≥ 12 Years Old With a Baseline Peak Pruritis-Numeric Rating Scale (PP-NRS) Score ≥ 4 Who Achieve ≥ 4-point Reduction in the Average Weekly PP-NRS From Baseline to Week 8.

The Peak Pruritus Numeric Rating Scale (PP-NRS) is used to quickly assess itch/pruritus severity over a 24-hour period. The PP-NRS is scored on a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". The subject will utilize the scale to assess peak pruritis once per day and record the results in their diaries. The daily ratings are averaged to generate a score for the week.

Statistics are based on 100 imputed datasets.

ITT Population (MI Estimand) - subjects ≥ 12 years old with a Baseline PP-NRS score ≥ 4

Posted

Number

Percentage of participants

Baseline to Week 8

ID	Title	Description
OG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
OG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG00015 events10 affected270 at risk EG0011 events1 affected137 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected270 at risk EG0010 events0 affected137 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0011 events1 affected137 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected270 at risk EG0012 events2 affected137 at risk
Pyrexia	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events5 affected270 at risk EG0013 events3 affected137 at risk
Application site pain	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events3 affected270 at risk EG0010 events0 affected137 at risk
Folliculitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG00022 events22 affected270 at risk EG0011 events1 affected137 at risk
Nasopharyngitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG00013 events13 affected270 at risk EG0017 events7 affected137 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG00013 events13 affected270 at risk EG0010 events0 affected137 at risk
COVID-19	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0007 events7 affected270 at risk EG0015 events5 affected137 at risk
Influenza	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0006 events6 affected270 at risk EG0011 events1 affected137 at risk
Application site folliculitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Sinusitis	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0005 events4 affected270 at risk EG0010 events0 affected137 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Skim papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Headache	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG00020 events19 affected270 at risk EG0013 events3 affected137 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0006 events6 affected270 at risk EG0011 events1 affected137 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected270 at risk EG0011 events1 affected137 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected270 at risk EG0013 events3 affected137 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0004 events4 affected270 at risk EG0012 events2 affected137 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0003 events3 affected270 at risk EG0010 events0 affected137 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 events1 affected270 at risk EG0013 events3 affected137 at risk

ID	Term
D012873	Skin Diseases, Genetic
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D003872	Dermatitis
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D017443	Skin Diseases, Eczematous
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily
BG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Tapinarof Cream	tapinarof cream, 1%, applied topically once daily tapinarof cream, 1%: applied topically once daily	0	270	3	270	118	270
EG001	Vehicle Cream	vehicle cream, applied topically once daily Vehicle cream: applied topically once daily	0	137	0	137	33	137