Maximal Use Study of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis

Open Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis

This is an open-label, multicenter study to evaluate the systemic exposure and safety of topical tapinarof cream, 1% under conditions of maximal use in pediatric subjects with atopic dermatitis

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Tapinarof cream, 1%

Detailed Description

This is a 4-week open-label study in which subjects will be assigned to receive tapinarof cream, 1% once daily for 4 weeks. At the end of the 4-week study treatment, qualified subjects will have the option to enroll in an open-label, long-term extension study for an additional 48 weeks of treatment. Subjects who do not participate in the open-label, long-term extension study will complete a follow-up visit approximately one week after the end of treatment in this study.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Dermavant Investigative Site
• United States
  • California
    • Thousand Oaks, California, United States, 91320
      • Dermavant Investigative Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Dermavant Investigative Site
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Dermavant Investigative Site
    • Hialeah, Florida, United States, 33016
      • Dermavant Investigative Site
    • Miami Lakes, Florida, United States, 33014
      • Dermavant Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Dermavant Investigative Site
  • South Carolina
    • Summerville, South Carolina, United States, 29445
      • Dermavant Investigative Site
  • Texas
    • Houston, Texas, United States, 77030
      • Dermavant Investigative Site
    • San Antonio, Texas, United States, 78213
      • Dermavant Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female subjects age 2 to 17 with a confirmed clinical diagnosis of atopic dermatitis and present for at least 6 months for ages 6-17 years old, 3 months for ages 2-5 years old
• BSA involvement ≥ 25% for subjects ages 12-17 years old, or ≥ 35% for subjects ages 2-11 years old, suitable for topical therapy.
• vIGA-AD score of ≥ 3 at screening and baseline (pre-dose)
• Female subjects of child bearing potential who are engaging in sexual activity that could lead to pregnancy agree to follow the specified contraceptive guidance throughout the study
• Capable of giving written informed consent
• Negative pregnancy test at Baseline (Day 1)

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tapinarof cream; Tapinarof (DMVT-505) cream, 1% applied topically once daily	Drug: Tapinarof cream, 1%; Tapinarof cream, 1% applied topically once daily; Other Names: DMVT-505

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs).	Baseline to Day 28 for subjects enrolling in Long-Term Extension (LTE), otherwise to Day 35
Change From Baseline in Laboratory Values (U/L)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (g/L)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (mmol/L)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (Umol/L)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (10^9 Cells/L)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (%)	Change in laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (pg)	Change in Ery. mean corpuscular hemoglobin laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (fL)	Change in Ery. mean corpuscular volume laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (10^12 Cells/L)	Change in Erythrocytes laboratory values was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Laboratory Values (L/L)	Change in Hematocrit laboratory values was assessed for clinical relevance	Baseline to Day 28
Mean Change in Local Tolerability Scale (LTS)	Local Tolerability Scale (LTS) is a clinical tool for assessing the presence and overall degree of irritation at the application sites, according to a 5-point scale. 0 indicates no irritation and 4 indicates Very Severe irritation.	Baseline to Day 28
Tapinarof Plasma PK Parameters on Day 1: AUC0-τ	The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Tapinarof Plasma PK Parameters on Day 1: Cmax	The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Tapinarof Plasma PK Parameters on Day 1: Tmax	The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Tapinarof Plasma Concentration: Cτ	The Cτ is a pharmacokinetic parameter that is the last quantifiable concentration determined directly from individual concentration-time data	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)
Change From Baseline in Vital Signs (Beats/Min)	Change in pulse vital signs was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Vital Signs (mmHg)	Change in Blood Pressure vital signs was assessed for clinical relevance	Baseline to Day 28
Change From Baseline in Vital Signs (C)	Change in Temperature vital signs was assessed for clinical relevance	Baseline to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)	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.	Baseline to Day 28
Number of Subjects Who Have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Score of Almost Clear (0 or 1) and at Least a 2-grade Reduction From Baseline	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.	Baseline to Day 28
Number of Subjects With ≥50%, Improvement in Eczema Area and Severity Index (EASI) Score	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.	Baseline to Day 28
Number of Subjects With ≥75%, Improvement in Eczema Area and Severity Index (EASI) Score	The EASI is a composite score ranging from 0 to 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 %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Number of Subjects With ≥90%, Improvement in Eczema Area and Severity Index (EASI) Score	The EASI is a composite score ranging from 0 to 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 %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Mean Change in Eczema Area and Severity Index EASI From Baseline to Day 28	The EASI is a composite score ranging from 0 to 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 %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Percent Change in Eczema Area and Severity Index EASI From Baseline to Day 28	The EASI is a composite score ranging from 0 to 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 %BSA involved for each body region relative to the whole body. Higher EASI scores indicate more severe disease.	Baseline to Day 28
Mean Change in Percent of Total Body Surface Area (%BSA) Affected	The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.	Baseline to Day 28
Percent Change in Percent of Total Body Surface Area (%BSA) Affected	The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores.	Baseline to Day 28
Mean Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values	The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting (0 indicates no inflammatory signs of atopic dermatitis and 4 indicates disease is widespread). The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. %BSA is a static assessment made without reference to previous scores and will be evaluated 0-100%. The computation is referenced below, and no unit is applicable for this outcome measure. A negative change indicates improvement in disease. [Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)]	Baseline to Day 28
Percent Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values	The vIGA-AD is a clinical tool for assessing the current state/severity of a subject's atopic dermatitis at a given timepoint. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Score of 0 indicates no inflammatory signs of atopic dermatitis and a 4 indicates disease is widespread in extent. The assessment of %BSA affected is an estimate of the percentage of total involved skin with psoriasis. For the purpose of clinical estimation, the total palmar surface of the subject's palm and digits may be assumed to be approximately equivalent to 1% BSA. The %BSA affected by psoriasis will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. Computation: Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)	Baseline to Day 28
Mean Change in Average Weekly Peak Pruritus Numerical Rating Scale (PP-NRS) Score	The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.	Baseline to Day 28
Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score	The PP-NRS is a scale from 0-10 used to assess itch/pruritus severity over a 24-hour period which will be used daily to assess peak pruritus. Higher PP-NRS ratings represent more itch reported.	Baseline to Day 28

Collaborators and Investigators

• Sponsor: Organon and Co
• Investigators: Study Director: Diana Villalobos, Dermavant Sciences, Inc.

Publications and helpful links

General Publications

• Bieber T. Atopic dermatitis. N Engl J Med. 2008 Apr 3;358(14):1483-94. doi: 10.1056/NEJMra074081. No abstract available.
• Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005 May-Jun;22(3):192-9. doi: 10.1111/j.1525-1470.2005.22303.x.
• Bashaw ED, Tran DC, Shukla CG, Liu X. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products. Ther Innov Regul Sci. 2015 Jan;49(1):108-115. doi: 10.1177/2168479014539157. Epub 2014 Jun 27.
• Cappon GD and Hurtt ME. Developmental toxicity of the kidney. In: Kapp RW and Yyl L, editors. Reproductive Toxicology, Target Organ Series, 3rd edition. New York:Informa Healthcare, 2010:193-204.
• Frazier KS and Seely JC. Urinary system. In: Sahota PS, Popp JA, Hardisty JF and Gopinath C, editors. Toxicologic Pathology. Nonclinical Safety Assessment. CRC Press, 2013:421-84.
• Furue M, Hashimoto-Hachiya A, Tsuji G. Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. Int J Mol Sci. 2019 Oct 31;20(21):5424. doi: 10.3390/ijms20215424.
• Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermato-Venereologica Supplementum. 1980;92:44-7.
• Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group. Exp Dermatol. 2001 Feb;10(1):11-8. doi: 10.1034/j.1600-0625.2001.100102.x.
• Kalia YN, Nonato LB, Lund CH, Guy RH. Development of skin barrier function in premature infants. J Invest Dermatol. 1998 Aug;111(2):320-6. doi: 10.1046/j.1523-1747.1998.00289.x.
• Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract. 2006 Aug;60(8):984-92. doi: 10.1111/j.1742-1241.2006.01047.x.
• Nikolovski J, Stamatas GN, Kollias N, Wiegand BC. Barrier function and water-holding and transport properties of infant stratum corneum are different from adult and continue to develop through the first year of life. J Invest Dermatol. 2008 Jul;128(7):1728-36. doi: 10.1038/sj.jid.5701239. Epub 2008 Jan 17.
• Peppers J, Paller AS, Maeda-Chubachi T, Wu S, Robbins K, Gallagher K, Kraus JE. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J Am Acad Dermatol. 2019 Jan;80(1):89-98.e3. doi: 10.1016/j.jaad.2018.06.047. Epub 2018 Jul 3.
• Smith SH, Jayawickreme C, Rickard DJ, Nicodeme E, Bui T, Simmons C, Coquery CM, Neil J, Pryor WM, Mayhew D, Rajpal DK, Creech K, Furst S, Lee J, Wu D, Rastinejad F, Willson TM, Viviani F, Morris DC, Moore JT, Cote-Sierra J. Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. J Invest Dermatol. 2017 Oct;137(10):2110-2119. doi: 10.1016/j.jid.2017.05.004. Epub 2017 Jun 6.
• Zoetis T, Hurtt ME. Species comparison of anatomical and functional renal development. Birth Defects Res B Dev Reprod Toxicol. 2003 Apr;68(2):111-20. doi: 10.1002/bdrb.10013. No abstract available.
• Paller AS, Hebert AA, Gonzalez ME, Butners V, Fitzgerald N, Tabolt G, Rubenstein DS, Piscitelli SC. Maximal Usage Trial of Tapinarof Cream 1% Once Daily in Pediatric Patients Down to 2 Years of Age with Extensive Atopic Dermatitis. Am J Clin Dermatol. 2025 May;26(3):449-456. doi: 10.1007/s40257-025-00929-9. Epub 2025 Mar 24.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): August 24, 2022
• Study Completion (Actual): August 24, 2022

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: eczema; pediatric; topical; phase 2; tapinarof
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic; Eczema
• Other Study ID Numbers: DMVT-505-2104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No