Tapinarof for the Treatment of Atopic Dermatitis in Children and Adults (DMVT-505-3102)

A Phase 3 Efficacy and Safety Study of Tapinarof for the Treatment of Moderate to Severe Atopic Dermatitis in Children and Adults

This is a double-blind, randomized, vehicle controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% compared to vehicle control cream in pediatric and adult subjects with atopic dermatitis.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: tapinarof cream, 1%; Drug: vehicle cream

Detailed Description

This study is a 8-week double-blind, vehicle-controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 8 weeks. At the end of the 8-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): 406
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Philip Brown, MD, JD; Phone Number: 480-666-0844; Email: dermavantclinicaltrials@dermavant.com

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Dermavant Investigative Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Dermavant Investigative Site
    • Markham, Ontario, Canada, L3P 1X3
      • Dermavant Investigative Site
    • Waterloo, Ontario, Canada, N2J 1C4
      • Dermavant Investigative Site
    • Windsor, Ontario, Canada, N8W 1E6
      • Dermavant Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Dermavant Investigative Site
  • Arizona
    • Scottsdale, Arizona, United States, 85255
      • Dermavant Investigative Site
    • Scottsdale, Arizona, United States, 85260
      • Dermavant Investigative Site
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • Dermavant Investigative Site
  • California
    • Cerritos, California, United States, 90702
      • Dermavant Investigative Site
    • Huntington Beach, California, United States, 92647
      • Dermavant Investigative Site
    • Lancaster, California, United States, 93534
      • Dermavant Investigative Site
    • Long Beach, California, United States, 90806
      • Dermavant Investigative Site
    • Los Angeles, California, United States, 90045
      • Dermavant Investigative Site
    • San Diego, California, United States, 92123
      • Dermavant Investigative Site
    • San Francisco, California, United States, 94115
      • Dermavant Investigative Site
    • Santa Ana, California, United States, 92701
      • Dermavant Investigative Site
    • Santa Monica, California, United States, 90404
      • Dermavant Investigative Site
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Dermavant Investigative Site
    • Delray Beach, Florida, United States, 33484
      • Dermavant Investigative Site
    • Jacksonville, Florida, United States, 32256
      • Dermavant Investigative Site
    • Miami, Florida, United States, 33165
      • Dermavant Investigative Site
    • Miami, Florida, United States, 33173
      • Dermavant Investigative Site
    • Miami Lakes, Florida, United States, 33014
      • Dermavant Investigative Site
    • Tampa, Florida, United States, 33607
      • Dermavant Investigative Site
  • Georgia
    • Snellville, Georgia, United States, 30078
      • Dermavant Investigative Site
  • Indiana
    • Evansville, Indiana, United States, 47715
      • Dermavant Investigative Site
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Dermavant Investigative Site
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Dermavant Investigative Site
    • Louisville, Kentucky, United States, 40241
      • Dermavant Investigative Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Dermavant Investigative Site
    • Baton Rouge, Louisiana, United States, 70808
      • Dermavant Investigative Site
    • New Orleans, Louisiana, United States, 70115
      • Dermavant Investigative Site
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Dermavant Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Dermavant Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Dermavant Investigative Site
    • Omaha, Nebraska, United States, 68114
      • Dermavant Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Dermavant Investigative Site
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • Dermavant Investigative Site
  • New York
    • Brooklyn, New York, United States, 11203
      • Dermanvant Investigative Site
    • Watertown, New York, United States, 13601
      • Dermavant Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Dermavant Investigative Site
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Dermavant Investigative Site
    • Mason, Ohio, United States, 45040
      • Dermavant Investigative Site
    • Mayfield Heights, Ohio, United States, 44124
      • Dermavant Investigative Site
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74114
      • Dermavant Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Dermavant Investigative Site
    • Portland, Oregon, United States, 97210
      • Dermavant Investigative Site
    • Portland, Oregon, United States, 97239
      • Dermavant Investigative Site
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Dermavant Investigative Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Dermavant Investigative Site
    • North Charleston, South Carolina, United States, 29420
      • Dermavant Investigative Site
    • Spartanburg, South Carolina, United States, 29303
      • Dermavant Investigative Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Dermavant Investigative Site
  • Texas
    • Bellaire, Texas, United States, 77401
      • Dermavant Investigative Site
    • Dripping Springs, Texas, United States, 78620
      • Dermavant Investigative Site
    • Grapevine, Texas, United States, 76051
      • Dermavant Investigative Site
    • Houston, Texas, United States, 77004
      • Dermavant Investigative Site
    • Houston, Texas, United States, 77061
      • Dermavant Investigative Site
    • San Antonio, Texas, United States, 78213
      • Dermavant Investigative Site
    • Webster, Texas, United States, 77598
      • Dermavant Investigative Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Dermavant Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tapinarof cream; tapinarof cream, 1%, applied topically once daily	Drug: tapinarof cream, 1%; applied topically once daily
Placebo Comparator: vehicle cream; vehicle cream, applied topically once daily	Drug: vehicle cream; applied topically once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	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.	Baseline to Week 8
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.	Baseline to Week 8
Percent of subjects with ≥ 90% 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.	Baseline to Week 8
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.	Baseline to Week 8

Collaborators and Investigators

• Sponsor: Dermavant Sciences GmbH
• Investigators: Study Director: Diana Villalobos, Dermavant Sciences, Inc.

Publications and helpful links

General Publications

• Basra MK, Salek MS, Camilleri L, Sturkey R, Finlay AY. Determining the minimal clinically important difference and responsiveness of the Dermatology Life Quality Index (DLQI): further data. Dermatology. 2015;230(1):27-33. doi: 10.1159/000365390. Epub 2015 Jan 20.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermato-Venereologica Supplementum. 1980;92:44-7.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2021
• Primary Completion (Actual): February 3, 2023
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: eczema; pediatric; topical; phase 3; tapinarof
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: DMVT-505-3102

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