Clinical trial NCT05186805: Maximal Use Study of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis
Official title: Open Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Pediatric Subjects With Extensive Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: eczema
pediatric
tapinarof
phase 2
topical
Lead sponsor: Dermavant Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-11
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline to Day 28
measure: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Values and Vital Signs
timeFrame: Baseline to Day 28
measure: Number of participants with irritation as assessed by the Local Tolerability Scale (LTS)
timeFrame: Baseline to Day 28
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: AUC0-τ
timeFrame: Day 1 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing)
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: Cmax
timeFrame: Day 1 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing)
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1: tmax
timeFrame: Day 1 and Day 28 (PK sample collected at pre-dose and at 1, 3, and 5 hours after dosing)
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma concentration on Day 28: Cτ
timeFrame: Day 28 (PK sample collected approximately 24 hours after the last dose)
Secondary outcomes:
measure: Change from Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)
timeFrame: Baseline to Day 28
measure: Number of subjects who have a Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) score of almost clear (0 or 1) from baseline to Day 28
timeFrame: Baseline to Day 28
measure: Number of subjects with ≥50%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit
timeFrame: Baseline to Day 28
measure: Number of subjects with ≥75%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit
timeFrame: Baseline to Day 28
measure: Number of subjects with ≥90%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit
timeFrame: Baseline to Day 28
measure: Mean change in Eczema Area and Severity Index EASI from baseline to Day 28
timeFrame: Baseline to Day 28
measure: Mean change in Percent of Total Body Surface Area (%BSA) affected from Baseline to Day 28
timeFrame: Baseline to Day 28
measure: Mean change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) values form Baseline to Day 28
timeFrame: Baseline to Day 28
measure: Mean change in average weekly Peak Pruritus Numerical Rating Scale (PP-NRS) score by age group from Baseline to Day 28
timeFrame: Baseline to Day 28
measure: Proportion of subjects with a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) score ≥4-point reduction in PP-NRS score from Baseline to Day 28
timeFrame: Baseline to Day 28
Other outcomes:
Locations:
city: Thousand Oaks
country: United States
facility: Dermavant Investigative Site
state: California
city: Centennial
country: United States
facility: Dermavant Investigative Site
state: Colorado
city: Coral Gables
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Miami Lakes
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Chicago
country: United States
facility: Dermavant Investigative Site
state: Illinois
city: Summerville
country: United States
facility: Dermavant Investigative Site
state: South Carolina
city: Houston
country: United States
facility: Dermavant Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Dermavant Investigative Site
state: Texas
city: Calgary
country: Canada
facility: Dermavant Investigative Site
state: Alberta
Study officials:
affiliation: Dermavant Sciences, Inc.
name: Diana Villalobos
role: STUDY_DIRECTOR
References:
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citation: 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.
citation: 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.
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