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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tapinarof cream, 1%


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tapinarof cream<br>Tapinarof (DMVT-505) cream, 1% applied topically once daily | Drug: Tapinarof cream, 1%<br>* Tapinarof cream, 1% applied topically once daily<br>* Other names: DMVT-505;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs) | Frequency, Severity, and Duration AEs (local and systemic) | Baseline to Day 28 | 
| Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Values and Vital Signs | Change in laboratory values and vial signs were assessed for clinical relevance | Baseline to Day 28 | 
| Number of participants with irritation as assessed by the 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 and Tapinarof Sulfate (Metabolite) 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 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing) | 
| Tapinarof and Tapinarof Sulfate (Metabolite) 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 and Day 28 (PK samples collected at pre-dose and at 1, 3, and 5 hours after dosing) | 
| Tapinarof and Tapinarof Sulfate (Metabolite) 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 and Day 28 (PK sample collected at pre-dose and at 1, 3, and 5 hours after dosing) | 
| Tapinarof and Tapinarof Sulfate (Metabolite) Plasma concentration on Day 28: Cτ | The Cτ is a pharmacokinetic parameter that describes the time of last quantifiable concentration that is achieved after the last dose. | Day 28 (PK sample collected approximately 24 hours after the last dose) | 

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 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. | 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) from baseline to Day 28 | 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. | Baseline to Day 28 | 
| Number of subjects with ≥50%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit | 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 ≥75%, improvement in Eczema Area and Severity Index (EASI) score from Baseline to each visit | 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 from Baseline to each visit | 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 | 
| Mean change in Percent of Total Body Surface Area (%BSA) affected from Baseline to Day 28 | 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 form Baseline to Day 28 | 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. | Baseline to Day 28 | 
| Mean change in average weekly Peak Pruritus Numerical Rating Scale (PP-NRS) score by age group from Baseline to Day 28 | 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-point reduction in PP-NRS score from Baseline to Day 28 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eczema, pediatric, tapinarof, phase 2, topical