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

Phase 2

Completed

Conditions: Atopic Dermatitis

Interventions: Drug: Tapinarof cream, 1%

Registration Number: NCT05186805

Lead Sponsor: Organon and Co

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
tapinarof cream	Tapinarof cream, 1%	Tapinarof (DMVT-505) cream, 1% applied topically once daily

Primary Outcome Measures

Name	Time	Method
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	Number of Participants that Experienced Adverse Events (AEs) and Serious Adverse Events (SAEs).
Change From Baseline in Laboratory Values (U/L)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (g/L)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (mmol/L)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (Umol/L)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (10^9 Cells/L)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (%)	Baseline to Day 28	Change in laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (pg)	Baseline to Day 28	Change in Ery. mean corpuscular hemoglobin laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (fL)	Baseline to Day 28	Change in Ery. mean corpuscular volume laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (10^12 Cells/L)	Baseline to Day 28	Change in Erythrocytes laboratory values was assessed for clinical relevance
Change From Baseline in Laboratory Values (L/L)	Baseline to Day 28	Change in Hematocrit laboratory values was assessed for clinical relevance
Mean Change in Local Tolerability Scale (LTS)	Baseline to Day 28	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.
Tapinarof Plasma PK Parameters on Day 1: AUC0-τ	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)	The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.
Tapinarof Plasma PK Parameters on Day 1: Cmax	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)	The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.
Tapinarof Plasma PK Parameters on Day 1: Tmax	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)	The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.
Tapinarof Plasma Concentration: Cτ	Day 1 (PK samples collected pre-dose and at 1, 3, and 5 hours post-dose)	The Cτ is a pharmacokinetic parameter that is the last quantifiable concentration determined directly from individual concentration-time data
Change From Baseline in Vital Signs (Beats/Min)	Baseline to Day 28	Change in pulse vital signs was assessed for clinical relevance
Change From Baseline in Vital Signs (mmHg)	Baseline to Day 28	Change in Blood Pressure vital signs was assessed for clinical relevance
Change From Baseline in Vital Signs (C)	Baseline to Day 28	Change in Temperature vital signs was assessed for clinical relevance

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)	Baseline to Day 28	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.
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	Baseline to Day 28	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.
Number of Subjects With ≥50%, Improvement in Eczema Area and Severity Index (EASI) Score	Baseline to Day 28	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.
Number of Subjects With ≥75%, Improvement in Eczema Area and Severity Index (EASI) Score	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.
Number of Subjects With ≥90%, Improvement in Eczema Area and Severity Index (EASI) Score	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.
Mean Change in Eczema Area and Severity Index EASI From Baseline to Day 28	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.
Percent Change in Eczema Area and Severity Index EASI From Baseline to Day 28	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.
Mean Change in Percent of Total Body Surface Area (%BSA) Affected	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.
Percent Change in Percent of Total Body Surface Area (%BSA) Affected	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.
Mean Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values	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 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. \[Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)\]
Percent Change in Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD) Values	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. Computation: Total Body Surface Area (BSA) x Validated Investigator Global Assessment in Atopic Dermatitis (vIGA-AD)
Mean Change in Average Weekly Peak Pruritus Numerical Rating Scale (PP-NRS) Score	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.
Proportion of Subjects With a Baseline Peak Pruritus Numerical Rating Scale (PP-NRS) Score ≥4 Who Achieved ≥4-point Reduction in PP-NRS Score	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.