Long Term Extension Study of Tapinarof Cream, 1% for Subjects With Atopic Dermatitis

Study Overview
=================
Brief Summary
-----------------
This is an open-label, long-term multicenter, study to evaluate the safety and efficacy of topical tapinarof cream, 1% in subjects with atopic dermatitis. Subjects in this study have completed treatment in one of two Phase 3 pivotal studies (DMVT-505-3101 or DMVT-505-3102) or completed treatment in the DMVT-505-2104 study, or directly enrolled into this study. This study will consist of up to 48 weeks of treatment and a 1 week safety follow-up period.

Detailed Description
-----------------
At the completion of the Week 8 visit of study DMVT-505-3101 or study DMVT-505-3102 or the Day 28 visit of study DMVT-505-2104, or Day 1 (Baseline) in this study, all eligible subjects will be offered enrollment in this open-label long-term extension (OL-LTE) study. Approximately 125 additional pediatric subjects ages 2 to < 18 years who are not eligible for participation in the Phase 3 pivotal studies (DMVT-505-3101 or DMVT-505-3102) will be enrolled directly into this OL-LTE study. Study visits during the treatment period for all subjects will occur every 4 weeks (± 3 days). The total duration of study participation will be approximately 49 weeks for rollover subjects (Baseline to Follow-up) and approximately 53 weeks for direct-enrolling subjects (Screening to Follow-up).

Official Title
-----------------
An Open-Label, Long-Term Extension Study to Evaluate the Safety and Efficacy of Tapinarof Cream, 1% in Subjects With Atopic Dermatitis

Conditions
-----------------
Atopic Dermatitis

Intervention / Treatment
-----------------
* Drug: Tapinarof cream, 1%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For Roll-over Subjects Only: Met the criteria as a Study Completer in one of three studies (DMVT-505-3101 study, DMVT-505-3102 study, or DMVT-505-2104 study). Must not be pregnant at Baseline For Direct-Enrolling Subjects Only: Male and female subjects ages 2 years to < 18 years at the time of consent with clinical diagnosis of AD Subjects with a vIGA-AD™ score of ≥ 3 and AD covering ≥ 40% of the BSA at Screening and Baseline (pre-randomization), or subjects with a vIGA-AD™ score of 2 at Screening and Baseline (pre-randomization) regardless of BSA. Subjects must have screened for the DMVT-505-3101 or DMVT-505-3102 study and failed to meet BSA and/or vIGA-AD™ eligibility criteria. AD present for at least 6 months for ages 6 years old and above or 3 months for ages 2 to 5 years old Must not be pregnant at Screening or Baseline For All Subjects: Female subjects of childbearing potential who are engaging in sexual activity that could lead to pregnancy should use acceptable birth control methods Subject, subject's parent, or legal representative must be capable of giving written informed consent/assent Exclusion Criteria: For Rollover Subjects Only: Subjects who were not receiving study drug at the time of the last visit in the pivotal study (DMVT-505-3101, DMVT-505-3102, or DMVT-505-2104) Used a prohibited concomitant product or procedure to treat AD during the pivotal study. Had an SAE that was related to treatment or experienced an AE that led to permanent discontinuation of treatment in the pivotal study. Pregnant females For Direct-Enrolling Subjects: 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
-----------------
Minimum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 1%, cream | Drug: Tapinarof cream, 1%<br>* Tapinarof cream, 1%, applied daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events and Serious Adverse Events | Incidence, Frequency, and duration of treatment emergent adverse events | Baseline to Week 49 | 
| Number of subjects with clinically significant laboratory test abnormalities |  | Baseline up to Week 49 | 
| Number of subjects with clinically significant vital signs abnormalities |  | Baseline up to Week 49 | 
| Mean Investigator- and Subject (or Caregiver)-assessed LTS scores by visit | 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 (0-4). Higher LTS scores represent more severe irritation. | Baseline up to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who experience vIGA-AD of clear (0) after treatment | 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. | Baseline up to Week 48 | 
| Proportion of subjects who experience vIGA-AD score of clear or almost clear (0 or 1) after treatment | 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 (0-4) morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Higher vIGA-AD scores represents more severe disease. | Baseline up to Week 48 | 
| Proportion of subjects who do not experience disease worsening (vIGA-AD ≥ 2) | 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 (0-4) morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, induration/papulation, lichenification, oozing/crusting. Higher vIGA-AD scores represents more severe disease. | Baseline up to Week 48 | 
| Absolute value, change and percent change from Baseline in %BSA affected by visit | The assessment of %BSA affected is an estimate of the percentage of total involved skin with AD. 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 AD will be evaluated (from 0% to 100%). %BSA is a static assessment made without reference to previous scores. | Baseline to each visit | 
| Absolute value, change and percent change from Baseline in Eczema Area and Severity Index (EASI) score by visit | The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. 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 each visit | 
| Proportion of subjects with ≥ 50%, 75%, and 90% improvement in EASI score from Baseline by visit | The EASI scoring system is a clinical tool that quantifies the severity of a subject's AD based on both lesion severity and %BSA affected. 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 each visit | 
| Mean change 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 each visit | 
| Proportion of subjects with a Baseline PP-NRS score ≥ 4 who achieve ≥ 4-point reduction in the PP-NRS from Baseline at each study visit | The PP-NRS is a scale 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 each visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pediatric, tapinarof, topical, eczema, phase 3