Maximal Use Study of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis

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 adults with plaque psoriasis.

Official Title
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Open-Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis

Conditions
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Plaque Psoriasis

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 18 to 75 with a confirmed clinical diagnosis of plaque psoriasis and stable disease for at least 6 months prior to the study BSA involvement ≥ 20% PGA score of ≥ 3 at screening Females of child bearing potential and male subjects 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 Exclusion Criteria: Psoriasis other than plaque variant Any sign of infection of any of the psoriatic lesions Evidence of significant hepatic, renal, respiratory, endocrine, hematologic, neurologic, psychiatric, or cardiovascular (CV) system abnormalities or laboratory abnormality that will affect the health of the subject or interfere with the interpretation of the results Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation within 4 weeks prior to the Baseline visit and/or plans to have such exposures during the study which could potentially impact the subject's psoriasis Use of any prohibited medication within the indicated period before the first dose of study drug Pregnant females or lactating females The subject has received an investigational product within 30 days, 5 half-lives, or twice the duration of the biological effect of the study drug (whichever is longer) prior to first dose of study drug Current or a history of cancer within 5 years except for fully excised skin basal cell carcinoma, squamous cell carcinoma or carcinoma in situ of the cervix Previous known participation in a clinical study with tapinarof

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Open-label, single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapinarof (DMVT-505) cream, 1%<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), Severe Adverse Events, and Serious Adverse Events (SAEs) | Frequency and severity of AEs (local and systemic) | Baseline to Week 4 | 
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Biomarker Values, ECG Results or Vital Signs | Changes in laboratory values, biomarker values, ECG results and vital signs were assessed for clinical relevance. | Baseline to Week 4 or Follow-Up (7-10 days after Week 4 Visit) | 
| Number of Participants With Irritation as Assessed by the Local Tolerability Scale | At each specified study visit, the Investigator (or qualified evaluator) assessed the presence and overall degree of irritation at the application sites, according to the LTS. The score will ideally represent an 'average' across all application sites. To the fullest extent possible, the same Investigator (or designated evaluator) will perform all tolerability assessments for an individual participant throughout the study. | Day 1, Day 15, Day 29 | 
| Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: AUCo-tau | The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug. | Day 1 and Day 29 (PK samples collected at pre-dose and at 1, 2, 3, 4, 5, 8, 12, and 24 hours after dosing) | 
| Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Cmax | The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing. | Day 1 and Day 29 (PK samples collected at pre-dose and at 1, 2, 3, 4, 5, 8, 12, and 24 hours after dosing) | 
| Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Tmax and t1/2 | 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 29 (PK samples collected at pre-dose and at 1, 2, 3, 4, 5, 8, 12, and 24 hours after dosing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in QTcF (ΔQTcF) at Each Post-treatment Time Point on the Sampling Day With the Higher Cmax (Day 1 or Day 29) | Identify clinically relevant effect of tapinarof on cardiac conduction | Baseline and Day 1 | 
| Analysis of the Relationship Between Plasma Concentration and ΔQTcF | The relationship between tapinarof plasma concentrations and ∆QTcF was investigated using a linear mixed-effects modeling approach with ΔQTcF as the dependent variable. A linear model with an intercept was fitted for tapinarof plasma concentrations, which represented the data in an acceptable way. The slope of tapinarof plasma concentration in the concentration-QTc relationship was estimated. | Day 1 | 
| Mean Change From Baseline to Day 29 in Physician's Global Assessment (PGA) | The PGA is a clinical tool for assessing the current state/severity of a subject's psoriasis 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, scaling, and plaque thickness/elevation as guidelines. Higher PGA scores represent more severe disease. This scale ranges from 0 to 5, with 0 = best outcome. | Baseline to Day 29 | 
| Mean Change From Baseline to Day 29 Psoriasis Area and Severity Index (PASI) | The Psoriasis Area and Severity Index (PASI) scoring system combines the assessment of lesion severity and extent of affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, and legs). Each area is assessed for 3 signs: erythema (redness), induration (plaque thickness), and scale. The severity of each sign in each body area is assessed and scored independently using a 5-point scale, where 0=none, 1=slight, 2=mild, 3=moderate, 4=severe. Each area is also assessed for percent of skin involved: 0 = (0%), 1 = (1-<10%), 2 = (10-<30%), 3 = (30-<50%), 4 = (50 -<70%), 5 = (70-<90%), 6 = (90-100%). The individual scores are multiplied by a weighted factor for each body region; the sum of these scores gives the overall PASI score. Higher scores indicate more severe disease. PASI is a static assessment made without reference to previous scores. | Baseline to Day 29 | 
| Mean Change From Baseline to Day 29 in Percent of Total Body Surface Area (%BSA) Affected | 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 29 |