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

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

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.

Study Overview

• Status: Completed
• Conditions: Plaque Psoriasis
• Intervention / Treatment: Drug: Tapinarof cream, 1%

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Encino, California, United States, 91436
      • Dermavant Investigational Site
  • Florida
    • Sanford, Florida, United States, 32771
      • Dermavant Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Dermavant Investigational Site
  • Texas
    • Austin, Texas, United States, 78759
      • Dermavant Investigational Site
    • San Antonio, Texas, United States, 78213
      • Dermavant Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Dermavant Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tapinarof (DMVT-505) cream, 1%; Tapinarof (DMVT-505) cream, 1% applied topically once daily	Drug: Tapinarof cream, 1%; Tapinarof cream, 1% applied topically once daily; Other Names: DMVT-505

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dermavant Sciences GmbH
• Investigators: Study Director: Michael McLaughlin, Dermavant Sciences, Inc.

Publications and helpful links

General Publications

• Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013 Feb;133(2):377-85. doi: 10.1038/jid.2012.339. Epub 2012 Sep 27.
• Bashaw ED, Tran DC, Shukla CG, Liu X. Maximal Usage Trial: An Overview of the Design of Systemic Bioavailability Trial for Topical Dermatological Products. Ther Innov Regul Sci. 2015 Jan;49(1):108-115. doi: 10.1177/2168479014539157. Epub 2014 Jun 27.
• Jett JE, McLaughlin M, Lee MS, Parish LC, DuBois J, Raoof TJ, Tabolt G, Wilson T, Somerville MC, DellaMaestra W, Piscitelli SC. Tapinarof Cream 1% for Extensive Plaque Psoriasis: A Maximal Use Trial on Safety, Tolerability, and Pharmacokinetics. Am J Clin Dermatol. 2022 Jan;23(1):83-91. doi: 10.1007/s40257-021-00641-4. Epub 2021 Oct 28.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): January 9, 2020
• Study Completion (Actual): January 9, 2020

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: DMVT-505-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No