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

• ClinicalTrials.gov Identifier: NCT04042103
• Recruitment Status: Completed
• First Posted: August 1, 2019
• Results First Posted: May 6, 2022
• Last Update Posted: May 6, 2022
• Sponsor: Dermavant Sciences GmbH
• Information provided by (Responsible Party): Dermavant Sciences, Inc. ( Dermavant Sciences GmbH )

Study Description

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 adults with plaque psoriasis.

Condition or disease	Intervention/treatment	Phase
Plaque Psoriasis	Drug: Tapinarof cream, 1%	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-label, single arm study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis
• Actual Study Start Date: July 23, 2019
• Actual Primary Completion Date: January 9, 2020
• Actual Study Completion Date: January 9, 2020

Arms and Interventions

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 Name: DMVT-505

Outcome Measures

Primary Outcome Measures :

1. Number of Participants That Experienced Adverse Events (AEs), Severe Adverse Events, and Serious Adverse Events (SAEs) [ Time Frame: Baseline to Week 4 ]
   Frequency and severity of AEs (local and systemic)
2. Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Biomarker Values, ECG Results or Vital Signs [ Time Frame: Baseline to Week 4 or Follow-Up (7-10 days after Week 4 Visit) ]
   Changes in laboratory values, biomarker values, ECG results and vital signs were assessed for clinical relevance.
3. Number of Participants With Irritation as Assessed by the Local Tolerability Scale [ Time Frame: Day 1, Day 15, Day 29 ]
   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.
4. Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: AUCo-tau [ Time Frame: 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) ]
   The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.
5. Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Cmax [ Time Frame: 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) ]
   The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.
6. Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Tmax and t1/2 [ Time Frame: 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) ]
   The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.

Secondary Outcome Measures :

1. 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) [ Time Frame: Baseline and Day 1 ]
   Identify clinically relevant effect of tapinarof on cardiac conduction
2. Analysis of the Relationship Between Plasma Concentration and ΔQTcF [ Time Frame: Day 1 ]
   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.
3. Mean Change From Baseline to Day 29 in Physician's Global Assessment (PGA) [ Time Frame: Baseline to Day 29 ]
   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.
4. Mean Change From Baseline to Day 29 Psoriasis Area and Severity Index (PASI) [ Time Frame: Baseline to Day 29 ]
   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.
5. Mean Change From Baseline to Day 29 in Percent of Total Body Surface Area (%BSA) Affected [ Time Frame: Baseline to Day 29 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Dermavant Investigational Site

Encino, California, United States, 91436

United States, Florida

Dermavant Investigational Site

Sanford, Florida, United States, 32771

United States, Pennsylvania

Dermavant Investigational Site

Philadelphia, Pennsylvania, United States, 19103

United States, Texas

Dermavant Investigational Site

Austin, Texas, United States, 78759

Dermavant Investigational Site

San Antonio, Texas, United States, 78213

United States, Washington

Dermavant Investigational Site

Spokane, Washington, United States, 99202

Sponsors and Collaborators

Dermavant Sciences GmbH

Investigators

• Study Director: Michael McLaughlin; Dermavant Sciences, Inc.

  Study Documents (Full-Text)

Documents provided by Dermavant Sciences, Inc. ( Dermavant Sciences GmbH ):

Study Protocol  [PDF] April 26, 2019

Statistical Analysis Plan  [PDF] February 6, 2020

More Information

Publications:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Dermavant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT04042103
• Other Study ID Numbers: DMVT-505-2002
• First Posted: August 1, 2019
• Results First Posted: May 6, 2022
• Last Update Posted: May 6, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases