Back to resultsMaximal Use Study of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis
Primary Purpose
Plaque Psoriasis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tapinarof cream, 1%
Sponsored by
About this trial
This is an interventional treatment trial for Plaque Psoriasis
Eligibility 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
Sites / Locations
- Dermavant Investigational Site
- Dermavant Investigational Site
- Dermavant Investigational Site
- Dermavant Investigational Site
- Dermavant Investigational Site
- Dermavant Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tapinarof (DMVT-505) cream, 1%
Arm Description
Tapinarof (DMVT-505) cream, 1% applied topically once daily
Outcomes
Primary Outcome Measures
Number of Participants That Experienced Adverse Events (AEs), Severe Adverse Events, and Serious Adverse Events (SAEs)
Frequency and severity of AEs (local and systemic)
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.
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.
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.
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.
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.
Secondary Outcome Measures
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
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04042103
Brief Title
Maximal Use Study of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis
Official Title
Open-Label Maximal Use Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
July 23, 2019 (Actual)
Primary Completion Date
January 9, 2020 (Actual)
Study Completion Date
January 9, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dermavant Sciences GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plaque Psoriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, single arm study
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tapinarof (DMVT-505) cream, 1%
Arm Type
Experimental
Arm Description
Tapinarof (DMVT-505) cream, 1% applied topically once daily
Intervention Type
Drug
Intervention Name(s)
Tapinarof cream, 1%
Other Intervention Name(s)
DMVT-505
Intervention Description
Tapinarof cream, 1% applied topically once daily
Primary Outcome Measure Information:
Title
Number of Participants That Experienced Adverse Events (AEs), Severe Adverse Events, and Serious Adverse Events (SAEs)
Description
Frequency and severity of AEs (local and systemic)
Time Frame
Baseline to Week 4
Title
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Biomarker Values, ECG Results or Vital Signs
Description
Changes in laboratory values, biomarker values, ECG results and vital signs were assessed for clinical relevance.
Time Frame
Baseline to Week 4 or Follow-Up (7-10 days after Week 4 Visit)
Title
Number of Participants With Irritation as Assessed by the Local Tolerability Scale
Description
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.
Time Frame
Day 1, Day 15, Day 29
Title
Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: AUCo-tau
Description
The AUC in plasma is a pharmacokinetic parameter that describes the overall exposure of the drug.
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)
Title
Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Cmax
Description
The Cmax is a pharmacokinetic parameter that describes the highest concentration of the drug that is achieved after dosing.
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)
Title
Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Tmax and t1/2
Description
The tmax is a pharmacokinetic parameter that describes the time point at which the highest concentration of the drug is achieved after dosing.
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)
Secondary Outcome Measure Information:
Title
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)
Description
Identify clinically relevant effect of tapinarof on cardiac conduction
Time Frame
Baseline and Day 1
Title
Analysis of the Relationship Between Plasma Concentration and ΔQTcF
Description
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.
Time Frame
Day 1
Title
Mean Change From Baseline to Day 29 in Physician's Global Assessment (PGA)
Description
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.
Time Frame
Baseline to Day 29
Title
Mean Change From Baseline to Day 29 Psoriasis Area and Severity Index (PASI)
Description
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.
Time Frame
Baseline to Day 29
Title
Mean Change From Baseline to Day 29 in Percent of Total Body Surface Area (%BSA) Affected
Description
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.
Time Frame
Baseline to Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael McLaughlin
Organizational Affiliation
Dermavant Sciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Dermavant Investigational Site
City
Encino
State/Province
California
ZIP/Postal Code
91436
Country
United States
Facility Name
Dermavant Investigational Site
City
Sanford
State/Province
Florida
ZIP/Postal Code
32771
Country
United States
Facility Name
Dermavant Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19103
Country
United States
Facility Name
Dermavant Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78759
Country
United States
Facility Name
Dermavant Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78213
Country
United States
Facility Name
Dermavant Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26634191
Citation
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.
Results Reference
background
PubMed Identifier
23014338
Citation
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.
Results Reference
background
PubMed Identifier
34713415
Citation
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.
Results Reference
derived
Learn more about this trial
Maximal Use Study of Tapinarof Cream, 1% in Adults With Extensive Plaque Psoriasis
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