Clinical trial NCT04042103: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Plaque Psoriasis
Lead sponsor: Dermavant Sciences, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-01
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, single arm study
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants That Experienced Adverse Events (AEs), Severe Adverse Events, and Serious Adverse Events (SAEs)
timeFrame: Baseline to Week 4
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Biomarker Values, ECG Results or Vital Signs
timeFrame: Baseline to Week 4 or Follow-Up (7-10 days after Week 4 Visit)
measure: Number of Participants With Irritation as Assessed by the Local Tolerability Scale
timeFrame: Day 1, Day 15, Day 29
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: AUCo-tau
timeFrame: 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)
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Cmax
timeFrame: 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)
measure: Tapinarof and Tapinarof Sulfate (Metabolite) Plasma PK Parameters on Day 1 and Day 29: Tmax and t1/2
timeFrame: 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 outcomes:
measure: 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)
timeFrame: Baseline and Day 1
measure: Analysis of the Relationship Between Plasma Concentration and ΔQTcF
timeFrame: Day 1
measure: Mean Change From Baseline to Day 29 in Physician's Global Assessment (PGA)
timeFrame: Baseline to Day 29
measure: Mean Change From Baseline to Day 29 Psoriasis Area and Severity Index (PASI)
timeFrame: Baseline to Day 29
measure: Mean Change From Baseline to Day 29 in Percent of Total Body Surface Area (%BSA) Affected
timeFrame: Baseline to Day 29
Other outcomes:
Locations:
city: Encino
country: United States
facility: Dermavant Investigational Site
state: California
city: Sanford
country: United States
facility: Dermavant Investigational Site
state: Florida
city: Philadelphia
country: United States
facility: Dermavant Investigational Site
state: Pennsylvania
city: Austin
country: United States
facility: Dermavant Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Dermavant Investigational Site
state: Texas
city: Spokane
country: United States
facility: Dermavant Investigational Site
state: Washington
Study officials:
affiliation: Dermavant Sciences, Inc.
name: Michael McLaughlin
role: STUDY_DIRECTOR
References:
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.
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.
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.