Clinical trial NCT03956355: Tapinarof for the Treatment of Plaque Psoriasis in Adults (3001)
Official title: A Phase 3 Efficacy and Safety Study of Tapinarof for the Treatment of Plaque Psoriasis in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plaque Psoriasis
Keywords: Tapinarof
plaque psoriasis
adult
phase 3
topical
double-blind
efficacy
safety
psoriasis
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: IQVIA Biotech
First posted: 2019-05-20
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Following a 34-day screening period, eligible subjects will be randomized at a 2:1 ratio to receive once daily treatment with tapinarof cream, 1% or vehicle cream.
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, vehicle-controlled Phase 3 study to evaluate the efficacy and safety of topical tapinarof cream, 1% once daily for the treatment of plaque psoriasis in adults. Approximately 500 adult subjects with plaque psoriasis will be randomized 2:1 to receive either tapinarof cream, 1% or matching vehicle cream once daily for 12 weeks.

Detailed description: This study is a 12-week double-blind, vehicle-controlled treatment study in which subjects will be randomized to receive tapinarof cream, 1% or vehicle cream once daily for 12 weeks. At the end of the 12-week study treatment, qualified subjects completing the study will have the option to enter a separate open-label, long-term safety and efficacy study for an additional 40 weeks of treatment with tapinarof cream, 1%. Subjects who do not enroll in the open-label long-term study will complete a follow-up visit approximately 4 weeks after end of treatment in this study (at Week 16).

Eligibility criteria: Inclusion Criteria:

* Male and female subjects ages 18 to 75 years with clinical diagnosis of chronic plaque psoriasis and stable disease for at least 6 months prior to the study.
* BSA involvement ≥ 3% and ≤ 20%
* A PGA score of 2 (mild), 3 (moderate) or 4 (severe) at screening and baseline
* 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, including screening, during the treatment period, and for at least 4 weeks after the last exposure to study treatment
* Capable of giving written informed consent

Exclusion Criteria:

* Psoriasis other than plaque variant
* Any sign of infection of any of the psoriatic lesions
* Concurrent conditions or history of other diseases:
* Immunocompromised at Screening
* Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to the Baseline visit
* Acute active bacterial, fungal, or viral (herpes simplex, herpes zoster, chicken pox) skin infection within 1 week prior to the Baseline visit
* Significant dermatologic or inflammatory condition other than plaque psoriasis that, in the Investigator's opinion, would make it difficult to interpret data or assessments during the study
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5x the upper limit of normal (ULN)
* Total bilirubin \> 1.5 x ULN; total bilirubin \> ULN and ≤ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%
* Corrected QT interval \> 475
* Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result, or a positive anti-hepatitis B core antigen (anti-HBc) result
* 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
* Within a minimum of 5 half-lives for biologic agents:
* Within 4 weeks for systemic immunosuppressive or immunomodulating agents, fumaric acid derivatives, vitamin D3 and analogs, retinoids, psoralens, corticosteroids, adrenocorticotropic hormone analogs, and tazarotene
* 2 weeks for immunizations with a live viral component; drugs known to possibly worsen psoriasis, unless on a stable dose for \> 12 weeks
* With the exception of non-medicated emollients, 2 weeks for topical treatments including corticosteroids, immunomodulators, anthralin (dithranol), vitamin D derivatives or coal tar.
* Pregnant females or lactating females
* History of sensitivity to the study drugs, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates the subject's participation in the study
* 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
* Subjects with active infection that required oral, intramuscular, or intravenous administration of antibiotics, antifungal or antiviral agents within 7 days of Baseline/Day 1
* Previous known participation in a clinical study with tapinarof
* 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 interpretation of the results

Primary outcomes:
measure: Percent of Subjects Who Achieve a Physician Global Assessment (PGA) Score of Clear (0) or Almost Clear (1) With a Minimum 2-grade Improvement From Baseline at Week 12. Analyses Were Done Using Multiple Imputation
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Percent of Subjects With ≥ 75% Improvement in Psoriasis Area and Severity Index (PASI) From Baseline at Week 12. Analyses Were Done Using Multiple Imputation.
timeFrame: Baseline to Week 12
measure: Percent of Subjects With a PGA Score of 0 or 1 at Week 12. Analyses Were Done Using Multiple Imputation.
timeFrame: Baseline to Week 12
measure: Mean Change in Percent of Total Body Surface Area (%BSA) Affected From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Percent of Subjects With ≥90% Improvement in PASI Score From Baseline to Week 12. Analyses Were Done Using Multiple Imputation.
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Dermavant Investigative Site
state: Alabama
city: Phoenix
country: United States
facility: Dermavant Investigative Site
state: Arizona
city: Hot Springs
country: United States
facility: Dermavant Investigative Site
state: Arkansas
city: Rogers
country: United States
facility: Dermavant Investigative Site
state: Arkansas
city: Anaheim Hills
country: United States
facility: Dermavant Investigative Site
state: California
city: Fresno
country: United States
facility: Dermavant Investigative Site
state: California
city: Los Angeles
country: United States
facility: Dermavant Investigative Site
state: California
city: Northridge
country: United States
facility: Dermavant Investigative Site
state: California
city: San Diego
country: United States
facility: Dermavant Investigative Site
state: California
city: Santa Ana
country: United States
facility: Dermavant Investigative Site
state: California
city: Cromwell
country: United States
facility: Dermavant Investigative Site
state: Connecticut
city: Boca Raton
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Brandon
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Hialeah
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Miramar
country: United States
facility: Dermavant Investigative Site
state: Florida
city: Marietta
country: United States
facility: Dermavant Investigative Site
state: Georgia
city: Evansville
country: United States
facility: Dermavant Investigative Site
state: Indiana
city: Indianapolis
country: United States
facility: Dermavant Investigative Site
state: Indiana
city: New Albany
country: United States
facility: Dermavant Investigative Site
state: Indiana
city: Louisville
country: United States
facility: Dermavant Investigative Site
state: Kentucky
city: Owensboro
country: United States
facility: Dermavant Investigative Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Dermavant Investigative Site
state: Louisiana
city: New Orleans
country: United States
facility: Dermavant Investigative Site
state: Louisiana
city: New Orleans
country: United States
facility: Dermavant Investigative Site
state: Louisiana
city: Boston
country: United States
facility: Dermavant Investigative Site
state: Massachusetts
city: Clarkston
country: United States
facility: Dermavant Investigative Site
state: Michigan
city: Warren
country: United States
facility: Dermavant Investigative Site
state: Michigan
city: Saint Joseph
country: United States
facility: Dermavant Investigative Site
state: Missouri
city: Verona
country: United States
facility: Dermavant Investigative Site
state: New Jersey
city: Kew Gardens
country: United States
facility: Dermavant Investigative Site
state: New York
city: New York
country: United States
facility: Dermavant Investigative Site
state: New York
city: Rochester
country: United States
facility: Dermavant Investigative Site
state: New York
city: Cary
country: United States
facility: Dermavant Investigative Site
state: North Carolina
city: High Point
country: United States
facility: Dermavant Investigative Site
state: North Carolina
city: Norman
country: United States
facility: Dermavant Investigative Site
state: Oklahoma
city: Portland
country: United States
facility: Dermavant Investigative Site
state: Oregon
city: Pittsburgh
country: United States
facility: Dermavant Investigative Site
state: Pennsylvania
city: Johnston
country: United States
facility: Dermavant Investigative Site
state: Rhode Island
city: Arlington
country: United States
facility: Dermavant Investigative Site
state: Texas
city: College Station
country: United States
facility: Dermavant Investigative Site
state: Texas
city: Dripping Springs
country: United States
facility: Dermavant Investigative Site
state: Texas
city: Houston
country: United States
facility: Dermavant Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Dermavant Investigative Site
state: Texas
city: West Jordan
country: United States
facility: Dermavant Investigative Site
state: Utah
city: Saint Johns
country: Canada
facility: Dermavant Investigative Site
state: Newfoundland and Labrador
city: Ajax
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Coburg
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: North Bay
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Richmond Hill
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Waterloo
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Windsor
country: Canada
facility: Dermavant Investigative Site
state: Ontario
city: Montréal
country: Canada
facility: Dermavant Investigative Site
state: Quebec
Study officials:
affiliation: Dermavant Sciences GmbH
name: Victoria Butners
role: STUDY_DIRECTOR
References:
citation: Lebwohl MG, Stein Gold L, Strober B, Papp KA, Armstrong AW, Bagel J, Kircik L, Ehst B, Hong HC, Soung J, Fromowitz J, Guenthner S, Piscitelli SC, Rubenstein DS, Brown PM, Tallman AM, Bissonnette R. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. N Engl J Med. 2021 Dec 9;385(24):2219-2229. doi: 10.1056/NEJMoa2103629.