Tapinarof for the Treatment of Plaque Psoriasis in Adults (3001)
Condition: Plaque Psoriasis
MeSH terms: Psoriasis
Intervention: Tapinarof; Vehicle Cream
Intervention description: Tapinarof cream, 1%, applied once daily; Vehicle cream applied once daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: The Investigator, study center staff, subject, and Sponsor will be blinded to treatment assignment.
Enrollment: 510.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Tapinarof; plaque psoriasis; adult; phase 3; topical; double-blind; efficacy; safety; psoriasis

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.
    

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