A Dose-Finding Study of GSK2894512 Cream in Subjects With Plaque Psoriasis
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: GSK2894512 1% Cream; GSK2894512 0.5% Cream; Vehicle cream
Intervention description: 1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically; 0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically; White to off-white vehicle cream base to be applied topically
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 227.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Double blind; Dose-finding; Vehicle-Controlled; GSK2894512; Plaque Psoriasis

Summary:

      This study will evaluate the efficacy and safety of two concentrations (0.5 percent [%] and
      1%) and two application frequencies (once a day and twice a day) of GSK2894512 cream for the
      topical treatment in subjects with plaque psoriasis. Results from this study will be
      considered when selecting the most appropriate concentration of GSK2894512 cream and dosing
      frequency in future clinical safety and efficacy studies. This is a multicenter (United
      States, Canada, and Japan), randomized, double-blind (sponsor-unblind), vehicle-controlled,
      6-arm, parallel-group, dose-finding study. Two concentrations of GSK2894512 cream (0.5% and
      1%) and a vehicle control cream will be equally randomized and evaluated following
      application to all psoriasis lesions (except on the scalp) once daily (evening) or twice
      daily (morning and evening) for 12 weeks. This study will consist of 3 periods: up to 4 weeks
      screening, 12 weeks double-blind treatment, and 4 weeks post-treatment follow-up. The total
      duration of subject participation will be approximately 16 to 20 weeks. Approximately 270
      adult males and females subjects with plaque psoriasis will be screened in order to have at
      least 228 randomized subjects (38 subjects for each of the 6 treatment groups) and
      approximately 204 evaluable subjects overall. Approximately 30 subjects will be randomized in
      Japan to achieve at least 24 evaluable Japanese subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between 18 to 65 years of age inclusive, at the time of signing the
             informed consent.

          -  Confirmed clinical diagnosis of chronic stable plaque psoriasis for >=6 months.

          -  Body surface area involvement >=1% and <=15%, excluding scalp, at Screening and
             Baseline.

          -  A PGA of psoriasis score >=2 at Baseline.

          -  One target plaque located on the trunk or proximal parts of extremities (excluding
             knees, elbows, and intertriginous areas) that is at least 3 (centimetre) cm х 3 cm in
             size at Screening and Baseline with a severity representative of the subject's overall
             disease.

          -  A female subject is eligible to participate if she is not pregnant (as confirmed by a
             negative urine human chorionic gonadotrophin test), not lactating, and at least one of
             the following conditions applies: Non-reproductive potential defined as: 1)
             Pre-menopausal females with one of the following procedures documented: tubal
             ligation; hysteroscopic tubal occlusion procedure with follow-up confirmation of
             bilateral tubal occlusion; hysterectomy; bilateral oophorectomy. 2) Post-menopausal
             defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample
             with simultaneous follicle stimulating hormone and estradiol levels consistent with
             menopause and falling into the central laboratory's postmenopausal reference range is
             confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal
             status is in doubt are required to use one of the highly effective contraception
             methods if they wish to continue their HRT during the study. Otherwise, they must
             discontinue HRT to allow confirmation of post-menopausal status prior to study
             enrolment; Reproductive potential and agrees to follow one of the options listed in
             the modified list of highly effective methods for avoiding pregnancy in females of
             reproductive potential from 30 days prior to the first dose of study medication and
             until (at least five terminal half-lives OR until any continuing pharmacologic effect
             has ended, whichever is longer) after the last dose of study medication and completion
             of the follow-up visit.

        Exclusion Criteria:

          -  Any sign of infection of any of the psoriatic lesions.

          -  A history or ongoing serious illness or medical, physical, or psychiatric condition(s)
             that, in the investigator's opinion, may interfere with the subject's completion of
             the study.

          -  Known hypersensitivity to the study treatment excipients, or a history of drug or
             other allergy that, in the opinion of the investigator, contraindicates participation.

          -  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, or positive hepatitis C antibody test result within 3
             months of screening.

          -  Liver function tests: alanine aminotransferase >=2x upper limit of normal (ULN);
             alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable
             if bilirubin is fractionated and direct bilirubin <35%).

          -  QTc >=450 milliseconds (msec) or QTc >=480 msec for subjects with bundle branch block.

        NOTES: The QTc is the QT interval corrected for heart rate according to Fridericia's
        formula (QTcF), with machine over-read. The QTc should be based on a single ECG obtained
        over a brief recording period. If QTc is outside of the threshold value, triplicate ECGs
        may be performed with the QTc values averaged.

          -  Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources
             of UV radiation (eg, sunlight or tanning booth) within 4 weeks prior to the baseline
             visit and/or intention to have such exposure during the study, which is thought by the
             investigator to potentially impact the subject's psoriasis.

          -  Used any of the following treatments within the indicated washout period before the
             baseline visit: 1) 12 weeks or 5 half-lives (whichever is longer) - biologic agents
             (eg, 24 weeks for alefacept, 12 weeks for etanercept, 15 weeks for ustekinumab); 2) 12
             weeks - oral retinoids (eg, acitretin or isotretinoin); 3) 8 weeks - cyclosporin,
             interferon, methotrexate, other systemic immunosuppressive or immunomodulating agents,
             or psoralen plus UVA light treatment; 4) 4 weeks - systemic corticosteroids or
             adrenocorticotropic hormone analogs; 5) 2 weeks - immunizations; drugs known to
             possibly worsen psoriasis, such as beta-blockers (eg, propranolol), lithium, iodides,
             angiotensin-converting enzyme inhibitors, and indomethacin, unless on a stable dose
             for >12 weeks; 6) 2 weeks - topical treatments: corticosteroids, immunomodulators,
             anthralin (dithranol), Vitamin D derivatives, retinoids, or coal tar (used on the
             body).

          -  Participated in a clinical study and received an investigational product within the
             following time period prior to the baseline visit: 4 weeks, 5 half-lives, or twice the
             duration of the biological effect of the investigational product (whichever is
             longer).

          -  History of alcohol or other substance abuse within the last 2 years.

          -  Participated in a previous study using GSK2894512 (or WBI-1001).