A Dose-Finding Study of GSK2894512 Cream in Subjects With Plaque Psoriasis

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 =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 =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 isotretinoi