The decision not to progress the planned Phase 3 studies is a business decision based on the need to prioritise and focus resources within GSK.

This study will evaluate the efficacy and safety of GSK2894512 cream for the topical treatment of plaque psoriasis (psoriasis) with its vehicle cream. This is a randomized, double-blind, vehicle-controlled, parallel-group, multicenter study in adults with psoriasis. The aim of this study is to show superiority of GSK2894512 over vehicle by comparing their response rates. The study will consist of 3 periods: up to 4 weeks screening, 12 weeks blinded treatment, and 1 week post-treatment follow-up period. Subjects will apply randomized study treatment to all psoriasis lesions once daily for 12 weeks. Subjects will be stratified by Baseline physician global assessment (PGA) category (PGA score=2, PGA score >=3) at randomization. Approximately 120 subjects will be randomized into the study of which 80 will receive GSK2894512 1% cream and 40 will receive vehicle cream. Total duration of a subject's participation in the study will be approximately for 14 to 17 weeks.

Inclusion Criteria:

• Age >=18 years at the time of signing the informed consent.

• Clinical diagnosis of chronic stable plaque psoriasis. Diagnosis and chronicity to be confirmed and documented by an experienced dermatologist.

• Body surface area involvement >=2%.

• A PGA score of >=2.

• One target plaque located on the trunk or extremities that is at least 9 centimeter (cm)^2 in size with a target plaque severity score (TPSS) >=5 and an induration sub score >=2. Primary target plaque should not be located on the knees, elbows, feet, ankle, hands, intertriginous areas, face, or scalp.)

• Male or female. A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

  • Not a woman of childbearing potential (WOCBP), OR
  • Is a WOCBP who agrees to follow the specified contraceptive guidance throughout the study, including screening, during the treatment period, and for at least 1 week after the last exposure to study treatment.

• Capable of giving signed informed consent

Exclusion Criteria:

• Psoriasis other than plaque variant.

• Any sign of infection of any of the psoriatic lesions.

• Concurrent conditions and history of other diseases:

  • Immunocompromised (examples: lymphoma, acquired immunodeficiency syndrome) or have a history of malignant disease within 5 years before the Baseline visit.
  • Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks before the Baseline visit.
  • Active acute bacterial, fungal, or viral (examples: herpes simplex, herpes zoster, chicken pox) skin infection within 1 week before 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.

• 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 GSK2894512 or excipients of the study treatments, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation.

• Alanine transferase (ALT) >2 times upper limit of normal (ULN).

• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

• Stable chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C, examples: presence of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody test result at screening or within 3 months prior to starting study treatment) is acceptable if the subject otherwise meets entry criteria.

• QT interval corrected for heart rate according to Fridericia's formula QTcF >450 milliseconds (msec) or QTcF >480 msec in subjects with bundle branch block.

• Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation (examples: phototherapy, tanning beds/booths, or therapeutic sunbathing) within 4 weeks prior to the Baseline visit and/or intention to have such exposure during the study, which could potentially impact the subject's psoriasis (as determined by the investigator).

• Used any of the following treatments within the indicated period before the Baseline visit:

  • Minimum of 5 half-lives for biologic agents -12 months: rituximab or efalizumab; 8 months: ustekinumab; 5 months: secukinumab; 12 weeks: golimumab; 10 weeks: ixekizumab; 8 weeks: infliximab, adalimumab, or alefacept; 4 weeks: etanercept (list is not exclusive, contact medical monitor for questions).
  • 4 weeks -systemic treatments: cyclosporin, interferon, methotrexate, apremilast, tofacitinib, mycophenolate, thioguanine, hydroxyurea, sirolimus, azathioprine, other systemic immunosuppressive or immunomodulating agents, fumaric acid derivatives, vitamin D3 and analogs, retinoids (examples: acitretin, isotretinoin), psoralens, corticosteroids, or adrenocorticotropic hormone analogs.
  • 2 weeks -immunizations; drugs known to possibly worsen psoriasis, such as beta-blockers (example, propranolol), lithium, iodides, angiotensin-converting enzyme inhibitors, and indomethacin, unless on a stable dose for >12 weeks.
  • 2 weeks -topical treatments: corticosteroids, immunomodulators, anthralin (dithranol), Vitamin D derivatives (examples: calcipotriene, calcipotriol), retinoids (example, tazarotene), 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).

• Participated in a previous study using GSK2894512 or WBI-1001.

The investigator, study center staff, subject, and sponsor will be blinded to randomized study treatment assignments.