A First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Intravenous (IV) Dose of GSK2831781 in Healthy Volunteers and Patients With Plaque Psoriasis

Inclusion Criteria:

• Part A males aged between 18 and 65 years of age and Part B males and females aged between 18 and 75 years of age inclusive, at the time of signing the informed consent
• Part A: A body weight <=120 kilogram (kg) and Body mass index (BMI) within the range 19-32 kg/square meter (m^2) (inclusive), Part B: BMI within range 19-35 kg/m^2 (inclusive).
• Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent)
• Based on single or averaged Electrocardiogram QT interval corrected for heart rate (QTc) values of triplicate Electrocardiogram (ECGs) obtained over a brief recording period: Electrocardiogram QT interval corrected for heart rate using Fridericia's formula (QTcF) <450 milliseconds (msec)
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

For Part A study subjects only

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECGs. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Glaxosmithkline (GSK) Medical Monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures

Delayed type hypersensitivity (DTH) cohorts only

• Subjects with a history of Bacillus Calmette Guérin (BCG) vaccination as evidence by either: A BCG scar and verbal confirmation of BCG vaccination ; Or documented medical history of a BCG vaccination with or without a BCG scar
• Subjects with a history of current vaccination for Tetanus, diphtheria, measles, pertussis, mumps and rubella

For Part B study subjects only

• Subject has psoriasis covering Body Surface Area (BSA) >=3 percent as assessed at Screening and Day-1
• Subject has had a confirmed diagnosis of chronic plaque-type psoriasis (without recent documented flare within 30 days prior to screening) for at least 6 months
• Subject has at least 2 stable plaques assessed at Screening and Day -1. One of a suitable size and in a site suitable for repeat biopsy, and one for index lesion Plaque Lesional Severity Score (PLSS) scoring. Both must have a PLSS lesional score of >=2 for the induration component (moderate or above), >=1 for erythema and scaling with a total score of >=5. The biopsy lesion must not be on the face, groin or scalp and must be protected from the sun
• A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screening and negative urine hCG test at Day -1 for Females of Reproductive Potential [FRP]), not lactating, and at least one of the given conditions applies: Non-reproductive potential defined as pre-menopausal females with a documented tubal ligation; or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; or hysterectomy; or documented bilateral oophorectomy.

Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be 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 use a barrier method (male condom or female diaphragm) plus to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP from 28 days prior to the first dose of study medication and until completion of the follow-up visit.

The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. The investigator or designee should remind the subjects of the need to comply with these requirements approximately monthly, either at study visits or by telephone call until the follow-up visit.

Exclusion Criteria:

• Received live vaccine (s) attenuated or recombinant within 4 weeks of Day 1 or plan to receive a live vaccination during the study until follow-up
• Subjects from a high risk area of the world for tuberculosis or have history of tuberculosis or have close family members with confirmed Mycobacterium tuberculosis (MTB) infection or positive at screening by Quantiferon testing
• Subject is unable to abstain from travelling to areas with high endemic rates of infectious diseases until the end of the follow up period
• A medical history of severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency
• Subjects with neutrophil results below the normal range at screening and baseline
• Subjects with any clinical, even mild, Gastrointestinal (GI) upset such as, but not limited to, diarrhea or abdominal cramping during the previous week before dosing, as well as history of more chronic GI upset, e.g. Irritable Bowel Syndrome (IBS)
• Current evidence of ongoing or acute infection within 3 months prior to the first dose of study drug, such as: Serious local infection (e.g. cellulitis, abscess); Systemic infection [e.g. pneumonia, septicaemia, Tuberculosis (TB)]
• Subjects who test positive for pre-existing ADA to GSK2831781 at screening.
• History of malignancy, except for basal cell or squamous cell carcinoma, or in situ cervical carcinoma that has been fully treated and shows no evidence of recurrence
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
• History of sensitivity to any of the study medications or Tuberculin Purified Protein Derivative (PPD) challenge agent, or components thereof or a history of drug (or Immunoglobulin G therapeutic antibodies) or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive pre-study drug/alcohol screen
• A positive test for Human Immunodeficiency Virus (HIV) antibody
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day
• Subjects with an aspartate aminotransferase and/or gamma glutamyltransferase level above the upper limit of normal at screening and/or baseline will be excluded

For Part A study subjects only

• Use of prescription drugs or non-prescription drugs, if in the opinion of the investigator (in consultation with the GSK medical monitor), the medication will interfere with the study procedures or compromise subject safety
• Subjects must not currently be taking any of the following: topical steroids on the arms, oral or systemic steroids or any other immune-modulators (the washout period will be determined, on a case by case basis, by the investigator in consultation with the GSK medical monitor)
• Subjects with an aspartate aminotransferase and/or gamma glutamyltransferase level above the upper limit of normal at screening and/or baseline will be excluded.

For Part A (only cohorts with DTH challenge) study subjects only:

• Use of nicotine patches on the arm at screening that would interfere with the injection sites
• Presence of tattoos, naevi or other skin abnormalities such as keloids (or a history of keloids) that may, in the opinion of the investigator, interfere with DTH assessments
• Subjects participating, within seven days of screening, in recreational sun-bathing, or the use of a sun-bed, on the area of the skin from the wrist to the shoulder (inclusive)

For Part B study subjects only:

• History of significant cardiac, endocrinologic, haematologic, pulmonary, metabolic, renal, hepatic, immunologic (excluding psoriasis and psoriatic arthritis), urologic, neurologic, dermatologic (except psoriasis), psychiatric or gastrointestinal conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at unacceptable risk
• Clinically significant abnormalities of laboratory assessments (not related to disease) as judged by the investigator and/or GSK medical monitor
• All systemic psoriasis medications, including psoralen long-wave ultraviolet radiation treatments, or other systemic immunosuppressives, are not allowed within 5 half lives prior to Day-1 (Methotrexate and cyclosporin are not allowed within 8 weeks of Day -1; Psoralen long-wave Ultraviolet (UV) is not allowed within 4 weeks of Day-1). Subjects should not be included if the investigator considers that the subject is at high risk of requiring rescue with prohibited medication for duration of study up to follow-up. This assessment should be based on current disease activity or a history of frequent and/or severe flares requiring systemic immunosuppression.
• The use of single treatment phototherapy (ultraviolet B or self treatment with tanning beds) is not allowed within 14 days prior to Day -1
• The use of topical therapies for psoriasis are not allowed with 7 days prior to Day-1 on the index lesion or biopsy plaque
• Previous treatment with anti- Tumour necrosis factor (TNF)/ Interleukin (IL)-12/IL-23 or any other monoclonal antibodies is not allowed within 12 weeks prior to Day-1
• Patients that require narrow therapeutic index medications from Screening to Follow-up
• Vulnerable subjects (e.g. person kept in detention)
• Subjects who are not able to understand and communicate in the native language of the country where the study is conducted.
• Subjects who work for the Sponsor or CRO.