Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK2831781 After an Intravenous (IV) Dose in Healthy Japanese and Caucasian Subjects, and a Subcutaneous (SC) Dose in Healthy Caucasian Subjects

This is a double-blind, placebo-controlled, randomized, parallel group, two-part study where single IV doses of GSK2831781 will be administered to healthy Japanese and Caucasian subjects in part A and SC doses will be administered to healthy Caucasian subjects in part B. GSK2831781 is a humanized, antibody-dependent cell cytotoxicity (ADCC) enhanced depleting monoclonal antibody that is specific to the lymphocyte activation gene-3 (LAG3) protein. LAG3 is a transmembrane receptor, which is upregulated on T cells following activation. The objective of the study is to assess the safety, tolerability, PK, PD and immunogenicity post administration of GSK2831781 in healthy subjects. The duration of the study is approximately 147 days for each subject enrolled. Approximately 36 subjects will be enrolled in the study, 16 subjects in Part A and 20 subjects in Part B.


Eligibility Criteria:
Inclusion Criteria:

* Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and 12-lead ECGs. A subject with a clinical abnormality or laboratory parameter(s) outside the reference range for the population being studied that is not specifically listed in the inclusion or exclusion criteria may be included if the Investigator (in consultation with the 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 or interpretation.
* Between 18 and 65 years of age inclusive, at the time of signing the informed consent.
* Body weight \>=40 kilogram (kg) and body mass index (BMI) \<=30 kilogram per meter square (kg/m\^2).
* Male.
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
* Japanese ancestry, defined as having been born in Japan, being descendants of four ethnic Japanese grandparents and two ethnic Japanese parents, holding a Japanese passport or identity papers, and being able to speak Japanese. Subjects should have lived outside Japan for less than 10 years at the time of screening.
* Caucasian ancestry, defined as Caucasian descent as evidenced by appearance and verbal confirmation of familial heritage (a subject has 2 Caucasian parents and 4 Caucasian grandparents).

Exclusion Criteria:

* History or presence of a disease that in the opinion of the investigator constitutes a risk when taking the study intervention or interfering with study assessment or interpretation of the data.
* A medical history of severe allergic reaction, angioedema, anaphylaxis, clinically significant drug hypersensitivity reaction, or autoimmune or immunodeficiency disorder.
* An active infection or a history of serious infections as follows:

  1. Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic agents) for an infection within 30 days before first dose. Topical treatments may be allowed at the Medical Monitor's discretion.
  2. A history of opportunistic infections.
  3. Recurrent or chronic infection, or other active infection, that in the opinion of the Investigator might cause this study to be detrimental to the subject.
  4. Symptomatic herpes zoster within 3 months prior to screening.
  5. History of tuberculosis (TB) (active or latent) irrespective of treatment status.
  6. A positive diagnostic TB test at screening (defined as a positive QuantiFERON test). In cases where the QuantiFERON test is indeterminate, the subject may have the test repeated once and if their second test is negative they will be eligible. In the event a second test is also indeterminate, the investigator has the option to undertake purified protein derivative (PPD) testing. If the PPD reaction is \<5 millimeter (mm) at 48 to 72 hours, then the subject is eligible. If the reaction is \>=5 mm, or PPD testing is not undertaken, the subject is not eligible.
* Any planned major surgical procedure during the study.
* A history of malignant neoplasm within the last 10 years, except for fully treated nonmetastatic basal or squamous cell cancers of the skin (within 3 years) that shows no evidence of recurrence.
* Use of prescription or non-prescription drugs (including recreational drugs and herbal medications) within 7 days or 5 half-lives (whichever is longer) prior to dosing, unless in the opinion of the investigator, the medication will not interfere with the study or compromise subject safety. Paracetamol (acetaminophen) at doses of \<=4 grams per day, and occasional use of non-steroidal anti-inflammatory drugs (NSAIDs) at licensed doses, are permitted.
* Received live vaccination within 4 weeks of Day 1, or plan to receive a live vaccination during the study until follow-up.
* Previous exposure to GSK2831781, or hypersensitivity to any excipients in the clinical formulation of GSK2831781.
* Treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
* Participation in a clinical trial and has received an investigational medicinal product (IMP) within the following time period prior to screening in the current study: 3 months, 5 half-lives, or twice the duration of the biological effect of the IMP (whichever is longer).
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
* Neutrophil or lymphocyte counts below the normal range.
* eGFR by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation \<=90 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2) at screening.
* ALT \>2x upper limit of normal (ULN) and bilirubin \>1.5x ULN (isolated bilirubin \>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at screening.
* Other clinically significant abnormalities of laboratory assessments, as judged by the Investigator and/or GSK Medical Monitor, that could affect the safety of the subject, or the interpretation of the data from the study.
* Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive hepatitis C antibody result at screening (Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid \[RNA\] test is obtained).
* Positive serology for human immunodeficiency virus (HIV) at screening.
* Positive pre-study drug/alcohol screen.
* QTc \>450 millisecond (msec), based on the mean of triplicate ECGs. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF; preferred method), or another method, machine or overread.
* History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units. One unit is equivalent to 8 grams (g) of alcohol: a halfpint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Unstable lifestyle factors, to the extent that in the opinion of the investigator they would interfere with the ability of a subject to complete the study.