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
Condition: Healthy Volunteers
Intervention: GSK2831781; Placebo
Intervention description: GSK2831781 will be available as Dose-1 and Dose-2 as IV infusion or SC injection. Subjects will receive GSK2831781 Dose-1 IV diluted in 0.9% saline or GSK2831781 SC as multiples of Dose-2 SC.; Placebo will be 0.9% saline solution which will be administered in subjects as IV infusion or SC injection.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 36.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Japanese, Caucasian, pharmacokinetics, pharmacodynamics, GSK2831781, lymphocyte activation gene-3

Summary:

      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.