Safety, Tolerability, Pharmacokinetics and Target Engagement of GSK3858279 in Healthy Caucasian, Chinese and Japanese Participants

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), target engagement (TE) and immunogenicity of GSK3858279 when administered to healthy Caucasian, Chinese and Japanese participants.


Eligibility Criteria:
Inclusion Criteria:

* Participants between 20 and 65 years of age inclusive, at the time of signing the informed consent.
* Volunteers who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Participant 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.
* Participants who have evidence of completed vaccination for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an approved vaccine.
* Body weight within the range 45 - 100 killogram (kg) and body mass index (BMI) within the range 18-29.9 kg per meter square (/m2) (inclusive).
* Japanese participants are eligible based on meeting all of the following:
* Participants born in Japan
* Descendants of four ethnic Japanese grandparents and two ethnic Japanese parents.
* Have lived outside Japan for less than (\<) 10 years at the time of screening
* Chinese participants are eligible based on meeting all of the following
* Participants born in mainland China, Hong Kong or Taiwan
* Descendants of four Chinese grandparents and two Chinese parents
* Have lived outside China, Hong Kong or Taiwan for \<10 years at the time of screening
* Caucasian participants are eligible based on meeting the following
* Declaration of familial Caucasian/European ancestry (having 2 parents of Caucasian/European ancestry and 4 grandparents of Caucasian/European ancestry)
* Male or female participant
* Male participants are eligible to participate if they agree to the following for at least 28 weeks after the dose of study intervention: Refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR must agree to use contraception/barrier as detailed below: agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
* A female participant is eligible to participate if she is of non-reproductive potential.
* Capable of giving signed informed consent.

Exclusion Criteria:

* History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
* Personal or family history of cardiomyopathy.
* Abnormal blood pressure at screening as determined by the investigator.
* History of symptomatic herpes zoster.
* Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test.
* Significant allergies to humanized monoclonal antibodies as per principal investigator's and GSK medical monitor's judgements.
* History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
* History of lymphoma, leukaemia, or any malignancy within the last 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

ALT greater than (\>)1.5 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 percent \[%\]).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* Corrected QT (QTc) \>450 milliseconds (msec).
* History of Stevens Johnson Syndrome.
* Known immunodeficiency.
* Participants with a chronic infection (for example \[e.g.\], osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
* Previous or current history of bleeding diathesis, excessive bleeding or coagulation disorders.
* History of significant medical illness in the opinion of the investigator would interfere with the study procedures and / or assessments.
* Intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing until final follow-up visit.
* Live vaccine(s) or plans to receive such vaccines within 1 month of screening until final follow-up visit.
* Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
* Treatment with antiplatelet or anticoagulant agents within 7 days of dosing.
* Major surgery (as per investigator's judgement) within 3 months prior to dosing.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months.
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
* Current enrolment or past participation in any other clinical study involving an investigational drug intervention within the last 3 months or 5 half-lives (whichever is longer) of signing the ICF.
* Presence of Hepatitis B surface antigen (HBsAg) at screening.
* Presence of the Hepatitis B core antibody (HBcAb) at screening.
* Positive Hepatitis C antibody test result at screening.
* Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
* Abnormal clinically significant echocardiogram at screening, as assessed by the investigator.
* Cardiac troponin or N-terminal pro B-type natriuretic peptide (NT-proBNP) levels out of normal range at screening.
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Positive coronavirus disease 2019 (COVID-19): SARS-CoV2 polymerase chain reaction (PCR) or lateral flow test of a combined throat and nasopharyngeal swab or nasal swab only.
* Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \>14 units for males and \>14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Regular use of known drugs of abuse.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.