A First-time in Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics and Target Engagement of GSK4528287 in Healthy Participants

Inclusion criteria

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
• White blood cell greater than or equal to (>=) lower limit of normal (LLN), including both lymphocyte counts >= LLN and neutrophil counts >= LLN, at both screening and pre-dose (Day-1) Note: in cases where the test is abnormal, the participant may have the test repeated once and if their second test is normal, they will be eligible. In the event a second test is also abnormal, the participant is not eligible
• Electrocardiogram (ECG) with no clinically significant abnormality at the discretion of the investigator/designee
• Participants with a confirmed positive vaccination status for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines as per local/site guidance
• SARS-CoV-2 screening test negative as per local guidance
• If dosing is during influenza season (October to April per local guidelines), participants who have not had a seasonal influenza vaccine must receive a medicines and healthcare products regualtory agency (MHRA)-approved influenza vaccine at least 30 days before dosing
• Body weight >= 50 kilograms (kg) and body mass index (BMI) within the range 18-32 kilograms per square meters (kg/m^2) (inclusive)
• Male and/or female of non-childbearing potential
• Male participants are eligible to participate if they agree to the following during the study intervention period and for 48 weeks after the single dose of study intervention: refrain from donating sperm; 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 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 (WOCBP) who is not currently pregnant
• A female participant is eligible to participate if she is a woman of non-childbearing potential (WONCBP)
• Capable of giving signed informed consent

Exclusion criteria

• History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, 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
• Abnormal blood pressure as determined by the investigator
• Symptomatic herpes zoster within 3 months prior to screening
• Prior medical history of anaphylaxis or severe adverse reactions to vaccines
• Significant allergies to humanized monoclonal antibodies
• 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)
• Immunodeficiency or autoimmunity assessed by medical history.
• A history of recurrent infections
• Treatment of any significant infection within 3 months prior to the first dose of study drug, including both serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, shingles)
• Any history of chronic infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
• Any acute infection (including upper respriatory tract infection [URTI] and urinary tract infection [UTI]) which has not fully resolved within four weeks of dosing
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) medical monitor, poses a safety risk with regards to participation in the trial
• History of malignancy, including malignant or non-malignant skin cancer
• Prior moderate/severe SARS-CoV-2 infection requiring oxygen supplementation or admission to hospital
• Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing
• Antibiotics or antiviral therapy within 30 days of dosing
• Receipt of live vaccination within 1 month prior to screening or plan to receive live vaccination during the study
• Past or intended use of over the counter or prescription medication including herbal medications within 7 days prior to dosing
• The participant has participated in a clinical trial and has received an investigational product (IP) within the following time-period prior to the first dosing day of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
• Exposure to more than 4 new chemical entities within 12 months prior to dosing
• Current enrolment or past participation in this clinical study.
• Participation in a clinical study that would result in donation of blood or blood products in excess of 500 millilitres (mL) within a 56 day period
• A positive diagnostic Mycobacterium tuberculosis bacteria (MTB) test at screening (defined as positive QuantiFERON Gold test)
• Positive test for HIV antibody at screening
• Positive drug/alcohol test, including tetrahydrocannabinol, at screening or Day 1
• Positive smoke breath analyzer levels indicative of smoking history at screening and in house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g., nicotine patches, vaporizing devices) within 6 months prior to screening
• A positive confirmation of SARS CoV 2 infection or signs and symptoms suggestive of SARS CoV 2 at screening or pre dose
• The participant is at high risk of MTB infection in the opinion of the Investigator. Risk factors include residing in a high prevalence area or having close contact with a person with confirmed MTB infection
• The participant has a phobia to needles
• Regular alcohol consumption within 6 months prior to study, defined as: An average weekly intake of greater than (>)14 units of alcohol. One unit is equivalent to 8 grams (g) of alcohol: a half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 measure (25 mL) of spirits
• Regular use of known drugs of abuse, including tetrahydrocannabinol
• Alanine aminotransferase (ALT or AST) >1.0*upper limit of normal (ULN)
• Total bilirubin >1.0*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is less than or equal to (<=) 1.5*ULN
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) at screening or Day -1 or within 3 months prior to first dose of study intervention.
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
• Positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
• QTcF (QT interval corrected for heart rate according to Fredericia's formula) >450 milliseconds (msec).