This study was terminated due to meeting protocol defined futility.

This study will evaluate the mechanistic basis for the analgesic effects of GSK3858279 in humans by using a battery of experimental pain assessments in healthy participants. This will be placebo-controlled, three-period two-treatment crossover study. In each period, participants will receive either GSK3858279 or placebo in a 1:1 ratio. Only healthy male participants will be enrolled into the study. The duration of the study will be approximately 6 months.

Inclusion Criteria:

• Participants must be 18 to 50 years of age inclusive, at the time of signing the informed consent.

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.

• Participants with body weight within 50-100 kg and body mass index (BMI) within the range 18 to 30 kg per meter square (kg/m^2) (inclusive).

• Must be male participants: Participants must agree to the following during the intervention period and for at least 90 days after the last dose of study intervention:

  1. Refrain from donating sperm plus, either
  2. 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
  3. Must agree to use contraception/barrier as detailed below:

  (i) Agree to use a male condom. (ii) 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.

• 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.

Exclusion Criteria:

• Participants with history or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, 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 as determined by the investigator.
• Symptomatic herpes zoster within 3 months prior to screening.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: a positive (not indeterminate) QuantiFERON-TB Gold test.
• 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).
• Lymphoma, leukemia, or any malignancy. Those who are at risk of deoxyribonucleic acid (DNA) repair diseases or any family history of DNA repair disease.
• Alanine transaminase (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 less than [<]35%).
• 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 interval (QTc) >450 msec.
• History of Stevens-Johnson syndrome.
• Known immunodeficiency.
• Participants with an acute, recurrent or chronic infection (for example, osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
• Previous or current history of excessive bleeding or coagulation disorders.
• Previous history of hypertrophic or keloid scarring.
• Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud's disease, urticaria, and hypothyroidism) or pain (such as disease that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia, neuropathy).
• Participants indicating pain tests intolerable at screening. Participants achieving tolerance at >80% of maximum input intensity for cold pressor and electrical pain tests are to be excluded. If pressure pain test tolerance is >80% of maximum input intensity they may be enrolled as per Principal Investigator (PI) judgement.
• History or presence of post-inflammatory hyperpigmentation. Applicable for the participants in the UVB-Modified Intent-To-Treat (MITT) population only.
• Participants with Fitzpatrick skin type IV, V or VI. Applicable for the participants in the UVB-MITT population only.
• Any of the following on the proposed test area on the back: widespread acne, freckles, tattoos, birthmarks or scarring (investigator discretion may be used to determine if small areas may be avoided in the testing area on the back). Applicable for the participants in the UVB-MITT population only.
• A minimal erythema dose (MED) higher than 355 millijoule per square centimeter (mJ/cm^2) at screening. Applicable for the participants in the UVB-MITT population only.
• Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to screening until after follow-up visit.
• Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
• Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) or immunosuppressants within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Treatment with anti-platelet or anti-coagulant agents within 7 days of dosing.
• Major surgery (as per investigator's judgement) within 3 months prior to dosing.
• Participant has made a blood or plasma donation or has had a comparable blood loss (>450 milliliters [mL]) within the last 3 months prior to the Screening Visit. Blood donation during the study is not permitted.
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
• Current enrollment or past participation in any other clinical study involving an investigational study intervention within the last 3 months, 5-half-lives or twice the duration of the biological product before screening in this current study.
• Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention.
• Presence of Hepatitis B core antibody (HbcAb) at screening 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.
• Abnormal clinically significant echocardiogram at screening, as assessed by the investigator.
• Cardiac troponin T or N-terminal pro-brain natriuretic peptide (NT-proBNP) levels out of normal range at screening.
• Positive pre-study drug/alcohol screen.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular use of known drugs of abuse.
• Estimated glomerular filtration rate (eGFR) of <90 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) or serum creatinine >1.5 times ULN or urine albumin:creatinine ratio of >300 mg per gram (g) at screening.
• Positive Severe acute respiratory syndrome- Coronavirus-2 (SARS-CoV-2) Polymerase chain reaction (PCR) or rapid antigen test at screening. Participants may be re-screened once they present a negative SARS-CoV-2 PCR or rapid antigen test.
• Participants with known Coronavirus Disease-2019 (COVID-19 positive contacts in the past 14 days.
• Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Smoker, smoking history or use of tobacco- or nicotine-containing products (for example, nicotine patches or vaporizing devices) within 6 months prior to screening.
• Sensitivity to heparin or heparin-induced thrombocytopenia.
• 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.

IPD for this study will be made available via the Clinical Study Data Request site.

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

All-cause mortality, serious adverse events (SAEs), and non-serious adverse events (non-SAEs) were collected up to 302 days

All-cause mortality, SAEs and non-SAEs were collected for the Safety Population that comprised of all randomized participants who received at least one dose of study treatment. Adverse events were presented treatment-wise.