A randomized, double-blind, placebo-controlled, three-period two treatment incomplete-block crossover study to investigate the effects of intravenous GSK3858279 on a battery of evoked pain tests in healthy participants.

1. Participant must be 18 to 50 years of age inclusive, at the time of signing
the informed consent.
2. Participants who are overtly healthy as determined by medical evaluation
including medical history, physical examination, laboratory tests, vital signs
and cardiac monitoring.
3. Body weight within 50*100 kg and body mass index (BMI) within the range
18---30 kg/m2 (inclusive).
4. Must be Male:
Participants must agree to the following during the intervention period and for
at least 90 days after the last dose of study intervention:
- Refrain from donating sperm.
PLUS, either:
-Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle
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.
5. Capable of giving signed informed consent as described in Appendix 1 of the
protocol which includes compliance with the requirements and restrictions
listed in the informed consent form (ICF) and in this protocol.

1. History or presence of/significant history of or current 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
2. Personal or family history of cardiomyopathy.
3. Abnormal blood pressure as determined by the investigator.
4. Symptomatic herpes zoster within 3 months prior to screening.
5. Evidence of active or latent tuberculosis (TB) as documented by medical
history andvexamination, and TB testing: a positive (not indeterminate)
QuantiFERON-TB Gold test.
6. Significant allergies to humanized monoclonal antibodies.
7. 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)
8. Lymphoma, leukaemia, or any malignancy. Those who are at risk of DNA repair
diseases or any family history of DNA repair disease.
9. Alanine transaminase (ALT) >1.5x upper limit of normal (ULN).
10. Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin <35%).
11. Current or chronic history of liver disease or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).
12. QTc >450 msec
NOTES:
-The QTc is the QT interval corrected for heart rate according to Bazett*s
formula (QTcB), Fridericia*s formula (QTcF), and/or another method, machineread
or manually over-read.
- The specific formula that will be used to determine eligibility and
discontinuation for an individual subject will be QTcF. In other words, several
different formulae cannot be used to calculate the QTc for an individual subject
and then the lowest QTc value used to include or discontinue the subject from
the trial.
-For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a
composite of available values of QTc will be used as specified in the Reporting
and Analysis Plan (RAP).
13. History of Stevens-Johnson Syndrome.
14. Known immunodeficiency.
15. Participants with an acute, re-current or chronic infection (e.g.,
osteomyelitis), who have been receiving treatment within three months prior to
dosing or individuals with an active infection.
16. Previous or current history of excessive bleeding or coagulation disorders.
17. Previous history of hypertrophic or keloid scarring.
18. 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, hypothyroidism) or pain (such as
disease that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia,
neuropathy).
19. 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 PI judgement.
20. History or presence of post-inflammatory hyperpigmentation. Applicable for
the participants in the UVB-MITT population only.
21. Participants with Fitzpatrick skin type IV, V or VI. Applicable for the
participants in the UVB-MITT population only.
22. 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.
23. A minimal erythema dose (MED) higher than 355 mJ/cm2 at screening.
Applicable for the participants in the UVB-MITT population only.
24. Past or intended use of over-the-counter or prescription medication
including herbal medications within 7 days prior to dosing until after
follow-up visit.
25. Live vaccine(s) within 1 month prior to dosing or plans to receive such
vaccines during the study.
26. 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.
27. Treatment with anti-platelet or anti-coagulant agents within 7 days of
dosing.
28. Major surgery (as per investigator*s judgement) within 3 months prior to
dosing.
29. Participant has made a blood or plasma donation or has had a comparable
blood loss
(>450mL) within the last 3 months prior to the Screening Visit. Blood donation
during the study is not permitted.
30. Exposure to more than 4 new chemical entities within 12 months prior to the
first dosing day.
31. Current enrolment 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 dosing in this current study.
32. Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3
months prior to first dose of study intervention.
33. Presence of Hepatitis B core antibody (HbcAb) at screening or within 3
months prior to first dose of study intervention.
34. Positive Hepatitis C antibody test result at screening or within 3 months
prior to first dose of study intervention.
NOTE: Subjects with positive Hepatitis C antibody due to prior resolved disease
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is
obtained
35. Positive Hepatitis C RNA test result at screening or within 3 months prior
to first dose of study intervention. NOTE: Test is optional and subjects with
negative Hepatitis C antibody test are not required to also undergo Hepatitis C
RNA testing
36. Abnormal clinically significant echocardiogram at screening, as assessed by
the investigator.
37. Cardiac troponin T or NT-proBNP levels out of normal range at screening.
38. Positive pre-study drug/alcohol screen.
39. Positive human immunodeficiency virus (HIV) antibody test.
40. Regular use of known drugs of abuse.
41. Estimated glomerular filtration rate (eGFR) of <90 mL/min/1.73 m2 or serum
creatinine >1.5xULN or urine albumin:creatinine ratio of >300mg/g at screening.
42. Positive SARS-CoV-2 PCR test at screening. Participants may be re-screened
once they present a negative SARS-CoV-2 PCR.
43. Subjects with known COVID-19 positive contacts in the past 14 days
44. 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 (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL)
measure of spirits.
45. Smoker, smoking history or use of tobacco- or nicotine-containing products
(e.g. nicotine patches or vaporizing devices) within 6 months prior to
screening.
46. Sensitivity to heparin or heparin-induced thrombocytopenia.
47. 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.