A Safety, Tolerability, Pharmacokinetics (PK) and Target Engagement (TE) Study of GSK3858279 in Healthy Participants and Evaluation of the Efficacy of Repeat Doses in Participants With Osteoarthritis (OA)

Inclusion Criteria

For Part A:

• Participants between 18 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.
• Body weight within the range 50 to 100 kilogram (kg) and body mass index (BMI) within the range 18 to 32 kilogram per meter square (kg/m^2) (inclusive).
• 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.

For Part B:

• Age between 40 and 75 years of age inclusive, at the time of signing the informed consent.
• OA of the index knee as defined by symptomatic for >=6 months with a clinical diagnosis of OA as per American College of Rheumatology (ACR) clinical diagnosis criteria.
• Average of daily pain score >=4 and =2 on X-ray obtained during screening. In addition, for participants with bilateral Knee OA, the index knee is determined at Baseline as the participant reported most painful knee over the 4 weeks prior to Baseline.
• A history of insufficient pain relief from, or inability to tolerate, or contraindication to, oral Non-steroidal anti-inflammatory drugs (NSAIDs).
• A participant must be willing and able to understand and participate in all scheduled evaluations and to complete all required tests and procedures including the use of patient diaries. This will be judged by the Investigator during the screening period.
• BMI within the range 19-34.9 kg/m^2 (inclusive)
• 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 or homosexual 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: 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

For Part A:

• History or presence of 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 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 GlaxoSmithKline (GSK) medical monitor's judgments.
• History or evidence of clinically significant multiple or severe drug allergies, intoleranc