A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Oral GSK4172239D Compared With Placebo in Sickle Cell Disease Participants Aged 18 to 50 Years

Inclusion criteria:

• Participants diagnosed with SCD not taking medication which increases gamma-globin (fetal hemoglobin).

• Participants with SCD who have failed or not tolerated one or more approvedtherapies for SCD

• Body weight greater than (>) 50 kilogram (kg).

• For male participants: Refrain from donating sperm plus either be abstinent fromheterosexual intercourse as their preferred and usual lifestyle (abstinent on a longterm and persistent basis) and agree to remain abstinent. OR agree to use a malecondom with female partner. Agree to use an additional highly effectivecontraceptive method with a failure rate of less than (<) 1% per year when havingsexual intercourse with a woman of childbearing potential who is not currentlypregnant

• For female participants: Female participants are eligible to participate if they area woman of non-childbearing potential (WONCBP).

• Capable of giving informed consent.

Exclusion Criteria:

• Presence of active, clinically significant cardiovascular, respiratory, hepatic,renal, gastrointestinal, endocrine, or neurological disorders capable ofsignificantly altering the absorption, metabolism, or elimination of drugs;constituting a risk when taking the study drug; or interfering with theinterpretation of data.

• Clinically significant abnormal blood pressure and/or history of hypertension asdetermined by the investigator.

• History of clinically significant heart disease as determined by the investigator.

• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m^2

• ALT > 3x upper limit of normal (ULN).

• Bilirubin > 5x ULN (isolated bilirubin > 5x ULN is acceptable if bilirubin isfractionated and direct bilirubin <35%).

• Hemoglobin < 6 gram/decalitre (g/dL).

• Absolute neutrophil count <1,500 / microlitre (μL).

• Platelet count <75,000 /μL or >750,000 /μL.

• Use of prescription or non-prescription drugs, including vitamins, herbal anddietary supplements (including St John's Wort) within 7 days (or 14 days if the drugis a potential enzyme inducer) or 5 t1/2 (whichever is longer) prior to the firstdose of study drug, unless in the opinion of the Investigator and GSK MedicalMonitor the medication will not interfere with the study procedures or compromiseparticipant safety. By exception, participant may take acetaminophen (less than orequal to [≤] 2 g/day) up to 48h prior to the first dose of study drug.

• Use of hydroxyurea or decitabine within 9 weeks prior to baseline through follow-up.

• Blood transfusion within 3 months prior to baseline through follow-up.

• Current enrollment or past participation within the last 30 days before signing ofconsent in this or any other clinical study involving an investigational study drugor any other type of medical research.

• Positive pre-study drug/alcohol screen. By exception, opioid use for pain orbenzodiazepine use for anxiety as directed by a physician is permitted.

• Regular use of known drugs of abuse, except for use directed by a physician. Byexception, opioid use for pain or benzodiazepine use for anxiety is permitted.