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

Open to people ages 18-50

• 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 approved therapies for SCD
• Body weight greater than (>) 50 kilogram (kg).
• For male participants: 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 agree to use a male condom with female partner. Agree to use an additional highly effective contraceptive method with a failure rate of less than (<) 1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
• For female participants: Female participants are eligible to participate if they are a woman of non-childbearing potential (WONCBP).
• Capable of giving informed consent.

• Presence of active, clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug; or interfering with the interpretation of data.
• Clinically significant abnormal blood pressure and/or history of hypertension as determined by the investigator.
• History of clinically significant heart disease as determined by the investigator.
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m²
• ALT > 3x upper limit of normal (ULN).
• Bilirubin > 5x ULN (isolated bilirubin > 5x ULN is acceptable if bilirubin is fractionated 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 and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 t1/2 (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, participant may take acetaminophen (less than or equal 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 of consent in this or any other clinical study involving an investigational study drug or any other type of medical research.
• Positive pre-study drug/alcohol screen. By exception, opioid use for pain or benzodiazepine use for anxiety as directed by a physician is permitted.
• Regular use of known drugs of abuse, except for use directed by a physician. By exception, opioid use for pain or benzodiazepine use for anxiety is permitted.