Investigating a new oral medication for sickle cell disease

A Randomized, Placebo-controlled, Double-Blind (Sponsor Unblind), Parallel Group, Single Dose, Dose Escalation Phase I Study in Sickle Cell Disease Participants, to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK4172239D

This study is testing a new oral medication for sickle cell disease to see if it's safe and how well it works for adults aged 18 to 50.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: GlaxoSmithKline (industry)
• Locations: 8 sites (Miami, Florida and 7 other locations)
• Trial ID: NCT05660265 on ClinicalTrials.gov

What this trial studies

This clinical trial is a first-time-in-human study aimed at evaluating the safety, tolerability, and pharmacokinetics of GSK4172239D in participants with sickle cell disease aged 18 to 50 years. The study consists of three periods: screening, treatment, and follow-up, where participants will be randomized to receive either the investigational drug or a placebo. The trial will involve a single dose, dose-escalation approach, with initial dosing staggered to ensure safety. Participants will also undergo additional dosing under specific conditions after a washout period.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 50 with a diagnosis of sickle cell disease who have not responded to or tolerated existing therapies.

Not a fit: Patients currently taking medications that increase gamma-globin levels or those with active, clinically significant conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a new treatment option for patients with sickle cell disease.

How similar studies have performed: While this is a first-time-in-human study, similar approaches in developing treatments for sickle cell disease have shown promise in other trials.

Eligibility criteria

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 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.

Exclusion Criteria:

* 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/1.73m\^2
* 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.

Where this trial is running

Miami, Florida and 7 other locations

• GSK Investigational Site — Miami, Florida, United States (RECRUITING)
• GSK Investigational Site — Miami, Florida, United States (RECRUITING)
• GSK Investigational Site — Tamarac, Florida, United States (RECRUITING)
• GSK Investigational Site — Atlanta, Georgia, United States (RECRUITING)
• GSK Investigational Site — Columbus, Georgia, United States (RECRUITING)
• GSK Investigational Site — Riverdale, Georgia, United States (RECRUITING)
• GSK Investigational Site — Las Vegas, Nevada, United States (RECRUITING)
• GSK Investigational Site — Raleigh, North Carolina, United States (WITHDRAWN)

Study contacts

• Study coordinator: US GSK Clinical Trials Call Center

Conditions: Hematologic Diseases, Anaemia, Sickle Cell, Hematologic diseases, Sickle cell disease, First time in human study, 218471