Last updated: 09/21/2026 07:01:30
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
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
Official title: 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
Trial description: This was a first-time-in-human (FTIH) study in participants with sickle cell disease (SCD). The study was planned to evaluate the safety, tolerability, and pharmacokinetics of GSK4172239D. The study consisted of Screening, Treatment, and Follow-up periods. Participants were randomized to receive either GSK4172239D or placebo prior to first dosing on Day 1. GSK4172239D is a prodrug that is converted in vivo to GSK4106401. The study was designed as a single-dose, dose-escalation study with staggered sentinel dosing. One selected cohort of participants was also planned to receive a single dose of GSK4172239D (or matching placebo) under fed conditions (high calorie and high fat) to assess the food effect. The study was originally planned to include five sequential cohorts. Following completion of Cohort 1 and partial completion of Cohort 2, the study was terminated for strategic business reasons unrelated to participant safety. Consequently, Cohorts 3, 4, and 5 were not initiated and no participants were enrolled in those cohorts.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Allocation:
Randomized
Primary outcomes:
Area under curve zero to time infinity (AUC 0-inf) for Metabolite GSK4106401 after a single oral dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Maximum observed plasma concentration (Cmax) for Metabolite GSK4106401 after a single oral dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Time to Cmax (Tmax) for Metabolite GSK4106401 after a single oral dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Apparent terminal Half-life (t1/2) for Metabolite GSK4106401 after a single oral dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Ratio between the fed and fasted conditions for AUC (0-inf) of Metabolite GSK4106401 after a Single Oral Dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Ratio between the fed and fasted conditions for Cmax of Metabolite GSK4106401 after a Single Oral Dose of GSK4172239D
Timeframe: Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 4h, 6h, 8h, 12h, 18h, 24h, 36h, 48h
Secondary outcomes:
Number of participants with clinically significant changes in Hematology Parameters
Timeframe: From Baseline up to Day 7
Number of participants with clinically significant changes in Chemistry Parameters
Timeframe: From Baseline up to Day 7
Number of participants with adverse event (AE) and serious adverse event (SAE)
Timeframe: Up to Day 7
Number of participants with clinically significant changes in 12 lead electrocardiograms (ECG) Findings
Timeframe: From Baseline up to Day 7
Number of participants with clinically significant changes in vital signs findings
Timeframe: From Baseline up to Day 7
Interventions:
Drug: GSK4172239D
Other: Placebo
Enrollment:
11
Primary completion date:
2025-22-09
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hematologic Diseases
Product
Not applicable
Collaborators
Not applicable
Study date(s)
August 2023 to September 2025
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 50 Years
Accepts healthy volunteers
No
- 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
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Raleigh, North Carolina, United States, 27617
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Las Vegas, NV, United States, 89113-2235
Status
Study Complete
Location
GSK Investigational Site
Greenville, NC, United States, 27834
Status
Terminated/Withdrawn
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2025-22-09
Actual study completion date
2025-22-09
Plain language summaries
Summary of results in plain language
Available language(s): English, Spanish (United States)
Additional information about the trial
Additional information
Not applicable
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