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

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 will be a first time in human (FTIH) study in sickle cell diseases (SCD) participants. The FTIH study is planned to evaluate the safety, tolerability, and pharmacokinetics of GSK4172239D.

The study will be composed of 3 periods for all participants (Screening, Treatment, and Follow up). Participants will be screened and, prior to first dose on Day 1, will be randomized to receive either GSK4172239D or placebo.

GSK4172239D is a prodrug that is converted in vivo into GSK4106401. This study will be a single dose, dose-escalation study. The initial dosing for all cohorts will be staggered so that 2 participants will be dosed as sentinel participants. Provided there are no safety concerns in 48 hours (h), the remaining 6 participants scheduled for the cohort may be dosed. One selected cohort of participants will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions after a washout period of a minimum of 20 days or 5 half-lives, whichever is longer, designated as the Food Effect Cohort.

Study Overview

• Status: Terminated
• Conditions: Hematologic Diseases; Anaemia, Sickle Cell
• Intervention / Treatment: Other: Placebo; Drug: GSK4172239D

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33155
      • GSK Investigational Site
    • Tamarac, Florida, United States, 33321
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30315
      • GSK Investigational Site
    • Columbus, Georgia, United States, 31904
      • GSK Investigational Site
    • Riverdale, Georgia, United States, 30274
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.
Experimental: Cohort 2; Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.
Experimental: Cohort 3; Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.
Experimental: Cohort 4; Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.
Experimental: Cohort 5; Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.
Experimental: Food effect cohort; One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.	Other: Placebo; Matching placebo will be administered.; Drug: GSK4172239D; Different strength of GSK4172239D will be administered in different cohorts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D	Up to Day 3
Maximum observed plasma concentration (Cmax) for GSK4106401 after a single oral dose of GSK4172239D	Up to Day 3
Time to Cmax (Tmax) for GSK4106401 after a single oral dose of GSK4172239D	Up to Day 3
Half-life (t1/2) for GSK4106401 after a single oral dose of GSK4172239D	Up to Day 3
Ratio between the fed and fasted conditions for AUC (0-inf)	Up to Day 3
Ratio between the fed and fasted conditions for Cmax	Up to Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with clinically significant changes from baseline in white blood cell (WBC)	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in hemoglobin	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in platelets count	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in neutrophil count	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in alanine transaminase (ALT)	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in aspartate transaminase (AST)	Baseline and up to Day 7
Number of participants with clinically significant changes from baseline in bilirubin	Baseline and up to Day 7
Number of participants with adverse event (AE) and serious adverse event (SAE)	Up to Day 7
Number of participants with clinically significant change from baseline in 12 lead electrocardiograms (ECG)	Baseline and up to Day 7
Number of participants with clinically significant change from baseline in vital signs	Baseline and up to Day 7

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2023
• Primary Completion (Actual): September 22, 2025
• Study Completion (Actual): September 22, 2025

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Sickle cell disease; Hematologic diseases; First time in human study; 218471
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Hematologic Diseases
• Other Study ID Numbers: 218471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No