A Study to Investigate the Safety of GSK4024484 in Healthy Adult Participants

A Phase 1, Randomised, Double Blind Placebo-controlled, First Time in Human Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Oral Doses and Food Effect of GSK4024484 in Healthy Adult Participants.

The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range, and the effect of food on the study intervention.

Study Overview

• Status: Recruiting
• Conditions: Malaria, Falciparum
• Intervention / Treatment: Drug: GSK4024484C; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0GG
    • Recruiting
    • GSK Investigational Site
    • Principal Investigator: Edward Banham-Hall
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
2. Participants who are considered healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac assessment.
3. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, or outside the normal reference range for the population being studied, may be included only if the Investigator considers, that the finding is unlikely to introduce additional risk factors for the participant and will not interfere with the study procedures or endpoints.
4. ALT (Alanine transaminase) and AST (Aspartate transaminase) within the normal range at screening.
5. Total bilirubin within the normal range unless the participant is known to have Gilbert's syndrome.
6. Body weight ≥50kg, and BMI within the range 19 to 32 kilogram per square metre (kg/m^2) inclusive.
7. Male participants and female participants who are not of child bearing potential.
8. The participant is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

1. History or presence of cardiovascular (including hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders, capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data in the opinion of the investigator.
2. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
3. An average weekly alcohol intake of >14 units a week within 6 months prior to the study. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
4. QTcF (Fridericia's formula) >450 msec based on average of triplicate ECGs. The QTcF is the QT interval corrected for heart rate according to QTcF.
5. More than 100 ventricular ectopic complexes in 24 hrs by Holter screening or any other clinically significant Holter abnormalities determined by the investigator.
6. Presence or history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
7. Heart rate <40 or >100 beats per minute (bpm).
8. Evidence of previous myocardial infarction or any clinically significant conduction abnormality such as (including but not specific to left complete bundle branch block, AV block [2nd degree or higher], WPW syndrome). Long standing RBBB is permitted.
9. Past or intended use of over-the-counter or prescription medication, including herbal medications, CBD-based products, PPIs or H2 antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing. Other concomitant medication may be considered on a case by case basis by the investigator in consultation with the medical monitor. Paracetamol is permitted (capped at ≤2 grams/day).
10. Participation in the study that would result in loss of blood or blood products in excess of 500 mL within a 56-day period.
11. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
12. Current enrolment or past participation (within the last 30 days before planned first dose in this study) in any other clinical study involving an investigational study intervention or any other type of medical research.
13. Participants previously dosed in this study.
14. Presence of HBsAg [or HBcAb] at screening or within 3 months prior to first dose of study intervention.
15. Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
16. Positive hepatitis C RNA (ribonucleic acid) test result at screening or within 3 months prior to first dose of study intervention.
17. Positive pre-study drug/alcohol screen.
18. Positive HIV antibody test.
19. Carbon monoxide levels indicative of smoking or more than 10 pack year history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
20. Use of known recreational drugs or drugs of abuse.
21. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.
22. A positive confirmation of COVID-19 infection according to local procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 6 mg single ascending dose (SAD) Group; Participants receive a 6 mg single dose of GSK4024484, in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 12 mg SAD Group; Participants receive a 12 mg single dose of GSK4024484 in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 24 mg SAD Group; Participants receive a 24 mg single dose of GSK4024484 in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 48 mg SAD Group; Participants receive a 48 mg single dose of GSK4024484 in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 96 mg SAD Group; Participants receive a 96 mg single dose of GSK4024484 in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 192 mg SAD Group; Participants receive a 192 mg single dose of GSK4024484, in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: Food Effect Group; Participants receive a single study dose of GSK4024484 in a fed state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 300 mg SAD Group; Participants receive a 300 mg single dose of GSK4024484, in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 400 mg SAD Group; Participants receive a 400 mg single dose of GSK4024484, in a fasted state.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: Optional SAD Group; Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Placebo Comparator: Placebo SAD Group; Participants receive placebo in a fed or fasted state.	Drug: Placebo; Doses administrated orally with 240 mL of water.
Experimental: 150 mg multiple ascending doses (MAD) Group; Participants receive 150 mg per day of GSK4024484 during 3 subsequent days (450 mg total).	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: 300 mg MAD Group; Participants receive 300 mg per day of GSK4024484 during 3 subsequent days (900 mg total).	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Experimental: Optional MAD Group; Participants may be included in this group, to allow flexibility if the dose escalation needs modification or a dose level needs to be added or repeated.	Drug: GSK4024484C; Doses administrated orally with 240 mL of water.
Placebo Comparator: Placebo MAD Group; Participants receive placebo during 3 subsequent days.	Drug: Placebo; Doses administrated orally with 240 mL of water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants reporting serious adverse events (SAEs) after single ascending doses	An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.	From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)
Percentage of participants reporting SAEs by severity after single ascending doses	Mild SAE = a type of adverse event (AE) that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.	From the signing of the informed consent (Day -2) until the follow up contact (Day 38 +/- 3 days post dose)
Percentage of participants reporting SAEs after multiple ascending doses	An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant or an abnormal partner pregnancy outcome.	From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)
Percentage of participants reporting SAEs by severity after multiple ascending doses	Mild SAE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate SAE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe SAE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.	From the signing of the informed consent (Day -2) until the follow up contact (Day 40 +/- 3 days post dose)
Percentage of participants reporting non-serious AEs after single ascending doses	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)
Percentage of participants reporting non-serious AEs by severity after single ascending doses	Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.	From study dose administration (Day 1) until the follow up contact (Day 38 +/- 3 days post dose)
Percentage of participants reporting non-serious AEs after multiple ascending doses	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.	From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)
Percentage of participants reporting non-serious AEs by severity after multiple ascending doses	Mild AE = a type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate AE = a type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the research participant. Severe AE = a type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.	From first study dose administration (Day 1) until the follow up contact (Day 40 +/- 3 days post dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A: Area under the plasma drug concentration versus time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC(0-t)] of GSK4024484C following single ascending doses in fasting conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Area under the plasma drug concentration versus time curve from zero (pre-dose) extrapolated to infinite time [AUC(0-∞)] of GSK4024484C following single ascending doses in fasting conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Maximum observed plasma drug concentration (Cmax) of GSK4024484C following single ascending doses in fasting conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK4024484C following single ascending doses in fasting conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Apparent terminal half-life (t1/2) of GSK4024484C following single ascending doses in fasting conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part B: AUC(0-t) of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: AUC(0-∞) of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: Cmax of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: Tmax of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: t1/2 of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: Area under the plasma drug concentration versus time curve from zero to time of trough plasma concentration [AUC(0-tau)] of GSK4024484C following multiple ascending doses in fasting conditions	Part B: From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part B: Trough plasma concentration (Ctau) of GSK4024484C following multiple ascending doses in fasting conditions	From first study dose administration (Day 1) until the follow up contact (Day 33 +/- 1 day post dose)
Part A: AUC(0-t) of GSK4024484C following single ascending doses in fed conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: AUC(0-∞) of GSK4024484C following single ascending doses in fed conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Cmax of GSK4024484C following single ascending doses in fed conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: Tmax of GSK4024484C following single ascending doses in fed conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part A: t1/2 of GSK4024484C following single ascending doses in fed conditions	From study dose administration (Day 1) until the follow up contact (Day 29 +/- 1 day post dose)
Part B: Observed accumulation ratio (R) of GSK4024484 based on AUC(Ro) following multiple ascending doses	At Day 1 and at Day 3
Part B: Observed accumulation ratio (R) of GSK4024484 based on Cmax(RCmax) following multiple ascending doses	At Day 1 and at Day 3

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Medicines for Malaria Venture

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): August 7, 2026
• Study Completion (Estimated): August 7, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Food effect; Healthy adults; First time in human; Multiple oral doses; GSK4024484; Single oral doses
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum
• Other Study ID Numbers: 218708

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://d3l8i7lo48obsd.cloudfront.net/gsk-patient-level-data-sharing-july2025-1-Bgwa1UthxvluYbWYTThw.pdf
• 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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No